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Journal articles on the topic 'Light chain restriction'

Author: Grafiati

Published: 7 June 2025

Last updated: 16 July 2025

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1

Flotte, T. J., and L. G. Baird. "Immunoglobulin light and heavy chain isotypes in skin diseases: restricted distribution in bullous pemphigoid and linear IgA bullous dermatosis." Journal of Immunology 136, no. 2 (1986): 491–96. http://dx.doi.org/10.4049/jimmunol.136.2.491.

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Abstract To assess the heterogeneity of immunoglobulins involved in various skin diseases, direct and indirect immunofluorescence studies of skin biopsies and sera, respectively, for kappa and lambda light chains, were performed. The anti-basement membrane zone (anti-BMZ) antibodies of patients with bullous pemphigoid showed a predominance of kappa light chains, and patients with linear IgA bullous dermatosis showed a predominance of one light chain that was sometimes kappa and sometimes lambda. The bullous pemphigoid autoantibodies were then studied for IgG subclass distribution; a predominance of IgG4 was found. Although other explanations are possible, the light chain restriction in bullous pemphigoid most likely reflects heavy chain restriction and preferential association of heavy and light chain isotypes. The basis of the heavy chain restriction is not apparent. The light chain restriction in linear IgA bullous dermatosis may represent a restricted idiotypic repertoire.

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2

Ribeiro, Catarina Isabel, Ana Marta Gomes, Rute Carmo, and Ana Luís. "Membranous nephropathy with light chain restriction." Journal of Nephropathology 10, no. 1 (2020): e03-e03. http://dx.doi.org/10.34172/jnp.2021.03.

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3

Lopez De Pablo, Javier Carbayo. "Membranous Glomerulopathy with Light Chain Restriction." Nephrology & Renal Therapy 7, no. 3 (2021): 1–4. http://dx.doi.org/10.24966/nrt-7313/100067.

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Membranous nephropathy is considered the main cause of idiopathic nephrotic syndrome in adults. Mostly caused from the deposition of polytypic immune complexes along the subepitelial slope of the glomerular basement membrane

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4

D'Ardia, Angela, Valeria Ciliberti, Pio Zeppa, and Alessandro Caputo. "Observations on hematogones with light chain restriction." Leukemia Research Reports 17 (2022): 100316. http://dx.doi.org/10.1016/j.lrr.2022.100316.

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5

Kapur, Umesh, Kevin Barton, Raoul Fresco, David J. Leehy, and Maria M. Picken. "Expanding the Pathologic Spectrum of Immunoglobulin Light Chain Proximal Tubulopathy." Archives of Pathology & Laboratory Medicine 131, no. 9 (2007): 1368–72. http://dx.doi.org/10.5858/2007-131-1368-etpsoi.

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Abstract Context.—In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. Objective.—To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. Design.—We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. Results.—By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post–kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. Conclusions.—Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both κ and λ light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

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6

Priyadarshini, Sarah, Debdatta Basu, Rakhee Kar, and T. Dutta. "Comparison Of Histomorphology, Angiogenesis and Proliferation in Kappa and Lambda Restricted Plasma Cell Myelomas with Its Effect on Prognosis." Journal of Complementary Medicine Research 14, no. 3 (2023): 77. http://dx.doi.org/10.5455/jcmr.2023.14.03.13.

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Aims Of the Study: To study the type of light chain restriction and correlate it with the morphological parameters, proliferation index, angiogenesis and clinical parameters. Materials And Methods: The study includes 46 cases of myeloma diagnosed over the period of five years. The histomorphological features like plasma cell morphology, percentage of plasma cells and pattern of infiltration were studied. Immunohistochemistry for kappa and lambda light chains was done. Angiogenesis was assessed by calculating the microvessel density (MVD) using anti CD34 immunohistochemistry. Proliferation was assessed immunohistochemically using Ki67 by comparing with anti CD38 which was used to highlight the plasma cells. Results: The cases with kappa light chain restriction had significantly less of poorly differentiated morphology (7.4% vs 36.8%; p=0.02) and diffuse pattern of infiltration (22% vs 63%; p=0.01) compared to lambda. The kappa group also had lower MVD (9.9 vs 16.5; p=0.02) and proliferation index (4.7 vs 94; p=0.04) compared to the lambda. Conclusion: Therefore, the type of light chain restriction is also a prognostic factor in plasma cell myeloma.

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7

Wang, Yan, Suxia Wang, and Youkang Zhang. "Proximal Tubulopathy of Monotypic Immunoglobulin Light Chain Restriction." Hong Kong Journal of Nephrology 17, no. 2 (2015): S71—S72. http://dx.doi.org/10.1016/j.hkjn.2015.09.043.

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8

Jasani, Bharat. "Immunohistologically definable light chain restriction in autoimmune disease." Journal of Pathology 154, no. 1 (1988): 1–5. http://dx.doi.org/10.1002/path.1711540102.

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9

Pollard, K. Michael, Voula Toumasatos, Louise Furphy, and John Webb. "Immunohistologically definable light chain restriction in autoimmune disease." Journal of Pathology 156, no. 4 (1988): 349–51. http://dx.doi.org/10.1002/path.1711560412.

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10

Baylis, Christine, James Falconer-Smith, and Brian Ross. "Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney." Clinical Science 74, no. 6 (1988): 639–44. http://dx.doi.org/10.1042/cs0740639.

