Contribution of anti-β2glycoprotein I IgA antibodies to the diagnosis of anti-phospholipid syndrome: potential interest of target domains to discriminate thrombotic and non-thrombotic patients

Despierres, Laura; Beziane, Abdou; Kaplanski, Gilles; Granel, B.; Serratrice, Jacques; Cohen, William; Bretelle, Florence; Rossi, P.; Morange, Pierre‐Emmanuel; Weiller, Pierre Jean; Harlé, J.-R.; Bongrand, Pierre; Bardin, Nathalie

doi:10.1093/rheumatology/keu003

Cited by 31 publications

(30 citation statements)

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“…[37, 38] Our work also contributes to solving the third problem: defining the significance of isolated positivity of IgA with aB2GPI in asymptomatic population.…”

Section: Discussionmentioning

confidence: 99%

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

et al. 2017

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BackgroundThe antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined.ObjectiveTo test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up.Methods244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL.ResultsDuring the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p<0.001).The incidence rate of APS-events was 3.1% per year in IgA-aB2GP1 positive patients and 0.6% per year in the control group. Arterial thrombosis were the most frequent APS-events (N = 25, 55%) and were mainly observed in Group-1 patients (21 vs 4, p = 0.001). Multivariate analysis were shown as independent risk-factors for the development of APS-events, age, sex (men) and presence of IgA-aB2GP1 (odds ratio 5.25, 95% CI 2.24 to 12.32).ConclusionThe presence of IgA-aB2GP1 in people with no history of APS-events is the main independent risk factor for the development of these types of events, mainly arterial thrombosis.

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“…[37, 38] Our work also contributes to solving the third problem: defining the significance of isolated positivity of IgA with aB2GPI in asymptomatic population.…”

Section: Discussionmentioning

confidence: 99%

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

et al. 2017

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“…IgA antibodies are certainly important in various autoimmune diseases. Patients with only IgA anti-phospholipid antibodies have been shown to have the same clinical manifestations as patients with IgG or IgM anti-phospholipid antibodies [15, 16]. It is possible, however, that IgA autoantibodies may play a different role in disease pathogenesis in SS than IgM or IgG antibodies.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Autoantibodies in Patients with Primary and Secondary Sjogren’s Syndrome

Langhe¹,

Bossuyt²,

Shen³

et al. 2017

TORJ

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Background: Antibodies to salivary gland protein 1 (SP1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP) were discovered in an animal model of Sjogren’s syndrome (SS). Their expression was noted in patients with SS, especially those with lower focus scores on lip biopsies and those with early disease lacking antibodies to Ro and La.Objective: The current studies evaluated these autoantibodies in patients with long-standing SS expressing high levels of anti-Ro antibodies and in patients with Sjogren’s syndrome secondary to systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue disease (MCTD).Method: Sera were obtained from patients and evaluated by ELISA for IgG, IgA and IgM antibodies to SP1, CA6 and PSP.Results: IgA anti-CA6 antibodies were noted in 38% of these patients, but anti-SP1, CA6 and PSP IgM or IgG antibodies were identified only in a minority of patients. In patients with secondary SS, antibodies to SP1/CA6/PSP were more sensitive and specific than anti-Ro .Conclusion: While more studies are needed, antibodies to SP1, CA6 and PSP provide valuable markers for the diagnosis of primary and secondary SS, especially early in the course of the disease.

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“…Additionally, although IgA antibodies so far have not been included in the current classification criteria, measurement of (isolated) IgA anti-β 2 GPI antibodies, often a subclass of IgA antibodies targeting domain IV/V, previously showed to identify additional patients with clinical features of APS. 48,59,65,[77][78][79] The pathogenicity of purified IgA antiβ 2 GPI antibodies, reactive against domains I and IV/V, was demonstrated in a mouse model of thrombosis. 77 As positivity for IgA antibodies has been shown to largely overlap with other aPLs, it may be advisable to only measure IgA (particularly anti-β 2 GPI) in patients negative for IgG/IgM but in whom APS is suspected.…”

Section: Evidence For Other Noncriteria Antibodiesmentioning

confidence: 99%

The Significance of Antibodies against Domain I of Beta-2 Glycoprotein I in Antiphospholipid Syndrome

Kelchtermans

Chayouâ

Laat

2017

Semin Thromb Hemost

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The antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Progress is being made in understanding the pathogenesis of the syndrome, but difficulties persist in the identification of patients at risk for thrombosis and/or pregnancy morbidity. Beta-2 glycoprotein I (βGPI), a plasma protein consisting of five sushi domains, is thought to be the main antigenic target of aPLs. Antibodies recognizing domain I of βGPI are predominantly present in patients with an elevated risk of thrombosis, whereas antidomain IV/V antibodies are found in nonthrombotic autoimmune diseases. Indeed, domain I antibodies proved to be pathogenic in multiple studies. Retrospective studies have provided evidence for an added clinical value of antidomain I antibodies in the risk stratification of patients with APS. Still, wide ranges of odds ratio exist between studies, probably due to differences in the study and control population, and detection methods used. Despite the proven pathogenicity of antidomain I antibodies and their correlations with clinical manifestations of APS, heterogeneity of the current studies has prohibited their acceptance in the official diagnostic criteria. Well-designed large longitudinal prospective studies with available and new, preferentially functional, assays for the risk stratification of patients with APS are required.

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Contribution of anti-β2glycoprotein I IgA antibodies to the diagnosis of anti-phospholipid syndrome: potential interest of target domains to discriminate thrombotic and non-thrombotic patients

Abstract: Our study confirmed the interest of aβ2GP1 IgA in the exploration of APS and suggests that identification of target domains of aβ2GP1 IgA may be useful in the evaluation of thrombotic risk in SLE patients.

Cited by 31 publications

References 11 publications

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

Evaluation of Autoantibodies in Patients with Primary and Secondary Sjogren’s Syndrome

The Significance of Antibodies against Domain I of Beta-2 Glycoprotein I in Antiphospholipid Syndrome

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