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Journal articles on the topic 'Polyclonal gammopathy'

Author: Grafiati

Published: 7 June 2025

Last updated: 26 June 2025

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1

Lee, Dae Kyu, Dong Gyu Kim, Gheeyoung Choe, Je G. Chi, and Hee-Won Jung. "Chordoid meningioma with polyclonal gammopathy." Journal of Neurosurgery 94, no. 1 (2001): 122–26. http://dx.doi.org/10.3171/jns.2001.94.1.0122.

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✓ The authors present a case of chordoid meningioma in a 55-year-old woman who manifested headache and personality change. Magnetic resonance imaging of the brain and cerebral angiography demonstrated a mass in the right frontal lobe that resembled a typical convexity meningioma. However, the pathological diagnosis was chordoid meningioma, a rare subtype of this tumor that usually occurs in adolescence and is known to be associated with Castleman syndrome. A meningothelial meningiomatous pattern suggestive of a meningothelial origin was focally present, and cytokeratin-positive squamoid cells were noted in the tumor. The lesion lacked dense infiltration of lymphocytes and plasma cells. Polyclonal gammopathy was the only sign of Castleman syndrome and hypochromic microcytic anemia was absent in this case. Polyclonal gammopathy resolved completely 6 months after total removal of the mass.

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Kim, Yong Bang, Si-Hoon Lee, and Joong-Seok Kim. "Chlorpromazine-induced Parkinsonism and Polyclonal Gammopathy." Korean Journal of Clinical Geriatrics 17, no. 1 (2016): 39–41. http://dx.doi.org/10.15656/kjcg.2016.17.1.39.

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3

Gorson, K. C., A. H. Ropper, A. K. Palmetshofer, and R. Weinstein. "Prevalence of polyclonal gammopathy in polyneuropathy." Neurology 49, no. 6 (1997): 1747. http://dx.doi.org/10.1212/wnl.49.6.1747.

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4

Leung, Nelson. "My Patient with Monoclonal Gammopathy of Undetermined Significance has a Kidney Problem." Journal of Onco-Nephrology 1, no. 1 (2017): 18–23. http://dx.doi.org/10.5301/jo-n.5000005.

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Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition signifying the presence of a B-cell lymphoproliferative disorder. By connotation, it should not meet the definition of multiple myeloma, Waldenström macroglobulinemia, or lymphoma. In addition, it cannot be responsible for any end-organ damage. Similar to polyclonal immunoglobulins (Ig), monoclonal gammopathy has been increasingly recognized as an important cause of kidney disease. The recent introduction of the term “monoclonal gammopathy of renal significance” (MGRS) highlights this importance. MGRS is similar to MGUS in which the B-cell lymphoproliferative disorder has not reached a state considered to be malignant, but differentiates itself by the presence of a monoclonal gammopathy related kidney disease. This distinction is important since it separates MGRS, which is not benign, from the MGUS condition, which is benign. It also allows for a better classification of kidney diseases caused by monoclonal gammopathies. There are many renal diseases and lesions that have been identified to be secondary to MGRS. In addition, MGRS-associated renal diseases can mimic polyclonal Ig mediated kidney diseases. Kidney biopsy with immunofluorescence is the key for diagnosing MGRS-related kidney diseases. Once the diagnosis is made, a specific evaluation is needed for the diagnosis and treatment of MGRS-related kidney diseases that differs from the polyclonal Ig counterparts.

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Vladutiu, A. O., B. M. Roach, and S. M. Farahmand. "Polyclonal gammopathy with marked increase in serum viscosity." Clinical Chemistry 37, no. 10 (1991): 1788–93. http://dx.doi.org/10.1093/clinchem/37.10.1788.

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Abstract A 45-year-old man with polyclonal hypergammaglobulinemia (gamma globulins, 102 g/L) had a serum relative viscosity of 13 nu but did not manifest clinical signs of hyperviscosity syndrome (e.g., retinopathy, bleeding diathesis, and neurological alterations), except for fatigue and anorexia. In contrast with other patients with polyclonal hyperviscosity reported so far, this patient did not have detectable rheumatoid factor in serum. Analytical ultracentrifugation of his serum showed aggregates of polyclonal IgG3 of various sizes (between 10 and 36 S). The serum also contained immune complex-like material, as demonstrated by the Raji cell immunoradiometric assay and the C1q solid-phase enzyme immunoassay.

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Wu, M.-T., C.-H. Chang, H.-S. Yu, and J.-S. Bair. "Scleromyxoedema with prominent linear eruption and polyclonal gammopathy." Clinical and Experimental Dermatology 22, no. 2 (1997): 110–11. http://dx.doi.org/10.1111/j.1365-2230.1997.tb02637.x.

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7

Gookin, Jody L., Ranee K. Sellon, Kevin S. McDorman, and Frank J. Geoly. "Systemic Plasmacytosis and Polyclonal Gammopathy in a Dog." Journal of Veterinary Internal Medicine 12, no. 6 (1998): 471–74. http://dx.doi.org/10.1111/j.1939-1676.1998.tb02152.x.

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8

Zamarin, Dmitriy, Maria Arcila, Sergio A. Giralt, et al. "Polyclonal IgA Gammopathy Associated with Polyclonal Plasmacytosis in Patients Receiving Lenalidomide Maintenance Therapy." Blood 118, no. 21 (2011): 5130. http://dx.doi.org/10.1182/blood.v118.21.5130.5130.

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Abstract Abstract 5130 INTRODUCTION: Lenalidomide is commonly used in the treatment of multiple myeloma both in the upfront and relapsed settings and appears to also yield promising results as maintenance therapy after autologous stem cell transplantation. The immunomodulatory mechanisms of action of lenalidomide are complex and the side effects of long-term therapy are still not fully known. Here we report a series of patients on lenalidomide maintenance therapy who demonstrated significant elevation of serum polyclonal immunoglobulin A (IgA) levels with associated polyclonal plasmacytosis in the absence of disease progression. METHODS AND RESULTS: We identified 6 patients who, in the course of lenalidomide maintenance therapy, were noted to have asymptomatic elevation of serum IgA levels above normal limits without evidence of monoclonality by immunofixation of serum protein electrophoresis. The original myeloma-associated monoclonal protein was IgG kappa in 5 patients and IgG lambda in 1 patient. Two patients received lenalidomide as part of their induction regimen prior to autologous stem cell transplantation, and transient elevation of IgA level was noted at that time. None of the patients had evidence of IgA gammopathy prior to initiation of lenalidomide. Mean time from initiation of lenalidomide maintenance therapy to elevation of IgA level was 9.8 months (range 2 to 22 months). The mean highest IgA level reached for the 6 patients was 534 mg/dl (range 520 to 1190 mg/dl). Bone marrow aspirate and biopsy were available in 3 patients during the period of IgA elevation. The plasma cell population accounted for 9%, 12% and 20% of the bone marrow nucleated cells on the aspirate. Immunohistochemical staining (HIS) of the bone marrow biopsy showed a moderate increase in the number of CD138 positive plasma cells without light chain restriction. HIS using IgA antibody revealed that the plasma cells were mostly IgA producing. None of the 6 patients had any evidence of progression of their original myeloma-associated paraprotein in the setting of polyclonal IgA elevation. Five patients continue to receive lenalidomide maintenance to date (treatment time length ranging between 17.3 and 43.4 months) with no evidence of serologic or clinical disease progression and with persistently elevated IgA levels. One patient discontinued lenalidomide therapy secondary to development of neuropathy with subsequent normalization of IgA level 21 months later. CONCLUSIONS: Polyclonal IgA gammopathy associated with polyclonal IgA-producing plasmacytosis can occur with lenalidomide maintenance and perhaps lenalidomide treatment. The immunologic basis and implication of this observation is unknown. Awareness of this effect is important especially in view of the associated significant bone marrow plasmacytosis, which may mistakenly be construed as disease relapse or progression in patients who are actually responding to treatment. Disclosures: No relevant conflicts of interest to declare.

