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Analysis of somatic hypermutation and antigenic selection in the clonal B cell in immunoglobulin light chain amyloidosis (AL).

Abstract：

:Light chain amyloidosis (AL) is a protein folding disorder with an underlying B cell neoplasia where the monoclonal immunoglobulin light chains (LCs) produced from insoluble amyloid fibrils. The deposition of these fibrillar aggregates in vital organs causes severe organ dysfunction over time and is associated with high mortality. We have identified the postgerminal center status of the B cell clone by evaluating the presence of somatic hypermutation in the variable region of the LC gene in 27 (13 of the lambda and 14 of the kappa subtype) AL patients. Seven of the 27 clones showed statistically significant evidence of antigenic selection, using a multinomial algorithm. The framework region mutations were selected for conservation of protein structure in 13 of the 27 patients. Additionally, mutational clusterspots were identified at specific positions in the nucleotide and deduced protein sequence that could potentially contribute to destabilizing interactions resulting in a propensity to form amyloid.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Abraham RS,Geyer SM,Ramírez-Alvarado M,Price-Troska TL,Gertz MA,Fonseca R

doi

10.1023/B:JOCI.0000029113.68758.9f

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

340-53

issue

4

eissn

0271-9142

issn

1573-2592

pii

487247

journal_volume

24

pub_type

杂志文章

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