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Publication Detail
Molecular and genetic characterizations of five pathogenic and two non- pathogenic monoclonal antiphospholipid antibodies
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Chukwuocha RU, Zhu M, Cho CS, Visvanathan S, Hwang KK, Rahman A, Chen PP
  • Publication date:
    10/2002
  • Pagination:
    299, 311
  • Journal:
    Molecular Immunology
  • Volume:
    39
  • Issue:
    5-6
  • Print ISSN:
    0161-5890
  • Keywords:
    ACCUMULATION, ACT, adolescent, adult, Amino Acid Sequence, anti-DNA, antibodies, Antibodies, Antiphospholipid, Antibodies, Monoclonal, Antibody, ANTIGEN, antiphospholipid, Antiphospholipid Syndrome, Arginine, As, ASSAY, autoimmune, Base Sequence, BINDING, Blood, Blood Clotting, CHAIN, chains, characterization, chemistry, Complementarity Determining Regions, disease, Female, fetal, GENE, Genes, genetic, genetics, heavy chain, Id, IgG, IM, IMMUNOGLOBULIN, Immunoglobulin Variable Region, IMMUNOGLOBULINS, Immunoglobulins, Heavy-Chain, in vitro, In-vitro, LA, loss, Male, May, MECHANISM, mechanisms, model, Molecular, Molecular Sequence Data, Molecular Structure, MOLECULAR-STRUCTURE, MOLECULAR-STRUCTURES, mouse, MOUSE MODEL, NUMBER, Patient, patients, production, RECURRENT, REGION, regions, Structure, Support, Non-U.S.Gov't, Support, U.S.Gov't, P.H.S., Syndrome, Thrombocytopenia, Thrombosis, Unknown, variable, VITRO
  • Notes:
    UI - 22209755 LA - eng RN - 0 (Antibodies, Antiphospholipid) RN - 0 (Antibodies, Monoclonal) RN - 0 (Complementarity Determining Regions) RN - 0 (Immunoglobulin Variable Region) RN - 0 (Immunoglobulins, Heavy-Chain) PT - Journal Article ID - 5 K14 HL03523/HL/NHLBI DA - 20020910 IS - 0161-5890 SB - IM CY - England
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies
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