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9

Dispenzieri, Angela, Morie A. Gertz, Terry M. Therneau, and Robert A. Kyle. "Retrospective cohort study of 148 patients with polyclonal gammopathy." Mayo Clinic Proceedings 76, no. 5 (2001): 476–87. http://dx.doi.org/10.4065/76.5.476.

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10

Talamo, Giampaolo, Marcelle G. Meseeha, Muneer Khan, Julie L. Richards, Shobha Mandal, and Joyson Poulose. "Clinical Conditions Associated with Elevated Serum Levels of Polyclonal Free Light Chains." Guthrie Journal 76, no. 2 (2025): 64–70. https://doi.org/10.3138/guthrie-2024-0009.

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Background: Polyclonal gammopathy with elevation of the intact immunoglobulin (Ig) molecules is a laboratory finding commonly observed in a variety of inflammatory disorders, such as infections, autoimmune diseases, and cancer. Little is known about the relative frequency of the conditions associated to the serum elevation of polyclonal free light chains (FLCs). Methods: We reviewed laboratory data and clinical features of 62 patients who were referred to our Hematology/Oncology clinic due to elevated Ig or serum FLCs, and for whom the work-up ruled out the presence of a clonal plasma cell dyscrasia or a hematologic malignancy. Results: Serum elevation of the polyclonal intact Ig, FLCs, or both, was observed in 8 (13%), 30 (48%), and 24 (39%) patients, respectively. The causes of elevated Ig, either alone or in combination with elevated FLCs, were connective tissue diseases (12 cases), autoimmune diseases (6 cases), infections (5 cases), and various other chronic diseases (10 cases). Among the 30 patients with isolated elevation of FLCs, an inflammatory disease was present in 5 cases, and 22 patients (73%) had either acute or chronic kidney disease. In these patients, we found a correlation between FLC level and glomerular filtration rate (GFR): r was −0.61 ( P = 0.003) and −0.49 ( P = 0.021) for kappa and lambda FLCs, respectively. Conclusion: Serum elevation of polyclonal FLCs can be due to either overproduction, associated with various infectious and inflammatory disorders, or underexcretion, related to chronic renal insufficiency. We believe that a term such as polyclonal lightchainemia could be used to indicate the laboratory finding of elevated FLCs in the absence of a clonal hematologic dyscrasia. This should be distinguished from the traditional terms hypergammaglobulinemia and polyclonal gammopathy, which instead refer to the elevation of all Ig molecules.

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Conrad, Marcel E., and Lydia F. Latour. "Acquired von willebrand's disease, IgE polyclonal gammopathy and griseofulvin therapy." American Journal of Hematology 41, no. 2 (1992): 143. http://dx.doi.org/10.1002/ajh.2830410218.

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Puranik, Shaila C., Kalpana B. Rathod, and Jyoti K. Kudrimoti. "Toxoplasmosis Presenting as Hyper Viscosity Syndrome due to Polyclonal Gammopathy." Indian Journal of Hematology and Blood Transfusion 30, no. 1 (2012): 51–53. http://dx.doi.org/10.1007/s12288-012-0191-6.

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13

Young, Paul E., Heba Badr, and Anthony O. Okorodudu. "Persistent Unexplained Polyclonal IgA Gammopathy in a Patient with Multiple Myeloma." Clinical Chemistry 71, no. 2 (2025): 335–36. https://doi.org/10.1093/clinchem/hvae136.

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Cho, Eun-Mi, Hye-Hyun Moon, Young-Ju Hwang, Seung-Jin Lee, Cheol Woo Ko, and Min Hyun Cho. "Polyclonal gammopathy related to renal bleeding in a peritoneal dialysis patient." Korean Journal of Pediatrics 56, no. 7 (2013): 304. http://dx.doi.org/10.3345/kjp.2013.56.7.304.

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Endo, Kaoru, Naoki Suzuki, Taro Ikenishi, Masashi Aoki, and Yasuto Itoyama. "Intravenous Immunoglobulin Treatment Successfully Improved Subacute Progressive Polyradiculoneuropathy with Polyclonal Gammopathy." Internal Medicine 48, no. 23 (2009): 2037–39. http://dx.doi.org/10.2169/internalmedicine.48.2545.

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Baldini, L., A. Guffanti, BM Cesana, et al. "Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy." Blood 87, no. 3 (1996): 912–18. http://dx.doi.org/10.1182/blood.v87.3.912.bloodjournal873912.

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The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow- up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low- risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.

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Grados, Aurélie, Mikael Ebbo, José Boucraut, et al. "Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease." International Journal of Rheumatology 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/426759.

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Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that theκ() andλ() free light chains and theκ : λratio () are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase ofκandλfree light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

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McMaster, Mary L., Sigurdur Y. Kristinsson, Ingemar Turesson, Magnus Björkholm, and Ola Landgren. "Novel Aspects Pertaining to the Relationship of Waldenström's Macroglobulinemia, IgM Monoclonal Gammopathy of Undetermined Significance, Polyclonal Gammopathy, and Hypoglobulinemia." Clinical Lymphoma and Myeloma 9, no. 1 (2009): 19–22. http://dx.doi.org/10.3816/clm.2009.n.003.

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Bouzani, Maria, John Apostolidis, Dimitra Rondogianni, Nikolaos Harhalakis, Constantinos Tsatalas, and Emmanuel Nikiforakis. "Idiopathic Plasmacytic Lymphadenopathy with Polyclonal Gammopathy in a Patient of Western Origin." International Journal of Surgical Pathology 13, no. 1 (2005): 125–26. http://dx.doi.org/10.1177/106689690501300121.

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Sarnat, Richard L., and Lee M. Jampol. "Hyperviscosity Retinopathy Secondary to Polyclonal Gammopathy in a Patient with Rheumatoid Arthritis." Ophthalmology 93, no. 1 (1986): 124–27. http://dx.doi.org/10.1016/s0161-6420(86)33782-5.

