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      Prevalence and Clinical Associations of Antiphospholipid Antibodies in Systemic Sclerosis: New Data From a French Cross-Sectional Study, Systematic Review, and Meta-Analysis

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          Abstract

          Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc.

          Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2glycoprotein I (anti-β2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies.

          Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8–10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18–33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31–22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 14% (9–20) with a high degree of heterogeneity among studies.

          Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8–10.4) and an overall worldwide pooled prevalence of 14% (9–20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc.

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          Most cited references40

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          QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

          In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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            Systemic sclerosis.

            Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy. Although systemic sclerosis is uncommon, it has a high morbidity and mortality. Improved understanding of systemic sclerosis has allowed better management of the disease, including improved classification and more systematic assessment and follow-up. Additionally, treatments for specific complications have emerged and a growing evidence base supports the use of immune suppression for the treatment of skin and lung fibrosis. Some manifestations of the disease, such as scleroderma renal crisis, pulmonary arterial hypertension, digital ulceration, and gastro-oesophageal reflux, are now treatable. However, the burden of non-lethal complications associated with systemic sclerosis is substantial and is likely to become more of a challenge. Here, we review the clinical features of systemic sclerosis and describe the best practice approaches for its management. Furthermore, we identify future areas for development.
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              Criteria for the classification of early systemic sclerosis.

              We propose criteria for the early diagnosis and classification of systemic sclerosis that reflect the vascular and serological advances of the last 2 decades.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                02 November 2018
                2018
                : 9
                : 2457
                Affiliations
                [1] 1Univ. Lille, U995, Lille Inflammation Research International Center , Lille, France
                [2] 2Inserm , Lille, France
                [3] 3CHU Lille, Département de Médecine Interne et Immunologie Clinique , Lille, France
                [4] 4Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique) , Lille, France
                [5] 5Inserm UMR1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Université de Lille, Centre Hosp. Univ. Lille, Institut Pasteur de Lille , Lille, France
                [6] 6CHU Lille, Institut d'Immunologie , Lille, France
                Author notes

                Edited by: Philippe Guilpain, Université de Montpellier, France

                Reviewed by: Amelie Servettaz, Centre Hospitalier Universitaire de Reims, France; Yves-Marie PERS, INSERM U1183 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice Et Immunothérapies, France

                *Correspondence: Vincent Sobanski vincent.sobanski@ 123456univ-lille.fr

                This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2018.02457
                6234954
                30464761
                a4e82388-fa57-4fa8-b346-d5d9e0f4c437
                Copyright © 2018 Sobanski, Lemaire-Olivier, Giovannelli, Dauchet, Simon, Lopez, Yelnik, Lambert, Hatron, Hachulla, Dubucquoi and Launay.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2018
                : 04 October 2018
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 46, Pages: 11, Words: 8033
                Categories
                Immunology
                Original Research

                Immunology
                systemic sclerosis,antiphospholipid antibodies,pulmonary hypertension,venous thrombosis,miscarriage

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