The pathogenicity of antibodies against β2-glycoprotein I (anti-β2GPI) 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-β2GPI 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 β2GPI 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-β2GPI. Peptides D (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV) represent surface amino acid clusters on β2GPI. 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-β2GPI to different epitopes on β2GPI. Classification of IgG anti-β2GPI into subgroups regarding epitope specificity and avidity could represent an additional tool in understanding their pathogenicity in APS.

Immunoreactivity and avidity of IgG anti-β2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of β2-glycoprotein I / Artenjak, A; Locatelli, I; Brelih, H; Simonič, Dm; Ulcova Gallova, Z; Swadzba, J; Musial, J; Iwaniec, T; Stojanovich, L; Conti, Fabrizio; Valesini, Guido; Avčin, T; Cohen Tervaert, Jw; Shoenfeld, Y; Blank, M; Ambrožič, A; Sodin Semrl, S; Božič, B; Cučnik, S.. - In: IMMUNOLOGIC RESEARCH. - ISSN 0257-277X. - STAMPA. - 61:1-2(2015), pp. 35-44. [DOI 10.1007/s12026-014-8578-0]

Immunoreactivity and avidity of IgG anti-β2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of β2-glycoprotein I.

CONTI, FABRIZIO;VALESINI, Guido;
2015

Abstract

The pathogenicity of antibodies against β2-glycoprotein I (anti-β2GPI) 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-β2GPI 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 β2GPI 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-β2GPI. Peptides D (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV) represent surface amino acid clusters on β2GPI. 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-β2GPI to different epitopes on β2GPI. Classification of IgG anti-β2GPI into subgroups regarding epitope specificity and avidity could represent an additional tool in understanding their pathogenicity in APS.
2015
Antiphospholipid syndrome; Anti-b2GPI antibodies; b2GPI peptides; Anti-b2GPI-related peptides antibodies; Avidity
01 Pubblicazione su rivista::01a Articolo in rivista
Immunoreactivity and avidity of IgG anti-β2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of β2-glycoprotein I / Artenjak, A; Locatelli, I; Brelih, H; Simonič, Dm; Ulcova Gallova, Z; Swadzba, J; Musial, J; Iwaniec, T; Stojanovich, L; Conti, Fabrizio; Valesini, Guido; Avčin, T; Cohen Tervaert, Jw; Shoenfeld, Y; Blank, M; Ambrožič, A; Sodin Semrl, S; Božič, B; Cučnik, S.. - In: IMMUNOLOGIC RESEARCH. - ISSN 0257-277X. - STAMPA. - 61:1-2(2015), pp. 35-44. [DOI 10.1007/s12026-014-8578-0]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/625140
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