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Beak, Eun Kyung, Sun Hee Roh, Jin Kyeong Park, et al. "A Case of C-ANCA Positive Rapidly Progressive Glomerulonephritis Associated with Polyclonal Gammopathy." Ewha Medical Journal 31, no. 1 (2008): 31. http://dx.doi.org/10.12771/emj.2008.31.1.31.

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Liu, Hui, Guojin Wang, Jia Song, Jing Guan, Zonghong Shao, and Rong Fu. "Pseudo-monoclonal gammopathy due to autoimmune disease: a case report." Journal of International Medical Research 48, no. 2 (2019): 030006051986661. http://dx.doi.org/10.1177/0300060519866618.

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Hyperglobulinemia is a common manifestation of plasma cell disease, and it is sometimes caused by autoimmune diseases (AIDs). We report an uncommon presentation of hyperglobulinemia, with a high amount of plasma cells in bone marrow, pancytopenia, hematemesis, and splenomegaly in an 18-year-old woman. Some examinations were performed to determine the diagnosis, including serum protein electrophoresis, immunofixation electrophoresis, the free light chain assay, abdominal enhanced computed tomography (CT) and CT venography, and positron-emission tomography-CT. The patient was finally diagnosed with AID. Considerable improvement in her symptoms was observed after immunosuppressive therapy. Findings in this case highlight that not only differentiation of hyperglobulinemia caused by monoclonal or polyclonal immunoglobulin, but also AIDs, need to be considered to exclude non-Hodgkin’s lymphoma and plasma cell disease.

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Greco, Antonino, Alessandra Trojani, Milena Lodola, Barbara Di Camillo, Alessandra Tedeschi, and Enrica Morra. "Gene Expression Profiling of IgM Monoclonal Gammopathy of Undetermined Significance (IgM-MGUS)." Blood 124, no. 21 (2014): 5187. http://dx.doi.org/10.1182/blood.v124.21.5187.5187.

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Abstract The 2nd IWWM tried to define reproducible criteria for the diagnosis of IgM-MGUS and Waldenstrom's Macroglobulinemia. IgM-MGUS was defined as asymptomatic condition characterized by serum IgM monoclonal protein (MC) without morphologic evidence of bone marrow (BM) lymphoplasmacytic infiltration. The proposal of the guidelines was to classify as MGUS also patients with equivocal evidence of BM infiltration, such as those presenting clonal B-cells by multiparameter flow cytometry (MFC) in the absence of morphologic evidence of BM infiltration, as well as those with equivocal BM infiltrates not confirmed by immunophenotypic studies. Patients The diagnosis of IgM-MGUS was made in 11 patients (6 males, 5 females) according to the consensus panel criteria. The median age at diagnosis was 73 (range, 60-77). Ten patients had K light chains. The median erythrocyte sedimentation rate was 11. The MC level at diagnosis ranged from 0.1 to 1.2 g/dL (median 0.4). Only one patient had MC value > 1.0 g/dL. The median IgM value was 697 mg/dL (range 116-1790). Five of 11 IgM-MGUS patients showed a small clonal B-cell population (light-chain-isotype-positive B-cells) detected by MFC without histologic evidence of BM infiltration. Therefore, patients were divided in 2 groups: group 1 (n=5) showing a clonal B-cell population, and group 2 (n=6) with polyclonal B-cells at MFC. Methods and results We isolated BM CD19+ cells in the 11 IgM-MGUS patients using Miltenyi Microbeads and performed microarray with Affymetrix-HG-U133 Plus 2.0 array. Gene set enrichment analysis (GSEA) was performed and different sets of genes were defined based on REACTOME pathways, KEGG pathways and GO Biological Process Terms. Interestingly, 17 top-ranking gene sets including differently expressed genes, reached a nominal p-value lower than 0.001; 2 gene sets were upregulated (while 15 gene sets were downregulated in monoclonal vs. polyclonal IgM-MGUS (table 1). No genes resulted significantly differentially expressed between group 1 and group 2 using a classic SAM test for microarrays and correcting for multiple testing with a false discovery rate (FDR) threshold of 5%. Similarly, IgM and MC were not differentially expressed between the two groups, although IgM showed a nominal p-value of 0.09 (t-test). However, when using linear regression to explain each gene expression data as a function of both IgM and MC, UBTF, TRIM5, FLJ35816, RDH10 genes were selected based on a FDR equal to 5%, applied to the F-statistic p-value. In particular, the model fitting UBTF had a p-value of 9.461e-07 and an adjusted R-squared of 0.9786; table 2 displays the coefficients of the model and the related p-values, showing a positive co-regulation of UBTF with MC. Conclusions In conclusion, microarray of IgM-MGUS gives insights into gene expression differences in IgM-MGUS. Notably, UBTF is a transcription factor which plays a crucial role in the transcription of rRNA in ERK-pathway, suggesting a possible role of ERK-pathway in IgM-MGUS. Additional gene expression measurements are ongoing in a larger cohort of IgM-MGUS patients. Table 1. Upregulated gene sets in monoclonal vs. polyclonal IgM-MGUS GENE SET NAME REACTOME_XENOBIOTICS REGULATION_OF_CHROMOSOME_ORGANIZATION_AND_BIOGENESIS Downregulated gene sets in monoclonal vs. polyclonal IgM-MGUS Table 2. Linear regression results of both IgM and MC on UBTF expression GENE SET NAME REACTOME_ROLE_OF_DCC_IN_REGULATING_APOPTOSIS REACTOME_P38MAPK_EVENTS REACTOME_EARLY_PHASE_OF_HIV_LIFE_CYCLE REACTOME_MRNA_DECAY_BY_3_TO_5_EXORIBONUCLEASE KEGG_NICOTINATE_AND_NICOTINAMIDE_METABOLISM CHROMATIN_ASSEMBLY_OR_DISASSEMBLY ESTABLISHMENT_AND_OR_MAINTENANCE_OF_CHROMATIN_ARCHITECTURE PROTEIN_DNA_COMPLEX_ASSEMBLY RESPONSE_TO_DNA_DAMAGE_STIMULUS CHROMATIN_ASSEMBLY CHROMOSOME_ORGANIZATION_AND_BIOGENESIS DOUBLE_STRAND_BREAK_REPAIR CHROMATIN_REMODELING CENTROSOME_ORGANIZATION_AND_BIOGENESIS MICROTUBULE_ORGANIZING_CENTER_ORGANIZATION_AND_BIOGENESIS Table 3 Coefficient p-value Intercept 7.0738801 6.47e-12 IgM -0.0021593 3.78e-07 MC 1.1925055 0.000501 IgM:MC 0.0010577 0.000152 Disclosures No relevant conflicts of interest to declare.

