An Immunoglobulin Light Chain of Subgroup III1 of λ Type with a Free Sulfhydryl Group

1971 ◽  
Vol 49 (8) ◽  
pp. 900-902 ◽  
Author(s):  
Barbara M. Buchwald
Keyword(s):  
Light Chain ◽  
Sulfhydryl Group ◽  
Variable Region ◽  
Cysteine Residue ◽  
Immunoglobulin Light Chain ◽  
Myeloma Protein ◽  
Free Sulfhydryl Group ◽  
Bence Jones Proteins

A myeloma protein, Du, (γ1)2 (λ)2, is shown to have an extra cysteine residue in the light chain. This light chain is from the same λ variable region subgroup as are two Bence-Jones proteins, X and Bau, which also have an extra cysteine residue. The position of this residue is the same in all three chains.

Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain–associated amyloidosis (AL)

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3801-3807 ◽  
Author(s):  
Roshini S. Abraham ◽  
Susan M. Geyer ◽  
Tammy L. Price-Troska ◽  
Cristine Allmer ◽  
Robert A. Kyle ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Light Chain ◽  
Amyloid Fibrils ◽  
Clinical Presentation ◽  
Germ Line ◽  
Renal Involvement ◽  
Variable Region ◽  
Plasma Cell Dyscrasia ◽  
Gene Repertoire ◽  
Immunoglobulin Light Chain

AbstractLight chain–associated amyloidosis (AL) is a plasma cell dyscrasia in which the secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There is considerable heterogeneity in clinical presentation, and prognosis of the disease relates to the severity of organ dysfunction induced by amyloid deposits. The mechanisms by which the amyloid fibrils are deposited as well as the predilection for specific organ sites have not been clearly elucidated. This study characterizes the repertoire of immunoglobulin light chain variable genes used by the clonal B cell in AL amyloid patients, and the association of light chain variable region (VL) genes with clinical presentation and outcome is assessed in 58 (32 λ and 26 κ) patients. A preferential use of VL germ-line genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germ-line donor, 6a, and renal involvement as well as the Vλ III gene, 3r, with soft-tissue AL. The use of a biased VL gene repertoire also correlated with clinical outcome, revealing important trends for predicting prognosis. The use of Vλ II germ-line genes was associated with cardiac amyloidosis and affected survival adversely. The presence of multiple myeloma also correlated with a poor prognosis. The presence of renal disease, on the other hand, was associated with improved survival. Therefore, identification of the clonal VL gene in AL has important implications in determining clinical outcome.

Immunoglobulin Light Chain Gene Constant Region Is An Invariable Part of Amyloid Deposits in AL Amyloidosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3128-3128
Author(s):  
Jason D. Theis ◽  
Julie A. Vrana ◽  
Jeffrey D. Gamez ◽  
Angela Dispenzieri ◽  
Stephen R. Zeldenrust ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Light Chain ◽  
Proteomic Analysis ◽  
Laser Microdissection ◽  
Variable Region ◽  
Al Amyloidosis ◽  
Constant Region ◽  
Immunoglobulin Light Chain ◽  
Amyloid Deposits ◽  
Region I

Abstract Background: Amyloidosis caused by immunoglobulin light chain (IGLC) deposition, so-called AL-type or primary amyloidosis, is the most common type of amyloidosis. It has been long believed that IGLC variable regions form the core of the AL-type amyloid deposits and peptides derived from IGLC constant region peptides are only occasionally integrated into this core. For this reason, the scientific effort to identify thge risk factors for development of AL amyloidosis and the biochemical characteristics amyloid deposits has focused on IGLC variable region derived proteins. To understand the peptide constituents of AL amyloidosis better, we undertook a comprehensive study of AL amyloidosis using a novel mass spectrometry based proteomic analysis approach. Methods: Paraffin embedded tissue from 100 cases of AL amyloidosis was studied. In each case amyloid type was previously established by clinical and pathological examination. Congo red stained paraffin sections were prepared and amyloid deposits were microdissected by laser microdissection microscopy. The microdissected tissue fragments were processed and trypsin digested into peptides. The peptides were analyzed by nano-flow liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS). The resulting LC-MS/MS data were correlated to theoretical fragmentation patterns of tryptic peptide sequences from the Swissprot database using Scaffold (Mascot, Sequest, and X!Tandem search algorithms). Peptide identifications were accepted if they could be established at greater than 90.0% probability and protein identifications were accepted if they could be established at greater than 90.0% probability and contain at least 2 identified spectra. The identified proteins were subsequently examined for the presence or absence of amyloid related peptides. Results and Discussion: LC-MS/MS gave peptide profiles consistent with AL amyloidosis in each case. The analysis showed IGLC-lambda deposition in 66 cases and IGLC-kappa deposition in 34 of cases. In each case, LC MS/MS confirmed the previous clinicopathological diagnosis. Interestingly peptides representing IGLC constant region were present in each case. Using this LC-MS/MS methodology, theoretically it is possible to cover 78% of the IGLC-lambda and 87% IGLC-kappa constant regions. In our samples, the average coverage of the IGLC-lambda and IGLC-kappa constant regions were 40% (range 14–78%)and 55% (range 16–87%) respectively. Additionally, the distribution of the peptides suggested that in the majority of the cases whole of the IGLC constant region was deposited. LC MS/MS also identified IGLC-lambda variable region peptides in 37 of 66 cases and IGLC-kappa variable region peptides in 29 of 34 cases studied. The variable region coverage was more restricted and the peptides identified were frequently within the framework segments. It is likely that the peptides derived from CDR segments were present but not detected by the methodology as somatic hypermutation randomly alters the amino acid sequence in the CDR segments and such new sequences are not available in public databases used by algorithms for peptide identification. In the cases with the IGLC variable region hits, it was also possible to assign variable region family usage. IGLC-lambda cases frequently used IGLC-lambda variable region I, II and III families whereas, in IGLC-kappa cases, IGLC-kappa variable region I and III families dominated. Conclusions: AL amyloidosis can be accurately diagnosed using laser microdissection and LC-MS/MS based proteomic analysis in routine clinical specimens. AL amyloidosis invariably contains IGLC constant region peptides and, frequently, the whole of the constant region is deposited. This finding suggests that studies on molecular pathogenesis of amyloidosis should not only consider the IGLC-variable region but also the constant region. It is possible to identify IGLC variable region family usage in AL amyloidosis using LC MS/MS based proteomic analysis. In the clinical setting, this information may be helpful in predicting organ distribution and clinical outcome.

scholarly journals A new isotype sequence (V κ 27) of the variable region of κ-light chains from a mouse hybridoma-derived anti-(streptococcal group A polysaccharide) antibody containing an additional cysteine residue. Application of the dimethylaminoazobenzene isothiocyanate technique for the isolation of peptides

1983 ◽  
Vol 211 (1) ◽  
pp. 173-180 ◽  
Author(s):  
J Y Chang ◽  
H Herbst ◽  
R Aebersold ◽  
D G Braun
Keyword(s):  
Light Chain ◽  
Variable Region ◽  
Complete Sequence ◽  
Cysteine Residue ◽  
Kappa Light Chain ◽  
Column Formation ◽  
Peptide Derivatives ◽  
Group A ◽  
Polysaccharide Antibody

The first complete sequence of the variable region of a kappa-light chain (V kappa) from a mouse anti-(streptococcal group A polysaccharide) antibody (immunoglobulin 7S34.1) is reported. Immunoglobulin 7S34.1 was isolated from the ascitic fluid of hybridoma 7S34.1 previously cloned in vitro. A newly developed technique for the isolation of peptides by using pre-column formation of peptide derivatives with dimethylaminoazobenzene isothiocyanate also served to complete the sequence. The sequence of the variable region of the kappa-light chain of immunoglobulin 7S34.1 defines a new mouse V kappa isotype (V kappa 27) and is the first mouse immunoglobulin light-chain variable region to be shown to have an extra cysteine residue at position 48.

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