当前位置： SCI文献检索 > SEMINARS IN ARTHRITIS AND RHEUMATISM期刊下所有文献 > A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs.

A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs.

Abstract：

OBJECTIVE:Previous studies have suggested the importance of somatic mutations and certain residues in the complementarity determining regions (CDRs) of antiphospholipid antibodies (aPL) implicated in the pathogenesis of antiphospholipid antibody syndrome (APS). The authors tested this hypothesis by carrying out a systematic analysis of all published aPL sequences. METHODS:Each aPL variable region sequence was aligned to the closest germline counterpart in the VBASE Sequence Directory by using DNAPLOT software, allowing analysis of nucleotide homology and distribution of somatic mutations. The probability that this distribution arose as a result of antigen-driven accumulation of replacement mutations in the CDRs was tested statistically. RESULTS:There was no preferential gene or family use in the 36 aPL sequences identified. Immunoglobulin (Ig) M aPL had few somatic mutations compared with IgG. Of the IgG aPL, 9 of 14 showed evidence of antigen-driven accumulation of replacement mutations in the CDRs. Multinomial analysis allowed a clearer statistical identification of sequences that had been subject to antigen drive. The more specific IgM aPL and some IgG aPL displayed an accumulation of arginine, asparagine, and lysine residues in CDRs. CONCLUSIONS:High-specificity binding in IgG aPL, but not in more specific IgM aPL, is conferred by antigen-driven somatic mutation. This may in part be caused by an accumulation of arginine, asparagine, and lysine residues in the CDRs, which are germlines encoded in the more specific IgM aPL, but often arise because of somatic mutation in IgG aPL. RELEVANCE:An understanding of the role of arginine, asparagine, and lysine residues in the binding of pathogenic aPL to phospholipids, and to beta(2)-glycoprotein I, may eventually help in the development of drugs to interfere with those interactions, and thereby improve the treatment of antiphospholipid antibody syndrome.

journal_name

Semin Arthritis Rheum

journal_title

Seminars in arthritis and rheumatism

authors

Giles IP,Haley JD,Nagl S,Isenberg DA,Latchman DS,Rahman A

doi

10.1053/sarh.2003.49994

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

246-65

issue

eissn

0049-0172

issn

1532-866X

pii

S0049017202701066

journal_volume

pub_type

杂志文章,评审

在线工具

A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs.