Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease.

Cogné, Michel; Preud’homme, Jean-Louis; Bauwens, Marc; Touchard, Guy; Aucouturier, Pièrre

doi:10.1172/jci115252

Cited by 84 publications

(58 citation statements)

References 38 publications

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“…and when deposited, truncated heavy chains), in such a case, we recently demonstrated that the LC produced hy the hone marrow cells and that found in the tissue deposits were identical and hore several point mutations in the V.-J^ region, one of which resulted in Nglycosylation (at position +70) that occurred in the myeloma eells. thus suggesting that the abnormality responsible for tissue deposition is at the LC level [10]. In the other patients, the pla.sma cells synthesized normal-size LC that were secreted as monomers and dimers.…”

Section: Discussionmentioning

confidence: 97%

Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease

Khamlichi¹,

Aucouturier²,

Silvain³

et al. 1992

Clinical and Experimental Immunology

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SUMMARYPrevious data suggest thai structural abnormalities of imniunoglobulin light chains may be responsible lor non-amyloid light chain deposition disease (LCDD). We report on the complete primary sequence deduced from complementary (c)DNA analysis of a normal-sized K chain in ;t case of myeloma-associated LCDD. The patient's urine contained a K type Benec-Jones protein made of monomers and dimers of an unglycosylated K chain. The bone marrow myeloma cells contained intraccllular K and y chains by immunoHuorescence. Biosynthesis experiments showed the production of normal-sized v chains and ofK chains with the same apparent molecular mass (Mr) in SOS gels as the urinary K chain (2()00(» 270<)0). These K chains were secreted as assembled IgG molecules and as a large excess of free monomers and dimers. The complete sequence of two identical eDNA clones derived from a normal-sized K messenger RNA mdicated that this K chain belonged to the rare V.I V subgroup. The h. mRN A had an overall normal structure made up ofthe V,IV sequence rearranged to J, I and followed by a nonna! constant exon ofthe Ktn(.i) allotype. The variable region differed from the VJV-JJ germlinc sequence b> 17 amino acid substitutions. The peculiar sequence of the variable region of this K chain of a rare subgroup might relate lo its tissue deposition.

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Section: Discussionmentioning

confidence: 97%

Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease

Khamlichi¹,

Aucouturier²,

Silvain³

et al. 1992

Clinical and Experimental Immunology

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“…Most of the AL proteins we have studied contain carbohydrate [9], but we have been unable to establish if the glycosylation has anything to do with the fibrillogenic nature of AL chains. Glycosylation may play a direct role in tissue precipitation due to the binding to collagen and decreased catabolism of light chains [25].…”

Section: Discussionmentioning

confidence: 99%

The Amino Acid Sequence of the Glycosylated Amyloid Immunoglobulin Light Chain Protein AL MS

et al. 1997

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The authors report on the amino acid sequence of the glycosylated amyloid protein AL MS. The amyloid fibrils were extracted from the spleen of a patient (MS.) with amyloidosis. The protein AL MS was purified from the amyloid fibrils by gel filtration. SDS-PAGE performed on the purified protein material showed glycosylated protein bands in the range of 22 to 32 kDa, corresponding to polymerization of N-terminal fragments. The protein was characterized by amino acid analysis and Edman degradation. Tryptic digest combined with Staphylococcal V8 protease, chymotrypsin and pyroglutamate aminopeptidase digestion, as well as cleavage with BNPS-skatole, established the complete amino acid sequence of 168 residues. The protein was compared to other proteins in the SWISSPROT databank, showing homology with the immunoglobulin light chain variable subgroup lI. AL MS showed some unique amino acid substitutions. Highly conserved residues Gly(57) and Arg(61), were exchanged to arginine and glutamine, respectively, possibly altering the three-dimensional structure of the protein.

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“…43 It has been reported that somatic mutation of the V -IV family gene, which was deposited in the kidney, resulted in a potential N-glycosylation site. 44 However, one patient (UPN-AK4), whose V gene had such a potentially Nglycosylated site, did not have renal dysfunction. Thus, we could not find a clear correlation between the primary sequence of IgL and nephropathy.…”

Section: Comparison Of the Clinical Features And Igl Sequencesmentioning

confidence: 98%

“…In the light chain deposition disease which reportedly causes renal dysfunction, it has been suggested that an unusual sequence and/or glycosylation of the -chain is related to the pathogenesis. 43,44 However, in the patients with renal dysfunction, no common structure of IgL was observed. A potential N-glycosylation site, Asn-Phe-Thr at codon 70, 44 was found in only one patient AK4 (Figure 1), whose renal function was normal.…”

Section: Relationship Between Clinical Features and The Igl Sequencesmentioning

confidence: 99%

“…43,44 However, in the patients with renal dysfunction, no common structure of IgL was observed. A potential N-glycosylation site, Asn-Phe-Thr at codon 70, 44 was found in only one patient AK4 (Figure 1), whose renal function was normal. Furthermore, the V germline A27 gene was used in two patients (AK5 and GK2), but only the former had renal dysfunction.…”

Section: Relationship Between Clinical Features and The Igl Sequencesmentioning

confidence: 99%

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Characterization of the immunoglobulin light chain variable region gene expressed in multiple myeloma

et al. 1998

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We studied the organization, diversification and clinical significance of the immunoglobulin light chain (IgL) variable region genes expressed in 17 -chain and 16 -chain producing multiple myeloma (MM) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline V / genes, whereas one V and one V gene had only 75.5% and 65.9% homology, respectively. While all five J segments were equally used, only J -1 or J -2/3 was used among seven J segments. N nucleotide addition was found at two V -J and five V -J junctions. The -chain complementarity determining region (CDR)-3 was longer and more variable than the -chain CDR-3 mainly due to junctional flexibility of V and J segments. Somatic mutations were more frequent in the J than the J segments, and were distributed in the CDR-3 as well as the frame work region (FWR)-4. Those of the J segments, however, were limited to FWR-4. In FWR-4, replacement mutations were clustered at codon 106 of -chain and 103 of -chain. Thus nucleotide mutation or conservation was dependent on position, indicating a structural necessity of IgL for the development of myeloma cells in addition to a non-random distribution of mutations. There was no characteristic IgL sequence according to the isotype of M-protein, clinical stage or renal complication.

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Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease.

Cited by 84 publications

References 38 publications

Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease

Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease

The Amino Acid Sequence of the Glycosylated Amyloid Immunoglobulin Light Chain Protein AL MS

Characterization of the immunoglobulin light chain variable region gene expressed in multiple myeloma

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