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Leal, Paula Azevedo Borges, Adrilena Lopes Adriano, Marcelle Parente Breckenfeld, Igor Santos Costa, Antônio Renê Diógenes de Sousa, and Heitor de Sá Gonçalves. "Rosai-Dorfman disease presenting with extensive cutaneous manifestation - Case report." Anais Brasileiros de Dermatologia 88, no. 2 (2013): 256–59. http://dx.doi.org/10.1590/s0365-05962013000200014.

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Rosai-Dorfman disease is a benign, self-limited, idiopathic proliferative histiocytic disorder. It was first described in 1969 by Rosai and Dorfman. In its typical form the disease is characterized by extensive cervical lymphadenopathy associated with fever, polyclonal gammopathy and leukocytosis with neutrophilia. The skin is the most common site affected. Extranodal manifestations have been reported in 43% of cases. In this study, we report an atypical case of Rosai-Dorfman disease in a female with massive cutaneous manifestation on the thigh, associated with a minimal lymphadenopathy limited to the regional inguinal lymph nodes.

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Zamarin, Dmitriy, Sean Devlin, Maria Arcila, et al. "Reactive Polyclonal Gammopathy Associated with Polyclonal Plasmacytosis Is Common in Patients with Multiple Myeloma Receiving Prolonged Lenalidomide Therapy: A Retrospective Study of 104 Patients." Blood 120, no. 21 (2012): 4033. http://dx.doi.org/10.1182/blood.v120.21.4033.4033.

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Abstract Abstract 4033 BACKGROUND: Prolonged lenalidomide treatment is frequently used in patients with multiple myeloma (MM), both in the upfront and relapsed settings. We have previously reported a small series of 6 patients receiving prolonged lenalidomide treatment who presented with a polyclonal IgA gammopathy characterized by a marked elevation in the serum IgA level, polyclonal plasmacytosis in the bone marrow, and without any evidence of clinical disease progression. Although the immunologic mechanism underlying this observation is currently under investigation, it is important to recognize and characterize its incidence, clinical features, and prognostic significance. For these purposes, we have undertaken a retrospective analysis of all patients treated at MSKCC with prolonged course of lenalidomide. METHODS AND RESULTS: We retrospectively identified 104 patients with MM who received a prolonged course of lenalidomide (>6 months). Among these patients, 21 (20%) were noted to have polyclonal immunoglobulin (Ig) elevation above the upper limit of normal during lenalidomide therapy, affecting IgA in 13, IgG in 6, and both IgA and IgG in 2 patients. All 21 patients were without evidence of relapse or progression (R/POD) by serologic or clinical criteria at the time of polyclonal Ig elevation. In 15 patients the polyclonal Ig did not involve the initial monoclonal isotype. The median time from lenalidomide initiation to polyclonal elevation of Ig level was 10.9 months (range 2 to 38.6 months), with the median peak IgA level of 587 mg/dl (range 374 to 1190 mg/dl), and the median peak IgG level of 1800 mg/dl (range 1575 to 2650 mg/dl). Bone marrow aspirates and biopsies were available in 12 patients during the period of Ig elevation and the median plasmacytosis was 12% (range 5 to 20%) on the aspirate. Immunohistochemical (IHC) studies of the bone marrow biopsy showed moderate increase in CD138+ cells without light chain restriction. IHC using IgA and IgG antibody staining in the patients with IgA elevation confirmed that most plasma cells were IgA-producing and were not consistent with the original myeloma clone. To evaluate for the association of polyclonal gammopathy with progression free survival, we performed a landmark analysis on all 104 patients based on the magnitude of the absolute Ig elevation measured at 6 months after initiation of lenalidomide. The patients were divided into 2 groups on the basis of the median absolute elevation in the levels of IgA (40 mg/dl) or IgG (150 mg/dl) from the baseline prior to therapy initiation to 6 months after starting the treatment. Statistical comparison was limited by the small number of patients who had R/POD in the sample (n=16), but there was a trend toward improved PFS in the patients who achieved absolute IgA elevation >40mg/dl, though any difference was attenuated by 36 months following the 6-month landmark (logrank p-value: 0.54). Interestingly, when focusing exclusively on the 16 patients with R/POD during the followup, the median time to progression was 27.5 months and 13.1 months in patients with absolute IgA elevation >40mg/dl (n=10), and those with absolute IgA elevation <40mg/dl (n=6) at the 6 month landmark, respectively. CONCLUSIONS: Polyclonal gammopathy with Ig levels exceeding the normal range associated with polyclonal plasmacytosis occurs with a relatively high frequency (20%) in patients treated with prolonged courses of lenalidomide. Awareness of this effect is important especially in view of the associated significant bone marrow plasmacytosis, which may mistakenly be construed as R/POD in patients who are actually responding to treatment. In addition, the absolute elevation in the IgA level measured at 6 months post initiation of treatment may be a prognostic indicator of progression, with high elevations potentially indicating an extended benefit from lenalidomide treatment. Further studies are needed to validate these observations and to elucidate their mechanism. Disclosures: Giralt: Celgene: Honoraria, Research Funding. Landau:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding. Hassoun:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding.

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TAHER M.H. EL ZANATY, M.D., MOHAMED A. R. MOSTAFA, M. Sc ;., and AYMEN M. R. FODA, M. D. ;. NEHAD M. TAWFIK, M.D. "Hepatitis C Positive Patients in Relation to Polyclonal and Monoclonal Gammopathy: An Egyptian Experience." Medical Journal of Cairo University 90, no. 6 (2022): 1225–30. http://dx.doi.org/10.21608/mjcu.2022.257441.

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Geigy, Caroline, Barbara Riond, Carla Rohrer Bley, Paula Grest, Patrick Kircher, and Hans Lutz. "Multiple myeloma in a dog with multiple concurrent infectious diseases and persistent polyclonal gammopathy." Veterinary Clinical Pathology 42, no. 1 (2012): 47–54. http://dx.doi.org/10.1111/vcp.12018.

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Sobue, G., T. Yanagi, and Y. Hashizume. "Chronic progressive sensory ataxic neuropathy with polyclonal gammopathy and disseminated focal perivascular cellular infiltrations." Neurology 38, no. 3 (1988): 463. http://dx.doi.org/10.1212/wnl.38.3.463.

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Bhargavi, Reddy Metta* Krishna Samalla. "Statistical Study and Analysis of Plasma Proteins." International Journal of Pharmaceutical Sciences 3, no. 4 (2025): 1925–33. https://doi.org/10.5281/zenodo.15224035.

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Serum albumins are important in regulating blood volume by maintaining the oncotic pressure (also known as colloid osmotic pressure) of the blood compartment, bovine serum albumin (cattle serum albumin) or BSA, often used in medical and molecular biology labs. Serum albumin is the main protein of human blood plasma. It binds water, cations (such as Ca2+, Na+ and K+), fatty acids, hormones, bilirubin, thyroxin (T4) and pharmaceuticals (including barbiturates), its main function is to regulate the Oncotic pressure of blood. Alpha and beta globulins function as enzymes and proteins that transport compounds in the body. Gamma globulins act as the antibody defense against antigen invasion[1-2] Gamma globulins are manufactured in cells of the immune system known as lymphocytes and plasma cell, Blood plasma, which is usually about 4% of the body weight, consists of many constituents including H2O, nutrients and metabolites, proteins, various hormones and electrolytes.[1] The normal total plasma protein concentration ranges from 5.5-8.9 gm/dl in domestic animal species, and it is a complex mixture including simple proteins, glyco proteins and various lipo protein hous ands of antibodies (immunoglobulins) are also present in plasma, although under normal conditions the amount of any one is usually quite low.

