Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.

Objectives: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.
Methods: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
Findings: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I ² : 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
Interpretation: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amelie Leurs reports a relationship with CSL Vifor that includes: travel reimbursement. Dr. Amelie Leurs reports a relationship with NOVARTIS that includes: board membership. Prof David Launay reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with Biocryst Pharmaceuticals, Inc. that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with CSL Behring LLC that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with GSK that includes: funding grants. Prof David Launay reports a relationship with Octapharma that includes: funding grants. Prof David Launay reports a relationship with Pfizer Inc. that includes: funding grants. Dr. Luc Dauchet reports a relationship with FEDER ECRIN that includes: funding grants. Dr. Luc Dauchet reports a relationship with ADEM French environment agency that includes: funding grants. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by Euroimmun. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by D-Tek. Prof Vincent Sobanski reports financial support was provided by Lille University Hospital. Prof Vincent Sobanski reports a relationship with Grifols Inc. that includes: consulting or advisory and funding grants. Prof Vincent Sobanski reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory. Prof Vincent Sobanski reports a relationship with Ultragenyx Pharmaceutical Inc. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)