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IgA is the predominant isotype of anti-?2 glycoprotein I antibodies in rheumatoid arthritis.

ABSTRACT: BACKGROUND:The aim of this study was to determine the frequency of anti-cardiolipin antibodies (aCL) and anti-?2 glycoprotein I antibodies (a?2GPI) among Tunisian patients with rheumatoid arthritis (RA). METHODS:Ninety RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 90 healthy blood donors (HBD) were studied. aCL and a?2GPI of isotype IgG, IgA and IgM were detected by ELISA. RESULT:The frequency of antiphopholipid antibodies (aPL) (aCL and/or a?2GPI) was significantly higher in patients with RA than in HBD (35.5% vs 11.1%, P = .0001). The frequencies of aCL and a?2GPI were significantly higher in patients than in healthy subjects (15.5% vs 5.5%, P = .04 and 32.2% vs 11.1%, P = .0005 respectively). a?2GPI-IgA were significantly more frequent in patients than in the control group (26.7% vs 7.8%, P = .0007). In patients, a?2GPI-IgA were significantly more frequent than a?2GPI-IgG (26.7% vs. 6.7%, P = .0003) and a?2GPI-IgM (26.7% vs 5.6%, P = .0001). In RA patients, the frequency of a?2GPI was significantly higher than that of aCL (32.2% vs 15.5%, P = .008). a?2GPI-IgA was significantly more frequent than aCL-IgA (26.7% vs 4.4%, P = .00005). The average titer of anti-CCP in aPL positive patients was significantly higher than in aPL negative patients (170.6 ± 50 RU/mL vs 147.7 ± 51 RU/mL, P = .04). Significant correlation was found between a?2GPI-IgA and anti-CCP (r = .235, P = .026). CONCLUSIONS:aPL and particularly a?2GPI-IgA are frequent in RA and are correlated with anti-CCP.

SUBMITTER: Melayah S

PROVIDER: S-EPMC7307372 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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IgA is the predominant isotype of anti-β2 glycoprotein I antibodies in rheumatoid arthritis.

Melayah Sarra S Changuel Maha M Mankaï Amani A Ghedira Ibtissem I

Journal of clinical laboratory analysis 20200122 6

<h4>Background</h4>The aim of this study was to determine the frequency of anti-cardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) among Tunisian patients with rheumatoid arthritis (RA).<h4>Methods</h4>Ninety RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 90 healthy blood donors (HBD) were studied. aCL and aβ2GPI of isotype IgG, IgA and IgM were detected by ELISA.<h4>Result</h4>The frequency of antiphopholipid antibodies (aPL) (aCL and/or a ...[more]

PMID: 31967351

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Project description:Background: Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with presence of anti-phospholipid antibodies (aPL). The APS classification criteria only consider the aPL of IgG/IgM isotype, however testing of aPL of IgA isotype is recommended when APS is suspected and consensus aPL are negative. IgA anti-βeta-2 glycoprotein-I (B2GP1) has been clearly related with occurrence of thrombotic events. Antibodies anti-B2GP1 of IgG/M isotypes recognize an epitope in Domain 1 (R39-G43), the epitopes that recognize IgA anti-B2GP1 antibodies are not well-identified. Aim: To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1. Methods: IgA antibodies to Domain-1(D1) and Domain-4/5(D4/5) of B2GP1 (ELISA) and epitope mapping on oligopeptide arrays of B2GP1 were evaluated in sera from a group of 93 patients with at least one thrombotic and with isolated positivity for IgA anti-B2GP1 antibodies (negative for other aPL). Results: A total of 47 patients (50.5%) were positive for anti-D4/5 and 23(25%) were positive for anti-D1. When peptide arrays were analyzed, three zones of B2GP1 reactivity were identified for more than 50% of patients. The center of these zones corresponds to amino acids 140(D3), 204(D4), and 264(D5). The peptides recognized on D3 and D4 contain amino acid sequences sharing high homology with proteins of microorganism that were previously related with a possible APS infectious etiology. In the three-dimensional structure of B2GP1, the three peptides, as the R39-G43 epitope, are located on the right side of the molecule (L-shape). The left side (J-shape) does not bind the antibodies. Conclusions: Patients with thrombotic APS clinical-criteria, and isolated IgA anti-B2GP1 positivity appear to preferentially bind, not to the D1 or D4/5 domains of B2GP1, but rather to three sites in D3, D4, and D5. The sites on D3 and D4 were previously described as the target identified by human monoclonal antibodies derived from patients that were capable of inducing APS in animal models. The localization of these epitopes opens a new route to explore to increase understanding of the patholophysiology of the APS and to propose new alternatives and therapeutic targets.

Dataset Information

IgA is the predominant isotype of anti-?2 glycoprotein I antibodies in rheumatoid arthritis.

Publications

IgA is the predominant isotype of anti-β2 glycoprotein I antibodies in rheumatoid arthritis.

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