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1. To examine the effect of charge and molecular size on the renal handling of immunoglobulin light chain, three different human light chains were purified, iodinated and characterized with regard to molecular weight and isoelectric point. The molecular weights were similar, whereas the isoelectric points ranged from markedly cationic to markedly anionic. 2. Renal handling of the light chains was determined in vivo in the Munich–Wistar rat and in vitro in the isolated perfused rat kidney. 3. Significant restriction to the transglomerular passage of all three light chains was evident in the intact kidney, with the most anionic light chain being restricted most while the cationic light chain was restricted least. The charge dependence of filtration of these naturally occurring proteins was, however, much less pronounced than has previously been reported for the synthetic dextrans. 4. Tubular reabsorption of the three light chains was quite variable in the intact kidney and did not appear to be related to molecular charge. In the isolated perfused kidney, once account had been taken of the abnormally high rate of filtration of these proteins, the reabsorption of the three light chains was strikingly similar to that seen in vivo. 5. With these three purified human light chains no marked influence of charge (pI) has been demonstrated in vivo or in vitro, for glomerular restriction or renal tubular reabsorption. Some other properties of human myeloma light chains may determine their renal handling and nephrotoxicity.

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11

Aravamudan, Bharathi, Caili Tong, Martha Q. Lacy, et al. "Immunoglobulin Variable Light Chain Restriction, Cytokine Expression and Plasma Cell-Stromal Cell Interactions in POEMS Syndrome Patients." Blood 112, no. 11 (2008): 2744. http://dx.doi.org/10.1182/blood.v112.11.2744.2744.

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Abstract POEMS syndrome is defined by the presence of peripheral neuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal protein expression (M), and skin changes (S). In addition, patients also have sclerotic bone lesions, papilledema, extravascular volume overload, thrombocytosis, and restrictive lung disease/pulmonary hypertension. A striking but inexplicable feature of the clonal plasma cells in patients with POEMS is that they are virtually always lambda restricted. More surprising is that of the 81 functional immunoglobulin light-chain variable-region genes (IgVL) available in the plasma cell/B cell repertoire, among the 13 cases in which variable gene light chain usage has been reported, all have been either IgVL1-40 or IgVL1-44. The molecular mechanisms triggering the initiation and the progression of POEMS syndrome or the clonal expansion of plasma cells marking this condition remain unclear. We have analyzed the immunoglobulin heavy and light chains sequences in the plasma cells of POEMS patients at the Mayo Clinic Rochester. We found that in 8 out of the 9 patients tested, we could document heavy chain clonality in any given patient; however, no restriction of gene usage among patients was observed in the variable regions of these chains. In the case of light chains, in 14 out of 17 patients we could document not only clonality but also restriction of light chain variable gene usage to IgVL1-40 or IgVL1-44. Our goal is to understand the relevance of this restricted expression of light chain variable region, and its effect on the communication between plasma cells and the neighboring stromal cells that might provide more insight into the disease pathology. To this end, we are generating viral vector constructs that will harbor the germline or mutant versions of IgVλ1-40 and IgVλ1-44 genes and introduced into pre-established malignant plasma cell lines (i.e. myeloma cell lines). We will assay the effects of this over expression in terms of alterations in the expression of cytokines such as VEGF and TNF, and on plasma cell-stromal cell interaction (in a co-culture system). Results from these assays will be discussed.

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12

Bapat, Kalyani, Dia Mansukhani, Shanaz Khodaiji, and Sachin Almel. "Acute Lymphoblastic Leukemia With Surface Light Chain Expression." Annals of Pathology and Laboratory Medicine 10, no. 5 (2023): C37–43. http://dx.doi.org/10.21276/apalm.3214.

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Acute Lymphoblastic leukemias (ALL) are a heterogeneous group of neoplasms which can either be having precursor B cell immunophenotype or mature B cell immunophenotype. Surface immunoglobulin light chain restriction is usually a feature of mature B cell neoplasms. A precursor B cell lymphoblastic leukemia (pre-B-ALL) with surface immunoglobulin light chain expression is a rare immunophenotype . We report a case of a 4 year old female with L1 type of blast morphology yet showing surface light chain restriction. Recognizing this rare immunophenotype and arriving at a correct diagnosis has therapeutic implications as treatment regimens differ for precursor B ALL as compared to mature B cell neoplasms.

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13

Munday, William R. "Russell body duodenitis with immunoglobulin kappa light chain restriction." World Journal of Gastrointestinal Endoscopy 7, no. 1 (2015): 73. http://dx.doi.org/10.4253/wjge.v7.i1.73.

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14

Boy, Sonja C., Marlene B. Van Heerden, Erich J. Raubenheimer, and Willie F. P. Van Heerden. "Plasmablastic lymphomas with light chain restriction - plasmablastic extramedullary plasmacytomas?" Journal of Oral Pathology & Medicine 39, no. 5 (2010): 435–39. http://dx.doi.org/10.1111/j.1600-0714.2009.00874.x.

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15

Elwyn, Lacey B., Angela Combs, Gabriel Villada, et al. "Localized Lichen Myxedematosus With Plasma Cell Light Chain Restriction." American Journal of Dermatopathology 41, no. 7 (2019): 505–10. http://dx.doi.org/10.1097/dad.0000000000001335.

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16

Owen-Casey, Mared P., Rosalind Sim, H. Terence Cook, et al. "Value of antibodies to free light chains in immunoperoxidase studies of renal biopsies." Journal of Clinical Pathology 67, no. 8 (2014): 661–66. http://dx.doi.org/10.1136/jclinpath-2014-202231.

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AimsBecause immunoglobulin abnormalities may affect the kidney, investigation of renal biopsies requires immunohistological study of light chains. A problem is that most antibodies to light chains react with whole immunoglobulins as well as free light chains, and there are generally many more whole immunoglobulins than free light chains. The usefulness of antibodies that only detected free light chains was investigated.MethodsAntibodies to free light chains were used in an immunoperoxidase method on paraffin sections of 198 renal biopsies, and compared with conventional antibodies against light chains examined by immunofluorescence on 13 frozen sections and by immunoperoxidase on 46 paraffin sections.ResultsImmunofluorescence and immunoperoxidase were concordant on 10 of 13 biopsies. Immunofluorescence detected slight deposition of light chains in three biopsies not shown by immunoperoxidase, of undetermined clinical significance. Using immunoperoxidase, the free light chain antibodies were more sensitive than conventional antibodies, giving much cleaner staining and better detection of deposits in AL amyloid, light chain deposition disease and cryoglobulinaemic glomerulonephritis. The free light chain antibodies showed discordance or ambiguity between immunohistological and clinical findings in seven (4%) of 185 patients with known immunoglobulin status. These included two of 28 cases of AL amyloid that showed no light chain deposition. The method was not designed for detection of light chain restriction in neoplastic plasma or lymphoplasmacytic cells.ConclusionsPolyclonal antibodies to free light chains are an improvement on conventional antibodies in immunoperoxidase study of paraffin sections of renal biopsies and are useful in everyday practice.

