Genomes and Genes
immunoglobulin light chains
Summary: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
- Schoettler N, Ni D, Weigert M. B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients. Mol Immunol. 2012;51:273-82 pubmed publisher..Our data shows that V(L) gene expression is variable and supports a model where the L-chain repertoire is generated by both positive and negative selection on L-chains. ..
- Pantazis G, Psaras T, Krope K, von Coelln R, Fend F, Bock T, et al. Cerebral low-grade lymphoma and light chain deposition disease: exceedingly high IgG levels in the cerebrospinal fluid as a diagnostic clue. Clin Neuropathol. 2010;29:378-83 pubmed..In constellations of highly elevated IgG in CSF and multiple white matter lesions, LCDD should be considered as underlying pathology. ..
- Fujita H, Hishizawa M, Sakamoto S, Kondo T, Kadowaki N, Ishikawa T, et al. Durable hematological response and improvement of nephrotic syndrome on thalidomide therapy in a patient with refractory light chain deposition disease. Int J Hematol. 2011;93:673-676 pubmed publisher..Based on the renal biopsy findings and the presence of monoclonal immunoglobulin light chains in her serum and urine, LCDD was diagnosed...
- Kalinina O, Doyle Cooper C, Miksanek J, Meng W, Prak E, Weigert M. Alternative mechanisms of receptor editing in autoreactive B cells. Proc Natl Acad Sci U S A. 2011;108:7125-30 pubmed publisher..The editing mechanisms in the case of ?-expressing B cells include L chain allelic inclusion and V(H) replacement. ..
- Smirnov I, Carletti E, Kurkova I, Nachon F, Nicolet Y, Mitkevich V, et al. Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics. Proc Natl Acad Sci U S A. 2011;108:15954-9 pubmed publisher..The organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate-limiting dephosphorylation. This reactibody is, therefore, a kinetically selected protein template that has enzyme-like catalytic attributes. ..
- Blancas Mejia L, Ramirez Alvarado M. Systemic amyloidoses. Annu Rev Biochem. 2013;82:745-74 pubmed publisher..We also review current cellular, tissue, and animal models and discuss the challenges and opportunities for future studies of the systemic amyloidoses. ..
- Jimenez Zepeda V. Light chain deposition disease: novel biological insights and treatment advances. Int J Lab Hematol. 2012;34:347-55 pubmed publisher..chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of immunoglobulin light chains in various organs...
- Kumar S, Dispenzieri A, Lacy M, Hayman S, Buadi F, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989-95 pubmed publisher..Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis. ..
- Chailyan A, Marcatili P, Tramontano A. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity. FEBS J. 2011;278:2858-66 pubmed publisher..We also show that the different packing modes are related to the type of recognized antigen. ..
- Scheid J, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira T, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011;333:1633-7 pubmed publisher..Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike. ..
- Dicostanzo A, Thompson J, Peterson F, Volkman B, Ramirez Alvarado M. Tyrosine residues mediate fibril formation in a dynamic light chain dimer interface. J Biol Chem. 2012;287:27997-8006 pubmed publisherLight chain amyloidosis is an incurable protein misfolding disease where monoclonal immunoglobulin light chains misfold and deposit as amyloid fibrils, causing organ failure and death...
- Gagnon P, Rodriquez G, Zaidi S. Dissociation and fractionation of heavy and light chains from IgG monoclonal antibodies. J Chromatogr A. 2011;1218:2402-4 pubmed publisher..Significant scope remains to refine the conditions. The method can be applied to other disulfide bonded proteins with significant affinity for cation exchangers. ..
- Li M, Wu Y, Qiu Y, Yao Z, Liu S, Liu Y, et al. 2A peptide-based, lentivirus-mediated anti-death receptor 5 chimeric antibody expression prevents tumor growth in nude mice. Mol Ther. 2012;20:46-53 pubmed publisher..These data suggest that lentivirus-mediated, 2A peptide-based anti-DR5 chimeric antibody expression may have clinical utility as an anticancer treatment and may represent a rational adjuvant therapy in combination with chemotherapy. ..
- Perfetti V, Palladini G, Casarini S, Navazza V, Rognoni P, Obici L, et al. The repertoire of ? light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44. Blood. 2012;119:144-50 pubmed publisher..Study of the characteristics of IGVL1-44-LC with, and of the minority without, heart involvement might lead to identification of LC/tissue interactions. ..
- Paiva B, Martinez Lopez J, Vidriales M, Mateos M, Montalban M, Fernandez Redondo E, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol. 2011;29:1627-33 pubmed publisher..Achieving an IR translates into superior PFS and TTP compared with conventional CR or stringent CR. These techniques provide complementary information and thus, an effort should be made to refine response criteria in MM. ..
- Dimopoulos M, Kyle R, Fermand J, Rajkumar S, San Miguel J, Chanan Khan A, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117:4701-5 pubmed publisher..The skeletal survey remains the standard method for imaging screening, but magnetic resonance imaging frequently provides valuable diagnostic and prognostic information. Most of these tests are repeated during follow-up or at relapse. ..