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Bnatig, Fahad, Leen Raddaoui, Talal Hijji, and Lina El Kibbi. "Mixed Cryoglobulinemia in a Patient with Juvenile Idiopathic Arthritis." Case Reports in Rheumatology 2019 (June 6, 2019): 1–2. http://dx.doi.org/10.1155/2019/5858106.

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Cryoglobulinemia is a rare illness of cryoglobulin accumulation in the blood which can typically present with arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy. It is classified as mixed cryoglobulinemia when cryoglobulins contain more than one immune component such as IgM rheumatoid factor and polyclonal IgG. Typically, it presents in the setting of clonal hematologic disease, viral infection, or certain connective tissue diseases. Herein, we report the case of a 24-year-old man diagnosed and treated as mixed cryoglobulinemia in the setting of juvenile idiopathic arthritis (JIA). Investigations for viral etiologies, including HBV, HCV, and HIV, and all serologic tests were negative. Additionally serum protein and urine protein electrophoresis did not reveal monoclonal gammopathy; however, testing for plasma cryoglobulins was positive, and qualitative analysis revealed a faint polyclonal pattern. Thus, he was diagnosed with cryoglobulinemia in the setting of JIA, which has not been reported in the literature before. He dramatically improved upon initiation of rituximab and methotrexate.

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Jacobs, Joannes F. M., Renate G. van der Molen, and David F. Keren. "Relatively Restricted Migration of Polyclonal IgG4 May Mimic a Monoclonal Gammopathy in IgG4-Related Disease." American Journal of Clinical Pathology 142, no. 1 (2014): 76–81. http://dx.doi.org/10.1309/ajcp41xcvbheqcel.

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Dhodapkar, Madhav V. "MGUS to myeloma: a mysterious gammopathy of underexplored significance." Blood 128, no. 23 (2016): 2599–606. http://dx.doi.org/10.1182/blood-2016-09-692954.

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Abstract All cases of multiple myeloma (MM) are preceded by precursor states termed monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion, wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also established early during the MGUS phase. Although the genetic features of MGUS or SMM cells at baseline may predict disease risk, transition to MM involves altered growth of preexisting clones. Recent advances in mouse modeling of MGUS suggest that the clinical dormancy of the clone may be regulated in part by growth controls extrinsic to the tumor cells. Interactions of MGUS cells with immune cells, bone cells, and others in the bone marrow niche may be key regulators of malignant transformation. These interactions involve a bidirectional crosstalk leading to both growth-supporting and inhibitory signals. Because MGUS is already a genetically complex lesion, application of new tools for earlier detection should allow delineation of earlier stages, which we term as pre-MGUS. Analyses of populations at increased risk of MGUS also suggest the possible existence of a polyclonal phase preceding the development of MGUS. Monoclonal gammopathy in several patients may have potential clinical significance in spite of low risk of malignancy. Understanding the entire spectrum of these disorders may have broader implications beyond prevention of clinical malignancy.

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Kim, J. W., J. H. Park, J. W. Park, H. J. Doh, G. S. Heo, and K. J. Lee. "Quantitative analysis of serum proteins separated by capillary electrophoresis." Clinical Chemistry 39, no. 4 (1993): 689–92. http://dx.doi.org/10.1093/clinchem/39.4.689.

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Abstract The possibility of open tubular capillary electrophoresis for clinical diagnostic use is examined. Capillary electrophoresis was performed in an untreated 50 microns (i.d.) x 100 cm (65 cm to detector) capillary with detection of absorbance at 200 nm. Conditions for the separation of serum proteins without adsorption to the capillary surface were established. Quantitative analyses of serum samples from 38 patients with liver cirrhosis, nephrotic syndrome, or polyclonal gammopathy by capillary electrophoresis were done and the results were compared with those by conventional agarose gel electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All samples were analyzed in duplicate. We evaluated linearity of response, within-run CV, and the correlation between capillary electrophoresis and agarose gel electrophoresis.

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Laskar, DB, K. Shafique, C. Lu, and A. Zuretti. "MP8: MONOCLONAL GAMMOPATHY CHARACTERIZATION USING SERUM PROTEIN ELECTROPHORESIS IN A MAJOR URBAN POPULATION." Journal of Investigative Medicine 64, no. 3 (2016): 807.2–808. http://dx.doi.org/10.1136/jim-2016-000080.20.

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Purpose of StudySerum protein electrophoresis (SPEP) with subsequent immunofixation (IF) are clinical laboratory techniques used to evaluate a wide-range of disorders where abnormal serum protein quantities are characteristic (e.g. multiple myeloma (MM), MGUS, amyloidosis, HIV/AIDS, SLE, CLL/NHL). Thus, it is important to identify or exclude malignancy when considering the analyses. Our aim is to characterize SPEP patients from our institution, a predominantly black population.Methods UsedWe retrospectively reviewed 50 patient's SPEP/IF results. Data recorded were SPEP/IF results, monoclonal immunoglobulin (Ig) identity, clinical diagnoses, age, race and gender. Univariate analysis was used to describe patient demographics. Parametric analysis was used to compare the monoclonal gammopathy (MG) group versus non-MG group.Summary of ResultsAge range was 12–86 years, mean age was 62 years and male to female ratio was 1:3.5. Forty-eight (96%) patients identify as black, 1 (2%) Asian and 1 (2%) white. SPEP patterns showed 1 (2%) patient had acute inflammation, 3 (6%) had chronic inflammation, 24 (48%) were inconclusive, 16 (32%) had MGs, 3 (6%) had normal results and 3 (6%) had polyclonal bands (table 1). Among MG patients, IgG was most common isotype (75%), kappa was most common light chain (58%) and IgG kappa was most common (44%). Mean age was 69 years for MG patients and 58 years for non-MG patients.MM was identified in 9 (18%) patients; 89% (8/9) had normal total protein (TP) levels and 1 (11%) had increased TP. Neuropathy was seen in 7 (14%) patients; 71% (5/7) had polyclonal gamma Ig increase, and 1 (14%) case with co-HIV infection had monoclonal IgG kappa. Seven (14%) patients had CKD, 4 (8%) had HIV/AIDS, 3 (6%) had anemia, 3 (6%) had MGUS, 1 (2%) had SLE and the remaining 16 (32%) had other co-morbidities (i.e. HTN, DM, CAD, etc.).ConclusionsSPEP/IF analyses were used to characterize 50 patients. A wide-range of disorders were observed. MG patients were 11 years older than non-MG patients. IgG kappa was most common MG. Our study showed female-predominance. This study shows SPEP utility to discern various disorders observed at our institution.Abstract MP8 Figure 1

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Chauvet, Sophie, Lubka Roumenina, Maria Chiara Marinozzi, et al. "Role of monoclonal and polyclonal immunoglobulins in AP dysregulation in C3 glomerulopathy associated with monoclonal gammopathy." Molecular Immunology 89 (September 2017): 174. http://dx.doi.org/10.1016/j.molimm.2017.06.155.