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17

Tanimoto, T., and Y. Ohtsuki. "T-cell-rich B-cell Lymphoma in a Pig." Veterinary Pathology 35, no. 2 (1998): 147–49. http://dx.doi.org/10.1177/030098589803500210.

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A case of multicentric lymphoma with a mixed cell population of large to small round cells with the same nuclear features in a pig was studied immunohistochemically. Neoplastic tissues were composed of 20–50% B-cell lymphoma cells with δ-type light chain restriction, and 50–80% cluster of differentiation (CD)3+ T-cells. These findings were similar to those of human T-cell-rich B-cell lymphoma (TCRBCL). In addition, both immunoglobulin IgM and IgG were detected in the cytoplasm of the identical lymphoma cell. This pattern of heavy chain expression appeared to be due to maturational arrest in cellular development at the point of heavy chain class switching, as occurs in biclonal gammopathy in human lymphoid malignancy. This case as TCRBCL containing two types of heavy chains with light chain restriction (IgM-δ and IgG-δ) appears to be the first of its kind reported in the English literature for either pigs or domestic animals.

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18

Lopez-Dee, Jennifer, Ronald Bowditch, and Robert McMillan. "Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP." Thrombosis and Haemostasis 85, no. 05 (2001): 821–23. http://dx.doi.org/10.1055/s-0037-1615754.

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SummaryChronic immune thrombocytopenic purpura is due to platelet destruction induced by autoantibodies against platelet surface antigens. Prior studies show that some serum autoantibodies are light-chain restricted, suggesting a clonal origin. Since plasma and platelet-associated antibody from the same patient may bind to different epitopes, it is important to evaluate the clonality of platelet-associated antibody. Platelet-associated autoantibodies from 28 ITP patients were studied. Of 23 platelet-associated antibodies tested directly, 16 showed significant light chain restriction (7 complete and 9 partial) when compared to plasma IgG light chain distribution. Similarly, 9 of 12 platelet-associated antibody eluates were light chain restricted, 5 complete and 4 partial. In all cases where platelet-associated antibody and antibody eluate from the same patient were studied, the results were concordant. We conclude that a significant proportion of platelet-associated antibodies from ITP patients show apparent clonality, as evaluated by light chain restriction. These results are consistent with other studies in ITP suggesting a limited antigenic repertoire.

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19

Sarwala, Sohini Parveen, Subhrajyoti Karmakar, and Keya Basu. "Unravelling the cardiac conundrum of amyloidosis: an experience from a tertiary care centre." International Journal of Research in Medical Sciences 13, no. 6 (2025): 2637–39. https://doi.org/10.18203/2320-6012.ijrms20251660.

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Amyloidosis encompasses a spectrum of diseases caused due to extracellular deposition of misfolded proteins in body. The most common subtypes that infiltrate cardiac tissue are AL, ATTRwt (wild type), ATTRv (mutated) and Isolated atrial amyloidosis. Here, we elaborate such an interesting case of cardiac AL amyloidosis. A 69-year-old male presented with shortness of breath and restrictive cardiomyopathy. Further endomyocardial biopsy showed acellular, light eosinophilic deposit. Direct immunofluorescence showed lambda light chain restriction, concordant with elevated serum free λ light chain level. Finally, positive Congo red stain with apple green birefringence under polarised light clinched the diagnosis of Cardiac AL Amyloidosis. Endomyocardial biopsy with congo red stain and immunofluorescence is indispensable for diagnosis and subtyping of AL amyloidosis. This sets apart other amyloid subtypes and cardiac light chain deposition disease. Early diagnosis of cardiac amyloidosis subtype is imperative to guide the therapy and evaluate the prognosis of the patient.

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20

Gujral, Sumeet, Nikhil Rabade, Asma Bibi, et al. "Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma." Indian Journal of Pathology and Microbiology 59, no. 3 (2016): 410. http://dx.doi.org/10.4103/0377-4929.188129.

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21

Kerim, Simonetta, Gigliola Reato, Cristina Abele, et al. "Immunoglobulin Light Chain Restriction and Clonal Rearrangement in Nodular Paragranuloma." Leukemia & Lymphoma 14, no. 5-6 (1994): 515–20. http://dx.doi.org/10.3109/10428199409049713.

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22

Kansal, Rina, George Deeb, Maurice Barcos, et al. "Precursor B Lymphoblastic Leukemia With Surface Light Chain Immunoglobulin Restriction." American Journal of Clinical Pathology 121, no. 4 (2004): 512–25. http://dx.doi.org/10.1309/wtxcq5nracvxtyby.

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23

Jasani, B. "Immunohistologically definable light chain restriction in autoimmune disease: Author's reply." Journal of Pathology 156, no. 4 (1988): 351–52. http://dx.doi.org/10.1002/path.1711560413.

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24

Furlan, Karina, Ira Miller, Brett Mahon, Fernando A. Ocampo Gonzalez, and Nicholas Ward. "Plasmablastic Lymphoma Associated with Adjacent Mature Plasma Cell Population Exhibiting Opposite Light Chain Restriction." Case Reports in Pathology 2020 (December 28, 2020): 1–9. http://dx.doi.org/10.1155/2020/8875547.