- Jayaram N, Bhowmick P, Martin A. Germline VH/VL pairing in antibodies. Protein Eng Des Sel. 2012;25:523-9 pubmed..The closest equivalent human and mouse gene families were identified and pairing preferences compared. This work may impact on the ability to generate more stable antibodies for use as biopharmaceuticals. ..
- Levinson R, Olatoye O, Randles E, Howell K, Dicostanzo A, Ramirez Alvarado M. Role of mutations in the cellular internalization of amyloidogenic light chains into cardiomyocytes. Sci Rep. 2013;3:1278 pubmed publisherLight chain (AL) amyloidosis is characterized by the misfolding of immunoglobulin light chains, accumulating as amyloid fibrils in vital organs...
- Tiller T, Meffre E, Yurasov S, Tsuiji M, Nussenzweig M, Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods. 2008;329:112-24 pubmed
- van Rhee F, Bolejack V, Hollmig K, Pineda Roman M, Anaissie E, Epstein J, et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood. 2007;110:827-32 pubmed..65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival. ..
- Sanchorawala V. Light-chain (AL) amyloidosis: diagnosis and treatment. Clin J Am Soc Nephrol. 2006;1:1331-41 pubmed..This review outlines approaches to diagnosis, assessment of disease severity, and treatment of AL amyloidosis. ..
- Dispenzieri A, Kyle R, Katzmann J, Therneau T, Larson D, Benson J, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008;111:785-9 pubmedWe hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering multiple myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active ..
- Prokaeva T, Spencer B, Kaut M, Ozonoff A, Doros G, Connors L, et al. Soft tissue, joint, and bone manifestations of AL amyloidosis: clinical presentation, molecular features, and survival. Arthritis Rheum. 2007;56:3858-68 pubmed
- Matsumori A, Shimada M, Jie X, Higuchi H, Groot Kormelink T, Redegeld F. Effects of free immunoglobulin light chains on viral myocarditis. Circ Res. 2010;106:1533-40 pubmed publisher..Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation...
- Narayanan A, Sellers B, Jacobson M. Energy-based analysis and prediction of the orientation between light- and heavy-chain antibody variable domains. J Mol Biol. 2009;388:941-53 pubmed publisher..When applied to antibody homology models generated from templates with 55-75% sequence identity, we predict the V(L):V(H) orientation of 20 antibodies with an average/median RMSD of 2.1/1.6 A to the crystal structures. ..
- Bodi K, Prokaeva T, Spencer B, Eberhard M, Connors L, Seldin D. AL-Base: a visual platform analysis tool for the study of amyloidogenic immunoglobulin light chain sequences. Amyloid. 2009;16:1-8 pubmed publisher..The likelihood that each sequence has evolved through somatic hypermutation can be predicted using an automated binomial or multinomial distribution model. AL-Base is available to the scientific community for research purposes. ..
- Sengul S, Li M, Batuman V. Myeloma kidney: toward its prevention--with new insights from in vitro and in vivo models of renal injury. J Nephrol. 2009;22:17-28 pubmed..Further clinical studies are necessary to establish the usefulness of these novel therapies in preserving the kidney function in patients with multiple myeloma. ..
- Das S, Nikolaidis N, Klein J, Nei M. Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers. Proc Natl Acad Sci U S A. 2008;105:16647-52 pubmed publisher..These rearrangements have resulted in interspecific variation of the genomic lengths of the IGL loci and the number and order of IGL constituent genes, but the overall organization of the IGL loci has not changed. ..
- Nieva J, Shafton A, Altobell L, Tripuraneni S, Rogel J, Wentworth A, et al. Lipid-derived aldehydes accelerate light chain amyloid and amorphous aggregation. Biochemistry. 2008;47:7695-705 pubmed publisher..Given these data, we feel our recently discovered paradigm of inflammatory aldehyde-induced protein misfolding may now extend to LC aggregation. ..
- Terrier B, Sene D, Saadoun D, Ghillani Dalbin P, Thibault V, Delluc A, et al. Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders. Ann Rheum Dis. 2009;68:89-93 pubmed publisher..After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation. ..
- Gertz M, Lacy M, Dispenzieri A, Hayman S, Kumar S, Dingli D, et al. Autologous stem cell transplant for immunoglobulin light chain amyloidosis: a status report. Leuk Lymphoma. 2010;51:2181-7 pubmed publisher..001). The only predictor of survival was cardiac stage (p ?<?0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival. ..
- Sanchorawala V, Skinner M, Quillen K, Finn K, Doros G, Seldin D. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation. Blood. 2007;110:3561-3 pubmed..001). In conclusion, HDM/SCT leads to durable remissions and prolonged survival, particularly for those patients who achieve a hematologic CR. ..
- Kim Y, Kim J, Lee S, Lee W, Sohn J, Chung Y, et al. Heavy and light chain variable single domains of an anti-DNA binding antibody hydrolyze both double- and single-stranded DNAs without sequence specificity. J Biol Chem. 2006;281:15287-95 pubmed..Our results demonstrate single domain Abs with DNase activities for the first time, which might provide new insights into substrate recognition and catalytic mechanisms of anti-DNA Abs. ..