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Cunha, B. A., J. E. Hage, and Y. Nouri. "Fever of unknown origin (FUO) in an immunocompetent adult due to cytomegalovirus (CMV) with polyclonal gammopathy." Infection 40, no. 3 (2011): 327–30. http://dx.doi.org/10.1007/s15010-011-0191-8.

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Chandrasekaran, Visalam, and Mark T. Friedman. "Symptomatic hyperviscosity syndrome with polyclonal gammopathy responding to therapeutic plasmapheresis in a patient with myelodysplastic syndrome." Journal of Clinical Apheresis 11, no. 1 (1996): 48–49. http://dx.doi.org/10.1002/(sici)1098-1101(1996)11:1<48::aid-jca10>3.0.co;2-t.

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Lee, Nuri, Seri Jeong, Kibum Jeon, Wonkeun Song, and Min-Jeong Park. "Development and validation of a deep learning-based protein electrophoresis classification algorithm." PLOS ONE 17, no. 8 (2022): e0273284. http://dx.doi.org/10.1371/journal.pone.0273284.

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Background Protein electrophoresis (PEP) is an important tool in supporting the analytical characterization of protein status in diseases related to monoclonal components, inflammation, and antibody deficiency. Here, we developed a deep learning-based PEP classification algorithm to supplement the labor-intensive PEP interpretation and enhance inter-observer reliability. Methods A total of 2,578 gel images and densitogram PEP images from January 2018 to July 2019 were split into training (80%), validation (10%), and test (10.0%) sets. The PEP images were assessed based on six major findings (acute-phase protein, monoclonal gammopathy, polyclonal gammopathy, hypoproteinemia, nephrotic syndrome, and normal). The images underwent processing, including color-to-grayscale and histogram equalization, and were input into neural networks. Results Using densitogram PEP images, the area under the receiver operating characteristic curve (AUROC) for each diagnosis ranged from 0.873 to 0.989, and the accuracy for classifying all the findings ranged from 85.2% to 96.9%. For gel images, the AUROC ranged from 0.763 to 0.965, and the accuracy ranged from 82.0% to 94.5%. Conclusions The deep learning algorithm demonstrated good performance in classifying PEP images. It is expected to be useful as an auxiliary tool for screening the results and helpful in environments where specialists are scarce.

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Amo, Yasuyuki, Fuyuki Ogata, Seigo Okabe, Kohzoh Yonemoto, and Kensei Katsuoka. "CD56‐Positive Cutaneous Lymphoma with Multicentric Castleman's Disease‐like Systemic Manifestations." Journal of Dermatology 28, no. 12 (2001): 746–52. http://dx.doi.org/10.1111/j.1346-8138.2001.tb00071.x.

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AbstractWe report a 55‐year‐old Japanese male with CD56+ cutaneous lymphoma. The patient had multiple cervical lymphadenopathy, a red nodule on his neck, and parotid gland nodularity. Histologic features of the biopsied cervical lymph node showed follicular hyperplasia with numerous plasma cells. A biopsied skin specimen of the nodule on his neck demonstrated dense infiltration of atypical large lymphocytes into the dermis. Immunohistochemical study of this specimen revealed CD3+, CD4+, and CD56+ expression in the majority of neoplastic cells. Polymerase chain reaction assays for the detection of Epstein‐Barr virus sequences were positive for lymph node and skin DNA. Laboratory examinations showed polyclonal gammopathy, pancytopenia, and high serum interleukin‐6 levels. These clinical and histological findings resembled those of multicentric Castleman's disease.

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Mori, Masataka, Kenichiro Kinoshita, Nobutaro Ban, Yasuaki Yamada, and Hiroshi Shiku. "Activated t-lymphocytes with polyclonal gammopathy in patients with human t-lymphotropic virus type i?associated myelopathy." Annals of Neurology 24, no. 2 (1988): 280–82. http://dx.doi.org/10.1002/ana.410240220.

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Kim, Yu Ri, Soo Jeong Kim, Yundeok Kim, et al. "Prognostic Role Of Monoclonal and Polyclonal Gammopathy Measured By Serum Free Light Chain and Immunofixation In Diffuse Large B-Cell Lymphoma." Blood 122, no. 21 (2013): 5112. http://dx.doi.org/10.1182/blood.v122.21.5112.5112.

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Abstract Background Serum free light chain (FLC) assay has been used to evaluate the prognosis of several hematologic malignancies. We evaluated the prognostic role of monoclonal gammopathy (MG) and polyclonal gammopathy (PG) measured by serum FLC and immunofixation (IF) in DLBCL. Patients and methods We retrospectively reviewed 115 patients with DLBCL who treated with rituximab containing chemotherapy. MG was defined as elevated kappa (κ) or lambda (λ) FLC with abnormal κ to λ ratio or positive IF and PG was defined as elevated κ and/or λ FLC with normal κ to λ ratio and negative IF. Results Fifty-six (48.7%) patients had an elevated FLC. Twenty (17.4%) patients had MG and 39 (33.9%) patients accompanied by a PG. Two-year overall survival (OS) was 89.2%, and 2-year event-free survival (EFS) was 88.4%. Elevated FLC was associated with inferior OS and EFS (p=0.013, p=0.012). Patients with MG had an inferior OS and EFS compared to patients with normal FLC (p=0.006, p=0.011). In multivariate analysis, both elevated FLC and MG showed the significance for OS (HR 4.57, 95% CI 1.43-14.60, p=0.001 and HR 5.63, 95% CI 1.50-21.09, p=0.010). Elevated FLC did not show the significantly shorter OS or EFS in non-germinal center B-cell (GCB) type according to the Han’s criteria. However, MG was a significant prognostic factor for OS and EFS in non-GCB type (HR 6.28, 95% CI 1.21-32.62, p=0.029, HR 6.38, 95% CI 1.58-25.74, p=0.009). Conclusion It important to evaluate the associated MG and PG using serum FLC and IF for predicting the prognosis of DLBCL, especially in non-GCB subtype. Disclosures: No relevant conflicts of interest to declare.

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Biederman, Laura, Anjali A. Satoskar, Mohankumar Doraiswamy, et al. "Can Antinuclear Antibodies (ANA) be Monoclonal?" Case Reports in Nephrology 2021 (September 30, 2021): 1–6. http://dx.doi.org/10.1155/2021/7006466.

