Primary Sjögren's Syndrome: Impact of Quantitative Anti-Ro52 Antibody Analysis on Patient Prognosis and Stratification (Ro-SjS)

Official title

Primary Sjögren's Syndrome: Impact of Quantitative Anti-Ro52 Antibody Analysis on Patient Prognosis and Stratification

Overview

This study aims to evaluate the prognostic value of quantitative anti-Ro52 antibody levels in patients with primary Sjögren's Syndrome. Anti-Ro52 antibodies are frequently detected in this autoimmune disease, but their specific role in disease stratification, systemic involvement, and long-term outcomes remains unclear. Through a prospective cohort analysis, the investigators will investigate the association between anti-Ro52 titers and clinical phenotypes, including extraglandular manifestations, immunological profiles, and disease progression. The objective is to determine whether quantitative assessment of anti-Ro52 antibodies can serve as a biomarker to refine risk stratification and guide personalized management in primary Sjögren's Syndrome.

Detailed description

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, leading to dryness symptoms, and by a wide spectrum of systemic manifestations. Autoantibodies, particularly anti-Ro/SSA antibodies, are hallmark features of the disease and play a central role in diagnosis and classification. Among these, anti-Ro52 antibodies have been increasingly recognized as a distinct immunological marker, often co-occurring with or without anti-Ro60 and anti-La antibodies.

While qualitative detection of anti-Ro52 is widely used in routine clinical practice, the clinical significance of their quantitative levels remains underexplored. Recent studies suggest that high titers of anti-Ro52 may be associated with more severe systemic disease, including pulmonary, muscular, and neurological involvement, as well as with increased interferon signature activity. However, no consensus currently exists regarding their utility as a prognostic or stratification biomarker in pSS.

This retrospective cohort study aims to assess whether quantitative anti-Ro52 antibody levels correlate with specific clinical phenotypes, immunological patterns, and long-term outcomes in patients with primary Sjögren's Syndrome. Clinical data, including organ involvement, biological markers, disease activity scores (e.g., ESSDAI), and treatment response, will be collected and analyzed in relation to anti-Ro52 titers measured by standardized quantitative assays.

The objectives are:

* To determine whether high anti-Ro52 titers are predictive of systemic involvement at baseline or during follow-up; * To identify clusters of patients based on anti-Ro52 levels and associated clinical/immunological profiles; * To evaluate the potential of quantitative anti-Ro52 testing as a tool for risk stratification and personalized therapeutic strategies.

This study will provide insights into the prognostic implications of anti-Ro52 in pSS and contribute to refining clinical management and follow-up of affected patients.

Primary outcome measures

• Occurrence of a severe clinical event during follow-up [Time frame: 2 years]

Secondary outcome measures (4)

• Frequency of anti-Ro52 positiviy [Time frame: 2 years]
• Association between anti-Ro52 antibody levels and disease activity [Time frame: 2 years]
• Correlation between quantitative anti-Ro52 antibody levels and clinical/immunological features at baseline. [Time frame: 2 years]
• Classification of patients into subgroups (clusters) based on anti-Ro52 levels. [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years at the time of inclusion,
• Diagnosis of primary Sjögren's syndrome according to the 2016 ACR/EULAR classification criteria,
• Quantitative measurement of anti-Ro52 antibodies performed as part of routine care, starting from 2020 (date of routine implementation in the laboratory),
• Documented medical follow-up in the internal medicine department (or other participating department),
• No objection to participation in research after being informed according to current regulations (record of non-opposition if applicable).

Exclusion criteria

• Presence of another systemic autoimmune connective tissue disease, including systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, rheumatoid arthritis (except nonspecific arthralgia without classification criteria),
• History of solid organ or bone marrow transplantation,
• Severe immunosuppression unrelated to Sjögren's syndrome (e.g., HIV infection, ongoing chemotherapy for active hematologic malignancy),
• Incomplete or non-exploitable clinical or biological data preventing analysis of primary or secondary endpoints,
• Individuals under legal protection measures (e.g., guardianship).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• Université de Nancy — Vandœuvre-lès-Nancy

Publications

• Bettacchioli E, Saraux A, Tison A, Cornec D, Dueymes M, Foulquier N, Hillion S, Roguedas-Contios AM, Benyoussef AA, Alarcon-Riquelme ME, Pers JO, Devauchelle-Pensec V; PRECISESADS Clinical Consortium, and PRECISESADS Sjogren Consortium. Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjogren Disease Severity Through Interferon Pathway Activation. Arthritis Rheu PMID 38130019
• Decker P, Moulinet T, Pontille F, Cravat M, De Carvalho Bittencourt M, Jaussaud R. An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management. Autoimmun Rev. 2022 Mar;21(3):103013. doi: 10.1016/j.autrev.2021.103013. Epub 2021 Dec 9. PMID 34896652

Identifiers

NCT: NCT07414667 · 2025PI076

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