- McLaughlin R, De Stigter J, Sikkink L, Baden E, Ramirez Alvarado M. The effects of sodium sulfate, glycosaminoglycans, and Congo red on the structure, stability, and amyloid formation of an immunoglobulin light-chain protein. Protein Sci. 2006;15:1710-22 pubmed..This paper provides insight into the impact of different reagents on light-chain stability, structure, amyloid fibril formation, and inhibition. ..
- Doyle C, Han J, Weigert M, Prak E. Consequences of receptor editing at the lambda locus: multireactivity and light chain secretion. Proc Natl Acad Sci U S A. 2006;103:11264-9 pubmed..These clones may represent products of exhaustive rearrangement. Multireactivity, allelic inclusion, and L chain secretion are three consequences of editing at the lambda locus that may predispose toward the development of autoimmunity. ..
- Herzog S, Reth M, Jumaa H. Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nat Rev Immunol. 2009;9:195-205 pubmed publisher..In this Review, we discuss how FOXO transcription factors are regulated by the pre-BCR to allow the progression of the cell cycle and the recombination of the light chain gene. ..
- Gertz M, Zeldenrust S. Treatment of immunoglobulin light chain amyloidosis. Curr Hematol Malig Rep. 2009;4:91-8 pubmed publisher..Virtually all patients are candidates for a trial of therapy, and it is possible to find a nontoxic regimen that can be administered to virtually any patient. ..
- Basnayake K, Ying W, Wang P, Sanders P. Immunoglobulin light chains activate tubular epithelial cells through redox signaling. J Am Soc Nephrol. 2010;21:1165-73 pubmed publisher..These data show that intracellular H(2)O(2) induced by endocytosis of monoclonal free light chains oxidizes and activates c-Src, which promotes release of MCP-1. ..
- Kormelink T, Tekstra J, Thurlings R, Boumans M, Vos K, Tak P, et al. Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis. 2010;69:2137-44 pubmed publisher..The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of RA. ..
- Schouten B, van Esch B, van Thuijl A, Blokhuis B, Groot Kormelink T, Hofman G, et al. Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins. J Allergy Clin Immunol. 2010;125:1308-14 pubmed publisher..Also, in children affected with CMA or AD, serum Ig-fLC concentrations were increased, implying the relevance of Ig-fLC measurements in the diagnoses of human allergic disease. ..
- Hutchison C, Cockwell P, Harding S, Mead G, Bradwell A, Barnett A. Quantitative assessment of serum and urinary polyclonal free light chains in patients with type II diabetes: an early marker of diabetic kidney disease?. Expert Opin Ther Targets. 2008;12:667-76 pubmed..These novel findings provide the basis for future studies to assess whether polyclonal FLCs could provide a useful tool for early diagnosis of diabetic kidney disease. ..
- Sikkink L, Ramirez Alvarado M. Salts enhance both protein stability and amyloid formation of an immunoglobulin light chain. Biophys Chem. 2008;135:25-31 pubmed publisher..Our study emphasizes the importance of the effect of ions in the protein bound water properties and downplays the role of specific interactions between the protein and ions. ..
- Palladini G, Lavatelli F, Russo P, Perlini S, Perfetti V, Bosoni T, et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood. 2006;107:3854-8 pubmed..Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography. ..
- Qin T, Ren L, Hu X, Guo Y, Fei J, Zhu Q, et al. Genomic organization of the immunoglobulin light chain gene loci in Xenopus tropicalis: evolutionary implications. Dev Comp Immunol. 2008;32:156-65 pubmed
- Kalwy S, Rance J, Young R. Toward more efficient protein expression: keep the message simple. Mol Biotechnol. 2006;34:151-6 pubmed..Our findings suggest that significant improvements in product yields can be achieved by gene optimization, which may facilitate the processing and translation of gene transcripts. ..
- Paik S, Kim S, Kim J, Yang W, Lee Y. Russell body gastritis associated with Helicobacter pylori infection: a case report. J Clin Pathol. 2006;59:1316-9 pubmed..appearance is easily confirmed to be non-neoplastic by its polyclonal immunoreactive pattern to immunoglobulin light chains. However, the aetiology of Russell body gastritis is controversial and hence the optimal treatment for ..
- Batuman V. Proximal tubular injury in myeloma. Contrib Nephrol. 2007;153:87-104 pubmed..These proximal tubule alterations often progress to a severe tubulointerstitial kidney disease, the most common type of kidney involvement responsible for endstage renal failure seen in myeloma patients. ..
- Sanchorawala V, Wright D, Rosenzweig M, Finn K, Fennessey S, Zeldis J, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007;109:492-6 pubmedIn immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal plasma cell dyscrasia accumulate in tissues and damage vital organs...
- Kostareli E, Sutton L, Hadzidimitriou A, Darzentas N, Kouvatsi A, Tsaftaris A, et al. Intraclonal diversification of immunoglobulin light chains in a subset of chronic lymphocytic leukemia alludes to antigen-driven clonal evolution. Leukemia. 2010;24:1317-24 pubmed publisher..Furthermore, they strongly suggest that light chains have an active role in the antigen selection process, at least for certain subsets of CLL cases. ..