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Background. Nuclear staining by immunofluorescence in a kidney biopsy is often seen in patients with positive antinuclear antibodies (ANA) in the serum. These ANA are usually polyclonal, but herein we report 9 cases with an unusual finding of monoclonal nuclear staining by immunofluorescence on kidney biopsy. Case Presentation. Nine cases with predominant stain for kappa or lambda light chain were identified by searching the renal pathology laboratory database for the past 10 years. All cases had positive stain for only kappa (six cases) or lambda (three cases) light chain in the nuclei. Eight out of nine cases had positive nuclear IgG stain, and one case had positive nuclear IgA stain. Among cases with positive nuclear IgG staining, six cases were positive for IgG1 subclass, one case was positive for IgG2 subclass, and one case was positive for IgG3 subclass. All patients with positive IgG nuclear stain, who had testing for ANA, had positive ANA. Patients with positive IgG1 subclass did not have monoclonal protein in the serum or urine, but the patient with positive IgG2 subclass and lambda light chain stain in the nuclei had IgG lambda monoclonal gammopathy. Conclusions. We identified a new unique pattern of nuclear stain by immunofluorescence in kidney biopsies that suggests the presence of monoclonal ANA. Workup for underlying monoclonal gammopathy is warranted in such patients.

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Anandram, Seetharam, Lakhvir Kaur Assi, Tracy Lovatt, et al. "Elevated, combined serum free light chain levels and increased mortality: a 5-year follow-up, UK study." Journal of Clinical Pathology 65, no. 11 (2012): 1036–42. http://dx.doi.org/10.1136/jclinpath-2012-200910.

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AimsAbnormal serum free light chain (FLC) ratios are diagnostically important in almost all plasma cell disorders. However, absolute increases in polyclonal FLC levels are often discarded as inconsequential. Here we report an association between increased combined polyclonal FLC (cFLC: FLCκ plus FLCλ) concentrations and mortality.Methods723 patients sent for 30 routine haematological assessments were enrolled. Patients with a confirmed monoclonal gammopathy were removed. The remaining 527 patients were followed up for up to 4.5 years. Statistical analysis was performed using SPSS (V.19).ResultsDuring follow-up, there were 99 deaths (18.8%). Kaplan-Meier survival analysis revealed 29% of these deaths occurred within the first 100 days (N=29). Multivariate analysis identified only cFLC >65 mg/l, albumin <33 g/l and estimated glomerular filtration rate <30 ml/min/1.73 m2 to be independently associated with mortality within 100 days and 4.5 years with, cFLC having the highest HR of 7.1. A simple risk stratification model based only on albumin and cFLC identified 86% mortality within 100 days and 62% over 4.5 years.ConclusionsElevated cFLC is significantly associated with increased mortality and with albumin can be used to identify patients at risk of mortality at 4.5 years with high-risk patients detected within 100 days.

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Okano, M., S. Matsumoto, T. Osato, Y. Sakiyama, G. M. Thiele, and D. T. Purtilo. "Severe chronic active Epstein-Barr virus infection syndrome." Clinical Microbiology Reviews 4, no. 1 (1991): 129–35. http://dx.doi.org/10.1128/cmr.4.1.129.

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Reports of unusually severe lymphoproliferative disorders associated with extremely high antibody titers against Epstein-Barr virus (EBV) have recently increased. The syndrome, which we designated severe chronic active EBV infection syndrome, is characterized by persistent or intermittent fever, lymphadenopathy, and hepatosplenomegaly and primarily affects children and young adults. Polyclonal gammopathy and bone marrow suppression are generally observed, and some patients develop B-cell or T-cell lymphoproliferation or lymphoma. Frequently, EBV genomes are detectable in tissues infiltrated with lymphoid cells. Additionally, it is difficult to establish spontaneous or B95-8 EBV-induced cell lines despite the expression of an activated EBV infection. We review and report here the published medical literature and our own experience regarding patients with severe chronic active EBV infection syndrome in an attempt to understand this enigmatic syndrome and the possible pathogenetic mechanism(s) responsible for this disorder.

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Hughes, Derralynn A., Veronique M. Duke, Robert J. Baker, Faith Wright, Letizia Foroni, and Mehta B. Atul. "High Prevalence of B-Cell Clonality in Patients with Gaucher’s Disease." Blood 104, no. 11 (2004): 2391. http://dx.doi.org/10.1182/blood.v104.11.2391.2391.

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Abstract Haematological malignancy occurs in patients with Gaucher Disease at an incidence 15 fold greater than in the non-Gaucher population. Little is understood regarding the role of glucosyl ceramide acculmulation in immune system pathology or in the development of cancer in Gaucher Disease. Furthermore whilst enzyme replacement therapy (ERT) with recombinant glucocerebrosidase has been successful in reversing symptoms relating to bulk storage e.g. hepatosplenomegaly and bone marrow infiltration, its effects on the pathogenesis of malignancy are unknown. We have measured the levels of immunlglobulin in 63 patients with Gaucher disease receiving ERT for up to 10 years and have investigated the incidence of clonal B cell populations by flow cytometry, immunoglobulin heavy chain gene rearrangement analysis, and measurement of paraproteins by electropheresis and immunofixation. Evidence of high level of immune stimulation was found by morphological and immunoglobin analysis. Examination of peripheral blood revealed atypical lymphocyte morphology in 53% Gaucher patients whilst 50.7% patients were found to have levels of immunoglobulins significantly higher than those found in healthy adults. There were no sex or age related differences between those patients with elevated immunoglobulins (18 male; median age 40yrs, 14 female; median age 48 years) and those with normal levels (13 male median age 41 years, 18 female; median age 47.5 years). Elevation of one, two or three immunoglobulin subclasses was detected in 36%, 13.1% and 1.6% of patients respectively. In patients with IgM polyclonal gammopathy levels of immunoglobulin normalised with ERT. This was not the case with IgG and IgA gammopathies which were unaffected by ERT even after 10 years of treatment. No patient with normal immunoglobulin levels prior to treatment developed a gammopathy after initiation of ERT Evidence of B-cell clonality was found in 23% of patients. 13.4% had measurable paraproteins, 9.3% exhibited a IgM+, IgD+, FMC7+ monoclonal population by flow cytometry and 26.9% had clonal immunoglobulin heavy chain gene rearrangements of which 43% were in frame and therefore functional. There was no relationship between genotype, absolute lymphocyte count (median 1.5 x109 in all groups) and age (median 45.5 years with clonal population and 44 years without) or duration of ERT (median 5.25 years with clonal population and 6.5 years without) and the existence of clonality. Our data confirms the existence of high levels of immune stimulation and B cell clonality in patients with Gaucher disease. In contrast to features of bulk storage of glucosyl ceramide, the polyclonal gammopathy and B cell clonality is not reversed by ERT and may therefore occur at low levels of storage. The existence of multiple markers of clonality will allow the response of individual patients to different modalities of therapy to be followed, and the pathophysiology of haematological malignancy to be further assessed.