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Plasmablastic lymphoma (PBL) is an aggressive high-grade B cell lymphoma, considered a variant of diffuse large B cell lymphoma with approximately 75% mortality within 6-7 months. We describe an unusual case of PBL arising as a maxillary mass in an HIV-negative, nontransplanted 78-year-old female. Histologic examination revealed a diffuse infiltrate of anaplastic appearing cells exhibiting plasmablastic morphology with an adjacent contiguous infiltrate of mature appearing plasma cells. The PBL and mature plasma cell components both demonstrated an immunophenotype of CD20(-), CD38(+), and CD138(+). The two populations differed by the PBL featuring a high proliferation rate by Ki-67 (~95%) with coexpression of both c-MYC and EBV, while the mature plasma cell component featured a low proliferation rate by Ki-67 (~5%) without coexpression of c-MYC or EBV. Kappa/lambda staining demonstrated lambda light chain restriction involving the PBL, while the mature plasma cell infiltrate revealed kappa light chain restriction. Our findings describe the rare association of PBL with a synchronous distinct population of mature plasma cells exhibiting opposite light chain restriction.

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Kaur, Prabhjot, and Norman B. Levy. "Atypical marginal zone hyperplasia of tonsil with immunoglobulin light chain restriction." American Journal of Hematology 87, no. 4 (2011): 424–25. http://dx.doi.org/10.1002/ajh.22132.

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26

Cibeira, M. Teresa, José T. Ortiz-Pérez, Luis F. Quintana, Carlos Fernádez de Larrea, Natalia Tovar, and Joan Bladé. "Supportive Care in AL Amyloidosis." Acta Haematologica 143, no. 4 (2020): 335–42. http://dx.doi.org/10.1159/000506760.

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Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different organs. Prompt treatment directed to the underlying plasma cell clone is crucial in order to achieve a rapid, deep and durable hematologic response. The decrease in the production of the amyloidogenic light chains is a required condition to obtain the organ response, which is commonly delayed. Meanwhile, supportive treatment is aimed to maintain quality of life of these patients and preserve their involved organs’ function. From simple measures, such as salt restriction or compressive stockings, to very complex interventions, such as heart transplantation in very selected patients with isolated severe cardiac involvement, this supportive care is essential and has to be necessarily included in the multidisciplinary management of this disease.

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Xu, Dongsheng. "Dual Surface Immunoglobulin Light-Chain Expression in B-Cell Lymphoproliferative Disorders." Archives of Pathology & Laboratory Medicine 130, no. 6 (2006): 853–56. http://dx.doi.org/10.5858/2006-130-853-dsilei.

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Abstract Context.—Mature B lymphocytes exhibit allelic exclusion in which only a single class of immunoglobulin heavy chain and a single class of light chain, either κ or λ, are expressed. There have been several reports indicating that double light-chain gene rearrangements or dual light-chain expression can occur in B-cell malignant neoplasms, including chronic lymphocytic leukemia. Currently, it is a common notion that demonstration of light-chain restriction in a B-cell population is generally considered proof of monoclonality and indicates malignancy. Objective.—To increase awareness of the existence of the dual κ/λ immunoglobulin light-chain expressing B-cell leukemia/lymphoma, to emphasize the importance of visual inspection of flow cytometric data, and to present the guidelines for flow cytometric interpretation of dual κ/λ coexpressing populations. Data Sources.—Through comprehensive literature review, this article discusses the current understandings regarding the dual light-chain expression in B-cell neoplasms, the cellular and molecular mechanisms, and the clinical and diagnostic implications of dual light-chain expression. Conclusions.—Dual κ/λ light-chain expressing B-cell leukemia/lymphomas do exist. Recognition of the dual κ/ λ light-chain expression on B cells has diagnostic implication in leukemia/lymphoma immunophenotyping.

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Mercado, Juan Jose, James M. Markert, William Meador, Philip Chapman, Arie Perry, and James R. Hackney. "Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review." International Journal of Surgical Pathology 25, no. 8 (2017): 755–60. http://dx.doi.org/10.1177/1066896917717338.

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The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous “amyloid-like” material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red–negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

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Busto, P., R. Gerstein, L. Dupre, C. A. Giorgetti, E. Selsing, and J. L. Press. "Molecular analysis of heavy and light chains used by primary and secondary anti-(T,G)-A--L antibodies produced by normal and xid mice." Journal of Immunology 139, no. 2 (1987): 608–18. http://dx.doi.org/10.4049/jimmunol.139.2.608.

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Abstract The primary (1 degree) antibody response to (T,G)-A--L shows limited heterogeneity, consisting mostly of side chain-specific antibodies that bind GT and that express the TGB5 idiotype (Id). The secondary (2 degrees) response is very diverse: antibodies that bind the backbone A--L constitute a third of the response, and a high proportion of the side chain-specific antibodies do not bind GT and are TGB5 Id-. To provide a molecular basis for understanding this difference in repertoire expression, we analyzed the Ig genes used by heavy and light chains of 1 degree and 2 degrees side chain-specific anti-(T,G)-A--L hybridoma antibodies (HP). Southern blot restriction analysis and nucleotide sequence analysis of the expressed genes used by three TGB5 Id+ 2 degrees HP showed usage of three different VH genes in two VH gene families (36-60 and J558), different D segments, and two different Vk1 genes (the Vk1A and Vk1C subgroups). Thus, antibody heterogeneity in the 2 degrees response is contributed by combinatorial diversity of distinct germ-line genes. Nucleotide sequence analysis of the expressed genes used by TGB5 Id+ 1 degree HP showed use of highly homologous VH genes in the J558 VH gene family and highly homologous Vk1A genes. The majority of TGB5 Id+ 1 degree HP from different donors gave similar heavy and similar light chain gene rearrangements by Southern blot restriction analysis, after correction for known or potential J region differences. The combined nucleotide sequence and Southern blot restriction analysis data suggest that most 1 degree B cells use the same or very similar VH and Vk genes, i.e., the 1 degree response is paucigenic. Different D segments were used by the TGB5 Id+ 1 degree and 2 degrees HP that were sequenced, and there was no apparent correlation between TGB5 idiotypy and VH, D gene, or JH gene usage. However, all TGB5 Id+ HP sequenced used highly homologous genes from the Vk1 group. Expression of a Vk1 light chain correlates with, but is not sufficient for, TGB5 idiotypy, because one GT-binding, TGB5 Id- HP was found to use a Vk1C subgroup light chain. By Southern blot and nucleotide sequence analysis, the Vk genes used by two TGB5 Id+ 2 degrees HP from xid mice are highly homologous, if not identical to the Vk1A gene(s) used by 1 degree and 2 degrees Id+ HP from wild-type mice.

