Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Giles IP, Haley JD, Nagl S, Isenberg DA, Latchman DS, Rahman A
  • Publication date:
  • Pagination:
    246, 265
  • Journal:
    Seminars in Arthritis and Rheumatism
  • Volume:
  • Issue:
  • Print ISSN:
  • Keywords:
    ACCUMULATION, Amino Acid Sequence, analysis, antibodies, Antibodies, Antiphospholipid, Antibody, ANTIGEN, antiphospholipid, aPL, Arginine, As, Asparagine, beta, BINDING, chemistry, Complementarity Determining Regions, development, distribution, DRUG, DRUGS, families, family, GENE, genetics, glycoprotein, Glycoproteins, HYPOTHESIS, IDENTIFICATION, IgG, Igm, IM, IMMUNOGLOBULIN, immunology, interaction, LA, literature, lysine, M, May, Methods, Molecular Sequence Data, Mutation, MUTATIONS, Nucleotide, PATHOGENESIS, Phospholipids, PROBABILITY, PUBLISHED, REGION, regions, relevance, REPLACEMENT, Result, Review, SEQUENCE, SEQUENCES, Software, Support, Non-U.S.Gov't, Syndrome, Systematic, treatment, understanding, Use, variable
  • Notes:
    DA - 20030306 IS - 0049-0172 LA - eng PT - Journal Article PT - Review PT - Review Literature RN - 0 (Antibodies, Antiphospholipid) RN - 0 (Glycoproteins) RN - 0 (beta 2-glycoprotein I) SB - IM
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
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
ICH - Directors Office
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by