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Piehler, Armin P., Nina Gulbrandsen, Peter Kierulf, and Petter Urdal. "Quantitation of Serum Free Light Chains in Combination with Protein Electrophoresis and Clinical Information for Diagnosing Multiple Myeloma in a General Hospital Population." Clinical Chemistry 54, no. 11 (2008): 1823–30. http://dx.doi.org/10.1373/clinchem.2008.106153.

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Abstract Background: Serum free light chain (SFLC) measurements have recently come into use as an aid for diagnosing monoclonal gammopathy. We evaluated SFLC measurements in combination with serum protein electrophoresis (SPE) and clinical information for diagnosing multiple myeloma (MM) in a hospital population. Methods: We measured SFLCs in 3818 sera received for SPE over a 1-year period when patient symptoms or biochemical findings suggested myeloma-related tissue damage (n = 1067). We reviewed SPE and SFLC results from 489 patients together with their final diagnoses obtained from the hospital information technology department. Results: SFLC measurement, combined with SPE and clinical information, allowed identification of 95% of patients (38 of 40) with previously undiagnosed MM, macroglobulinemia, or primary amyloidosis. Additionally, we identified 45 patients with monoclonal gammopathy of undetermined significance (MGUS) and 4 with plasmacytoma. Of patients followed at our hospital in whom SFLCs were not measured, only 1 patient was diagnosed with MM. This patient had anemia and was mistakenly not tested for SFLCs. An abnormal κ/λ ratio was found in 26 of 29 patients with MM but also in 36 of 203 patients with renal impairment, polyclonal immunoresponse, or other nonhematological diagnoses. None of the 203 patients with nonhematological disease had a κ/λ ratio &lt;0.05 or &gt;10. Conclusions: The combined use of SPE, SFLC measurements, and clinical criteria allows MM to be efficiently diagnosed or excluded based on serum measurements only.

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Uddin, Mohammed Mosleh, Md Mizanur Rahman, Syeda Adib Sultana, and Debashish Saha. "Superiority of Serum Immunofixation Electrophoresis over Serum Protein Electrophoresis in the Diagnosis of Multiple Myeloma." Journal of Bangladesh College of Physicians and Surgeons 36, no. 3 (2018): 95–100. http://dx.doi.org/10.3329/jbcps.v36i3.37031.

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Background: Multiple Myeloma (MM) is a neoplasm of B cell lineage characterized by excessive proliferation of abnormal plasma cells, secreting abnormal immunoglobulin causing monoclonal gammopathy which can be detected by the presence of M protein in serum and urine electrophoresis.Aim: Present study is aimed to detect and quantify monoclonal gamma globulins by SPEP and IFE in suspected case of MM and other plasma cell dyscrasias and also to find out the discrepant findings between SPEP and IFE.Methods: A retrospective observational study was carried out on clinically highly suspected cases of Multiple Myeloma (MM) presenting with backache, asthenia and generalized weakness at Armed forces Institute of Pathology(AFIP), Dhaka cantonment from January 2015 to July 2016. A total of 140 blood samples were collected and subjected to serum protein electrophoresis (SPEP) and Immunofixation electrophoresis (IFE). IFE identifies the type of heavy (IgG, IgM or IgA) and light chain (either kappa or lambda in suspected cases of MMResults: Out of 140 cases, SPEP identified monoclonal band in 62 cases and either non-specific findings or polyclonal band in 78 cases. At the same time immunofixation electrophoresis (IFE) which was done on all samples detected another 14 cases of M-band in addition to earlier 62 cases of monoclonal gammopathy by SPEP. Among 140 cases, SPEP detected M-band in 62 cases, whereas IFE identified monoclonal band in 76 cases. So in the remaining 14 cases (10%) small sharp spikes of monoclonal band was found only by IFE whereas SPEP failed to detect those 14 cases.Conclusion: SPEP is an easy to perform laboratory test which can be used for detection and quantification of monoclonal gammopathy but there is some limitation in detecting monoclonal band by SPEP. IFE is more sensitive to detect the monoclonal band than SPEP. So both SPEP and IFE should be done simultaneously for precise diagnosis of MM and related disorders.J Bangladesh Coll Phys Surg 2018; 36(3): 95-100

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Nguyen, Yann, Jérôme Stirnemann, Florent Lautredoux, et al. "Immunoglobulin Abnormalities in Gaucher Disease: an Analysis of 278 Patients Included in the French Gaucher Disease Registry." International Journal of Molecular Sciences 21, no. 4 (2020): 1247. http://dx.doi.org/10.3390/ijms21041247.

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Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40–9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

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Kubagawa, H., L. F. Bertoli, J. C. Barton, W. J. Koopman, J. Mestecky, and M. D. Cooper. "Analysis of paraprotein transport into the saliva by using anti-idiotype antibodies." Journal of Immunology 138, no. 2 (1987): 435–39. http://dx.doi.org/10.4049/jimmunol.138.2.435.

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Abstract To determine the extent of clonal involvement of the secretory immune system and the origin of salivary immunoglobulins (Ig) in monoclonal gammopathy patients, saliva and serum samples were collected from five affected individuals (two IgA myelomas, one IgG myeloma, one IgG benign monoclonal gammopathy, and one IgM lymphoma) and were assayed for the presence of monoclonal Ig. Purified polyclonal or monoclonal anti-idiotype (Id) antibodies were prepared against each of the isolated serum paraproteins. In all five individuals, the patient saliva samples inhibited the binding of 125I-labeled homologous Ig to the corresponding anti-Id antibodies, but normal saliva did not. The concentration of Id in patients' saliva varied from 1 to 400 micrograms/ml; i.e., 0.004 to 1.0% of the corresponding serum values. Saliva of a lymphoma patient whose IgM kappa protein exhibited rheumatoid factor (RF) activity also contained RF. The salivary Id-bearing molecules were found to have the same Ig isotype as the serum paraproteins. The myeloma IgA represented a minor component (0.4 and 3.9%) of the total salivary IgA. The salivary IgA myeloma proteins were associated at least in part with secretory component, but the salivary IgG paraproteins were not. In an IgA myeloma patient, a minority (17%) of the IgA+ plasma cells found in the lacrymal gland biopsy specimen were Id+, whereas the great majority (98%) of bone marrow IgA plasma cells were Id+. The results suggest active transport rather than passive transudation of myeloma IgA into the patients' saliva, and the integrity of the secretory immune system was not compromised by the neoplastic process.

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Mathis, Jason, Matthew Zirwas, Camille T. Elkins, Mark Bechtel, and Benjamin H. Kaffenberger. "Persistent and progressive purpura in a patient with an elevated rheumatoid factor and polyclonal gammopathy (hypergammaglobulinemic purpura of Waldenström)." Journal of the American Academy of Dermatology 72, no. 2 (2015): 374–76. http://dx.doi.org/10.1016/j.jaad.2013.02.020.

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