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30

Kudose, Satoru, Pietro Canetta, Nicole K. Andeen, et al. "Diagnostic Approach to Glomerulonephritis With Fibrillar IgG Deposits and Light Chain Restriction." Kidney International Reports 6, no. 4 (2021): 936–45. http://dx.doi.org/10.1016/j.ekir.2021.01.001.

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Thomas, Asha, Ram Prasad Elumalai, Barathi Gunabooshanam, Subalakshmi Balasubramanian, and Jayakumar Matcha. "Light chain proximal tubulopathy with lambda restriction presenting as acute kidney injury." Journal of Nephropathology 10, no. 3 (2021): e35-e35. http://dx.doi.org/10.34172/jnp.2021.35.

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32

Ratech, Howard, and Samuel Litwin. "Surface Immunoglobulin Light Chain Restriction in B-Cell Non-Hodgkin’s Malignant Lymphomas." American Journal of Clinical Pathology 91, no. 5 (1989): 583–86. http://dx.doi.org/10.1093/ajcp/91.5.583.

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33

Rosainz, Manuel Arana. "Acute B-Lymphoblastic Leukemia With Surface Immunoglobulin Light Chain Restriction: Case Report." American Journal of Clinical Pathology 150, suppl_1 (2018): S110. http://dx.doi.org/10.1093/ajcp/aqy097.266.

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34

Plaut, Joshua, Malcolm Galloway, Anna Childerhouse, and Robert Bradford. "Schwannoma with monoclonal plasma cell infiltration." Journal of Neurosurgery 111, no. 3 (2009): 509–11. http://dx.doi.org/10.3171/2009.3.17682.

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The authors report a very rare case of a vestibular schwannoma with an infiltrate of monoclonal plasma cells. A 45-year-old woman underwent routine excision of a presumed vestibular schwannoma. Histological analysis revealed the presence of a distinct lambda light chain restricted plasma cell population within the schwannoma. The light chain restriction and polymerase chain reaction–demonstrated monoclonality of the plasma cell population suggested the co-occurrence of a plasma cell neoplasm within a schwannoma. A search for systemic disease of plasma cell origin was unremarkable. A search of the literature suggests that this is the first report of such an occurrence.

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Hu, Yang, Mangju Wang, Yan Chen, et al. "The Significance Of Abnormal Plasma Cell Clone In Bone Marrow Of Primary Systemic Light Chain Amyloidosis Patients." Blood 122, no. 21 (2013): 5342. http://dx.doi.org/10.1182/blood.v122.21.5342.5342.

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Abstract In this study we analyzed the immunophenotype characteristics of the plasma cells and evaluated the significance of the abnormal plasma cell clone in bone marrow in primary systemic light chain amyloidosis (AL) patients. Fresh bone marrow samples were collected from 74 cases of plasma cell disease (PCD), including 51 cases of AL, 21 cases of multiple myeloma (MM), 2 cases of Waldenström's macroglobulinemia (WM). All patients diagnosed according to WHO 2008 diagnostic criteria. The diagnosis of AL was confirmed by the presence of monoclonal immunoglobulin or free light chain in blood or urine, and/or amyloidosis in fat tissues or biopsies by Congo red staining. Ten healthy donors were also collected as controls. Their clinical characteristics and immunophenotype of bone marrow cells were compared and analyzed. The immunophenotype were analyzed with a panel of antibodies including CD45, CD38, CD138, CD117, CD56, CD19, CD20, Igκ, Igλ, CD7, CD22, CD3, CD34 and CD27 by flow cytometry (FCM). The results were for statistical processing. The prominent feature of AL patients was multi-organ and multi-system involvement. Kidney was the major organ involvement (82.4%), followed by cardiovascular system (58.8%); MM mainly had the clinical manifestations of bone lesions (85.7%) and renal involvement (47.6%). The serum immunoglobulin of AL mainly manifested as λ light chain (74.5%), while the majority of MM manifested as κ (61.9%). In the 51 patients of AL, the ratio of plasma cellsin bone marrow was mean 3.87% (0.17∼9.34%) by FCM, and 4.47% (0∼14.5%) by morphological examination. In MM, the ratio of plasma cells was mean 13.17% (1.30∼48.91%) by FCM and 33.55% (3.0∼81.5%) by morphological examination. The plasma cells proportion between AL and MM had significant difference (P< 0.05). The κ or λ light chain restriction can be used for the detection of abnormal plasma cell clones in AL patients. The κ/λ ratio>4.0 or <0.5 can be used as the criteria to identify light chain restriction in plasma cells in AL patients. The 31/51 cases of AL could detected abnormal plasma cell clone that used κ/λ light chain restriction and were mainly expressed λ light chain (24/31, 77.4%). The 21 cases of MM had light chain restriction, mainly expressed κ light chain (13/21, 61.9%) (P<0.05). In CD45/SSC scattergram, the position of abnormal plasma cells of AL patients varied in a wider range. According to the features of CD38+/CD138+ as the basic markers for plasma cells, abnormal plasma cells were CD45 negative or weak positive in AL patients, similar to the CD45 level distribution in malignant plasma cells in MM. In WM, the proliferated cells were plasmacytoid lymphocytes with CD45 weakly or strong positive. FCM can identify abnormal plasma cell clone in bone marrow of AL patients. In 51cases of AL, 78.4% of bone marrow plasma cells were CD56+, 68.6% were CD117+, and 88.2% were CD19-. In 21 of MM, 66.7% were CD56+, 38.1% were CD117+, and 90.4% were CD19-. These results manifested significant difference compared with those of normal plasma cells (P< 0.05). In 2 cases of WM, these plasmacytoid lymphocytes were CD19+ and CD56-, CD117-.The ratios of CD56+, CD117+, CD19-, and CD45-/dim in bone marrow plasma cells were significantly higher in AL patients than in WM patients and healthy individuals (P<0.05), but were similar to those in MM patients (P>0.05). The main difference between AL and MM was the larger size of plasma cell group in MM (P＜0.05). In summary, according to light chain restricted expression and abnormal immunephenotype by FCM analysis we can determine abnormal plasma cell clone in bone marrow of AL patients and the abnormal plasma cells clone can be used as an important diagnostic marker of AL. Disclosures: No relevant conflicts of interest to declare.

