Immunoreactivity and avidity of IgG anti-beta 2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of beta 2-glycoprotein I

A. Artenjak, I. Locatelli, H. Brelih, D. M. Simonic, Z. Ulcova-Gallova, J. Swadzba, J. Musial, T. Iwaniec, L. Stojanovich, F. Conti, G. Valesini, T. Avcin, J. W. Cohen Tervaert, Y. Shoenfeld, M. Blank, A. Ambrozic, S. Sodin-Semrl, B. Bozic, S. Cucnik*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

The pathogenicity of antibodies against beta 2-glycoprotein I (anti-beta 2GPI) depends on multiple factors such as subclass type, epitope binding and avidity. Due to their large heterogeneity, their impact on antiphospholipid syndrome (APS) onset is still not fully clarified. We studied the binding characteristics of IgG anti-beta 2GPI with known avidity from sera of 201 autoimmune patients (87 with APS, 67 with APS associated with systemic lupus erythematosus (SLE), 47 with only SLE) to six beta 2GPI peptides corresponding to amino acid clusters on domains I-II, II, III and III-IV by indirect ELISA and evaluated their association with clinical features of APS. Peptides A (LKTPRV; domain I-II), B (KDKATF; domain IV) and C (TLRVYK; domain III) were derived from a hexapeptide phage display library previously shown to react with pathogenic monoclonal anti-beta 2GPI. Peptides D (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV) represent surface amino acid clusters on beta 2GPI. The percentage of patients positive for peptides were observed as follows: 30.3 % for peptide D, 28.90 % for B, 25.9 % for C, 24.9 % for E, 24.4 % for F and 10.0 % for A. The anti-peptide antibodies in studied serum samples were predominantly of heterogeneous avidity, followed by law avidity anti-peptide antibodies, whereas only a few were of high avidity. Positive and negative correlations were found between several anti-peptide antibodies and the rate of thrombosis. Our results indicated diverse reactivity of IgG anti-beta 2GPI to different epitopes on beta 2GPI. Classification of IgG anti-beta 2GPI into subgroups regarding epitope specificity and avidity could represent an additional tool in understanding their pathogenicity in APS.
Original languageEnglish
Pages (from-to)35-44
JournalImmunologic Research
Volume61
Issue number1-2
DOIs
Publication statusPublished - Feb 2015

Keywords

  • Antiphospholipid syndrome
  • Anti-beta 2GPI antibodies
  • beta 2GPI peptides
  • Anti-beta 2GPI-related peptides antibodies
  • Avidity

Cite this