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Watkins, B. A., A. E. Davis, S. Fiorentini, F. di Marzo Veronese, and M. S. Reitz. "Evidence for distinct contributions of heavy and light chains to restriction of antibody recognition of the HIV-1 principal neutralization determinant." Journal of Immunology 156, no. 4 (1996): 1676–83. http://dx.doi.org/10.4049/jimmunol.156.4.1676.

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Abstract We have used phage Ab display technology to analyze two mAbs to HIV-1 envelope proteins gp120 and gp41. From the data obtained we are able to demonstrate that the recognition of the principal neutralization determinant of different strains of HIV-1 by neutralizing mAb M77 is restricted by its heavy and light chains in different ways. Native M77 is able to recognize and neutralize HIV-1 strain IIIB through binding to the gp120 V3 loop. M77 is unable to recognize strains of HIV-1 that differ on either the left or right side of the V3 loop tip. A chain-switched Fab fragment containing the M77 Fd fragment and a different light chain was able to recognize HIV-1 strains that differ from IIIB on the left side but not the right side of the V3 loop tip.

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Bayer-Garner, Ilene B., Victor G. Prieto та Bruce R. Smoller. "Detection of Clonality With κ and λ Immunohistochemical Analysis in Cutaneous Plasmacytomas". Archives of Pathology & Laboratory Medicine 128, № 6 (2004): 645–48. http://dx.doi.org/10.5858/2004-128-645-docwai.

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Abstract Context.—Cutaneous plasmacytomas rarely occur in the setting of multiple myeloma. However, since poorly differentiated lesions may resemble other neoplasms, such as carcinoma, melanoma, and lymphoma, the diagnosis of cutaneous plasmacytoma may be difficult. Objective.—To demonstrate clonality using κ and λ immunohistochemical analysis in cutaneous plasmacytomas and to ascertain whether or not interpretation is hindered by background staining. Design.—Pathology reports of all patients with the diagnosis of multiple myeloma were reviewed. Twelve patients had cutaneous lesions diagnosed as plasmacytoma, and these lesions were analyzed for light chain restriction with κ and λ immunohistochemical analysis. Results.—In most cases (11 of 12), monoclonality was demonstrated. In the remaining case, monoclonality could not be established because most cells did not stain for either κ or λ. Conclusions.—Light chain restriction can be demonstrated in most multiple myeloma–related cutaneous plasmacytomas, establishing the neoplastic nature of the infiltrate.

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Martinez-Lopez, Azahara, Santiago Montes-Moreno, Rafael Ramos, et al. "Childhood florid follicular hyperplasia with immunoglobulin light-chain restriction in the gastrointestinal tract." Histopathology 65, no. 6 (2014): 805–13. http://dx.doi.org/10.1111/his.12511.

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Tomita, Naoto, Kengo Takeuchi, Rie Hyo, et al. "Diffuse Large B Cell Lymphoma without Immunoglobulin Light Chain Restriction by Flow Cytometry." Acta Haematologica 121, no. 4 (2009): 196–201. http://dx.doi.org/10.1159/000220332.

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Ramavajula, Anitha, Manisha sahay, and Swarnalata Gowri shankar. "WCN25-3575 A rare case of MGRS – PGNMID with light chain restriction only." Kidney International Reports 10, no. 2 (2025): S224—S225. https://doi.org/10.1016/j.ekir.2024.11.431.

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41

Zhang, Linsheng, Sally E. Self, and John Lazarchick. "Detection of Minimal Residual Disease of Plasma Cell Myeloma by Five Color Flow Cytometric Immunophenotype Analysis." Blood 116, no. 21 (2010): 1903. http://dx.doi.org/10.1182/blood.v116.21.1903.1903.

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Abstract Abstract 1903 Flow cytometry is widely used to identify a monoclonal proliferation of plasma cells through cytoplasmic immunoglobulin light chain analysis, with a better sensitivity than immunocytochemical staining. Recent studies have demonstrated that neoplastic plasma cells express aberrant surface antigens and immunophenotyping of plasma cells by multiparameter flow cytometry is able to reveal neoplastic plasma cells by their surface antigen profile to a level that is meaningful for the detection of prognostically relevant minimal residual disease. In this study, we compare the sensitivity of detecting abnormal plasma cells by five color flow cytometric immunophenotyping and concurrent cytoplasmic immunoglobulin light chain analysis. Multiparameter analysis was performed with cell surface markers CD45, CD38, CD138, CD19, CD20, CD56, CD117, CD27 and CD28. Plasma cells were identified by bright CD38 and CD138 expression. The bone marrow plasma cells from 8 newly diagnosed or recurrent plasma cell myelomas with 10% or more morphologically identifiable plasma cells were initially analyzed. At least one antigen was found to be abnormally expressed in all 8 cases. CD45, CD19, CD56 and CD117 were most useful in recognizing abnormal plasma cells. Both CD45 and CD19 were negative in all 8 cases. CD56 and CD117 were each positive in 6 cases; at least one of them was positive in all 8 cases; and 4 cases co-expressed both antigens. Thirteen additional cases of plasma cell myeloma in clinical remission with less than 10% plasma cells by bone marrow morphology were studied with antibodies to CD38, CD138, CD45, CD56 and CD117 in a single tube. Eleven cases revealed an abnormal immunophenotype, however, immunoglobulin light chain restriction was detected only in 6 cases. Two cases demonstrated normal phenotype and did not show immunoglobulin light chain restriction. Immunoglobulin light chain restriction was not demonstrated in any cases with less than 0.5% bright CD38 plasma cells. In one case with 9% plasma cells by morphologic examination, the immunoglobulin light chain analysis failed to reveal monoclonal proliferation whereas abnormal expression of both CD56 and CD117 was identified in 50% of the bright CD38 and CD138 positive plasma cells, although flow cytometry only detected a total of 0.5% plasma cells. Abnormal phenotype was detected at a level as low as 0.05% plasma cells by flowcytometry, in cases that less than 1% plasma cells were identified by morphologic examination. Our result suggests that 5 color flow cytometric immunophenotyping is a sensitive and practical way to detect minimal residual disease of plasma cell myeloma in patients under clinical remission. Because rare neoplastic plasma cells may not have abnormal surface antigen profile, and the abnormal phenotype may change after chemotherapy, combination with cytoplasmic immunoglobulin light chain analysis may be necessary to increase the sensitivity and specificity. Disclosures: No relevant conflicts of interest to declare.

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Newkirk, M. M., R. A. Mageed, R. Jefferis, P. P. Chen, and J. D. Capra. "Complete amino acid sequences of variable regions of two human IgM rheumatoid factors, BOR and KAS of the Wa idiotypic family, reveal restricted use of heavy and light chain variable and joining region gene segments." Journal of Experimental Medicine 166, no. 2 (1987): 550–64. http://dx.doi.org/10.1084/jem.166.2.550.

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Evidence derived from the complete amino acid sequences of the variable regions of both the heavy and light chains of two members (BOR and KAS) of the Wa idiotypic family of human rheumatoid factors suggests that not only are the light chains of these molecules derived from possibly one variable region gene segment, but the heavy chain variable regions are all derived from the VHI subgroup of human V region genes. These molecules exhibit a surprising conservation in the size of D region, and all use the JH4 gene element. This restriction in use of VL, VH, D, and JH suggests all of these elements may play a crucial role in either antigen binding and/or expression of the crossreactive idiotype.

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Franklin, Michael, Chelsey Deel, and Mohammad Vasef. "Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chain mRNA in Marginal Zone Lymphoma Demonstrates Comparable Performance to Flow Cytometry." American Journal of Clinical Pathology 152, Supplement_1 (2019): S109. http://dx.doi.org/10.1093/ajcp/aqz121.011.

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Abstract Objectives Evaluation of light chain restriction is critical to establish clonality in B-cell lymphoproliferative disorders (LPDs). Immunohistochemistry (IHC) and in situ hybridization (ISH) are commonly used to assess light chain restriction in formalin-fixed, paraffin-embedded (FFPE) tissues. However, except for cases with plasma cell differentiation, these techniques often fail to identify immunoglobulin light chains. An ultrasensitive technique, RNAscope, has been recently introduced that can identify light chains in cases of B-cell LPDs. We analyzed the utility of this ultrasensitive method in detection of clonality and correlated with flow cytometry results when available. Methods A tissue microarray was constructed using 1.6-mm diameter tissue punches of 31 FFPE tissue blocks from 27 cases that were previously characterized as marginal zone lymphoma (MZL) by a combination of morphology, IHC, and/or flow cytometry. Cases included 8 nodal and 19 extranodal MZLs. In two cases, additional blocks were included to assess reproducibility. For ultrasensitive ISH RNAscope assay, 4-µm thickness tissue sections were hybridized using kappa and lambda probes, incubated overnight, counterstained with hematoxylin, cover-slipped, and reviewed blindly without knowledge of prior flow cytometry results. Results Of 18 cases with evaluable staining, 15 were clonal and 3 were polytypic. Flow cytometry was available in 14 of these 18 cases with concordance in 13 of 14 (93%). The discordant case was polytypic by flow cytometry but kappa restricted by RNAscope. The false-negative flow results could be due to sampling issues. In six cases, staining failed and could not be evaluated. Conclusion Ultrasensitive RNAscope is a reliable assay in the detection of clonality in FFPE tissue, particularly where fresh tissue is not available for flow cytometry. In addition, our results confirm and further expand prior observations that RNAscope is a highly sensitive and specific assay with high concordance with flow cytometry.

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Fischer, Edgar G., Thèrése J. Bocklage, Ian Rabinowitz, Harriet O. Smith, and David S. Viswanatha. "Primary Plasmacytoma Arising in an Endocervical Polyp With Detection of Neoplastic Cells on Papanicolaou Test." Archives of Pathology & Laboratory Medicine 127, no. 1 (2003): e28-e31. http://dx.doi.org/10.5858/2003-127-e28-ppaiae.

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Abstract Primary plasmacytomas of the female genital tract are extremely rare and present a substantial diagnostic challenge. Five cases morphologically representing plasmacytomas and localized to the uterine cervix have been reported previously; however, only 1 was shown to be monotypic for immunoglobulin light-chain expression. We report the case of a 37-year-old woman who had highly atypical plasma cells on her Papanicolaou test. A clinically detected endocervical polyp was removed and revealed a plasmacytoma, the diagnosis of which was substantiated by demonstrating monotypic λ-light-chain restriction and a clonal immunoglobulin heavy-chain gene rearrangement. The cytologic and histopathologic findings of plasmacytomas of the uterine cervix are discussed, including the utility of immunophenotypic and molecular techniques to confirm the neoplastic diagnosis.

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Roark, Jessica H., James B. Bussel, Douglas B. Cines, and Don L. Siegel. "Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation." Blood 100, no. 4 (2002): 1388–98. http://dx.doi.org/10.1182/blood.v100.4.1388.h81602001388_1388_1398.

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Although idiopathic thrombocytopenic purpura (ITP) is the most common autoimmune hematologic disorder, little is known about the associated autoantibodies on a molecular level. Consequently, diagnostic assays and therapy for ITP lack specificity. To avoid technical limitations imposed by B-cell immortalization methods, we used repertoire cloning (Fab/phage display) to clone platelet autoantibodies and examine the relation between immunoglobulin (Ig) gene usage, clonality, and antigen specificity. Phage display libraries were constructed from splenocytes from 2 patients with chronic ITP, and competitive cell-surface selection was used to isolate several dozen unique IgG platelet-specific autoantibodies. Platelet-reactive Fabs in both patients were associated almost exclusively with rearrangements of a single Ig heavy-chain variable-region gene (VH3-30), despite an apparent diversity of antigen specificities. Comparative analysis of platelet-reactive Fab Ig gene rearrangements from each patient suggested that they evolved from a restricted number of B-cell clones through somatic mutation with high replacement-to-silent mutation ratios. Although VH3-30–encoded heavy chains were found with light chains encoded by several different Ig genes, molecular repairing experiments showed exquisite restriction on the specific heavy- and light-chain pairings that permitted platelet reactivity. Together, these data suggest that the development of platelet-reactive antibodies associated with ITP is driven by an encounter with diverse platelet antigens through the clonal expansion of B cells using genetically restricted and highly specific combinations of heavy- and light-chain gene products. The extraordinarily high usage of the VH3-30 heavy-chain gene in these patients has implications for the pathogenesis, diagnosis, and management of chronic ITP.

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Yao, Ying, Su-Xia Wang, You-Kang Zhang, Yan Wang, Li Liu, and Gang Liu. "Acquired Fanconi Syndrome with Proximal Tubular Cytoplasmic Fibrillary Inclusions of ^|^lambda; Light Chain Restriction." Internal Medicine 53, no. 2 (2014): 121–24. http://dx.doi.org/10.2169/internalmedicine.53.0836.

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Chen, Peter P., Christopher A. Tormey, Stephanie C. Eisenbarth, et al. "False-Positive Light Chain Clonal Restriction by Flow Cytometry in Patients Treated With Alemtuzumab." American Journal of Clinical Pathology 151, no. 2 (2018): 154–63. http://dx.doi.org/10.1093/ajcp/aqy129.

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Zhang, Hejun, Zhu Jin, and Rongli Cui. "Russell body gastritis/duodenitis: A case series and description of immunoglobulin light chain restriction." Clinics and Research in Hepatology and Gastroenterology 38, no. 5 (2014): e89-e97. http://dx.doi.org/10.1016/j.clinre.2014.05.008.

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Erickson, K. M., and D. Lynch. "Concomitant Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Discovered by Flow Cytometry." American Journal of Clinical Pathology 154, Supplement_1 (2020): S23. http://dx.doi.org/10.1093/ajcp/aqaa161.043.

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Abstract Casestudy: Chronic lymphocytic leukemia (CLL) accounts for about 30% of all lymphoid neoplasms and is the most common adult blood cancer in the Western world. Mantle cell lymphoma (MCL) accounts for only about 6% of all B-cell lymphomas in Western countries. MCL and CLL are both CD5 positive B-cell lymphoproliferative disorders. It is necessary to distinguish these two entities as MCL is a more aggressive disease, and requires specific treatment. MCL and CLL can occur in one patient at the same time and is often termed a composite lymphoma. We present an 84-year-old female with a history of endometrial cancer who was found to have splenomegaly and lymphadenopathy. Flow cytometry was performed upon her peripheral blood specimen which demonstrated two distinct populations of abnormal light chain restricted B-cell populations. One population demonstrated kappa light chain restriction and was positive for CD45, CD19, CD20, CD5, CD38, FMC-7, and CD22, representing MCL. The other population showed dim lambda light chain restriction that was also positive for CD45, CD19, dim CD20, CD5, and CD23, representing CLL. FISH studies demonstrated t(11;14), and four common deletions or chromosome aneuploidy associated with CLL. These findings confirmed the dual populations of CLL and MCL. This is an interesting case because it is a very rare combination with only a few cases having been reported with two distinct cell populations in one patient at the same time.

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Erickson, K. M., and D. Lynch. "Concomitant Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Discovered by Flow Cytometry." American Journal of Clinical Pathology 154, Supplement_1 (2020): S127. http://dx.doi.org/10.1093/ajcp/aqaa161.278.

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Abstract Casestudy: Chronic lymphocytic leukemia (CLL) accounts for about 30% of all lymphoid neoplasms and is the most common adult blood cancer in the Western world. Mantle cell lymphoma (MCL) accounts for only about 6% of all B-cell lymphomas in Western countries. MCL and CLL are both CD5 positive B-cell lymphoproliferative disorders. It is necessary to distinguish these two entities as MCL is a more aggressive disease, and requires specific treatment. MCL and CLL can occur in one patient at the same time and is often termed a composite lymphoma. We present an 84-year-old female with a history of endometrial cancer who was found to have splenomegaly and lymphadenopathy. Flow cytometry was performed upon her peripheral blood specimen which demonstrated two distinct populations of abnormal light chain restricted B-cell populations. One population demonstrated kappa light chain restriction and was positive for CD45, CD19, CD20, CD5, CD38, FMC-7, and CD22, representing MCL. The other population showed dim lambda light chain restriction that was also positive for CD45, CD19, dim CD20, CD5, and CD23, representing CLL. FISH studies demonstrated t(11;14), and four common deletions or chromosome aneuploidy associated with CLL. These findings confirmed the dual populations of CLL and MCL. This is an interesting case because it is a very rare combination with only a few cases having been reported with two distinct cell populations in one patient at the same time.

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