Anti-Ro/SSA and rheumatoid factor antibodies are associated with more severe lung involvement in patients with systemic sclerosis: a study from the EUSTAR database

Blaž Burja; Marouane Boubaya; Cosimo Bruni; Lisa Christ; Lidia P Ananyeva; Fabiola Atzeni; Christina Bergmann; Patricia E Carreira; Jeska De Vries-Bouwstra; Nicoletta Del Papa; Antonella Marcoccia; Okada Masado; Gabriela Riemekasten; Edoardo Rosato; Tim Schmeiser; Marco Sprecher; Anna-Maria Hoffmann-Vold; Florian Kollert; Sabina Guler; Oliver Distler; Muriel Elhai; EUSTAR collaborators

doi:10.1016/j.ejim.2026.106898

Anti-Ro/SSA and rheumatoid factor antibodies are associated with more severe lung involvement in patients with systemic sclerosis: a study from the EUSTAR database

Eur J Intern Med. 2026 May 26:106898. doi: 10.1016/j.ejim.2026.106898. Online ahead of print.

Authors

Blaž Burja¹, Marouane Boubaya², Cosimo Bruni¹, Lisa Christ³, Lidia P Ananyeva⁴, Fabiola Atzeni⁵, Christina Bergmann⁶, Patricia E Carreira⁷, Jeska De Vries-Bouwstra⁸, Nicoletta Del Papa⁹, Antonella Marcoccia¹⁰, Okada Masado¹¹, Gabriela Riemekasten¹², Edoardo Rosato¹³, Tim Schmeiser¹⁴, Marco Sprecher¹, Anna-Maria Hoffmann-Vold¹⁵, Florian Kollert¹⁶, Sabina Guler¹⁷, Oliver Distler¹, Muriel Elhai¹⁸; EUSTAR collaborators

Affiliations

¹ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Department of Clinical Research, CHU Avicenne, APHP, Bobigny, France.
³ Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ V.A. Nasonova Research Institute of Rheumatology Russian Federation, Moscow, Russia.
⁵ Rheumatology Unit, University of Messina, Italy.
⁶ Department Internal Medicine, University Hospital Erlangen, Germany.
⁷ Rheumatology Department, Hospital Universitario 12 De Octubre, Madrid, Spain.
⁸ Department Of Rheumatology, Leiden University Medical Center, Netherlands.
⁹ Scleroderma Clinic, UOC Reumatologia Clinica, ASST G. Pini-CTO, Milano, Italy.
¹⁰ Centro Di Riferimento Interdisciplinare Per La Sclerosi Sistemica, Rome, Italy.
¹¹ StLuke's International Hospital Immuno-Rheumatology Center, Tokyo, Japan.
¹² Department of Rheumatology and Clinical Immunology, University Clinic Schleswig-Holstein, Lübeck, Germany.
¹³ Sapienza University Of Rome-Department of Translational And Precision Medicine, Rome, Italy.
¹⁴ Krankenhaus St. Josef, Wuppertal-Elberfeld, Germany.
¹⁵ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
¹⁶ Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Rheumatology, University Hospital Basel, Basel, Switzerland.
¹⁷ Department of Pulmonary Medicine, Inselspital Bern University Hospital, University of Bern, Switzerland.
¹⁸ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: Muriel.elhai@usz.ch.

PMID: 42191555
DOI: 10.1016/j.ejim.2026.106898

Abstract

Background: As precision medicine is needed in systemic sclerosis (SSc) and SSc-associated interstitial lung disease (ILD), SSc non-specific antibodies might improve the risk stratification in this population.

Research question: To evaluate the prevalence and characterize the disease phenotype of SSc patients positive for anti-Ro/SSA alone or in combination with RF antibodies in the largest cohort of SSc patients, focusing on lung involvement.

Methods: Patients from the EUSTAR database with available data on anti-Ro/SSA and RF antibodies were included. Clinical characteristics of patients with or without anti-Ro/SSA and RF antibodies were compared at baseline. Multivariable logistic regression models were built to identify factors associated with ILD. In patients with ILD at baseline, multivariable mixed-effects models for longitudinal FVC and DLCO were built to assess the impact of anti-Ro/SSA and RF. Prognostic factors for the ILD progression and death during follow-up were tested by multivariable Cox proportional hazards regression.

Results: Among the 4,221 patients fulfilling the inclusion criteria, 641 (15.2%) had anti-Ro/SSA antibodies. These patients exhibited a higher prevalence of muscular involvement (p < 0.01), pulmonary hypertension (p = 0.06), and ILD (p < 0.01) at baseline. Over 14,066 follow-up visits, anti-Ro/SSA independently predicted the presence of ILD (OR 1.24 [1.07-1.43], p < 0.01). Among anti-Ro/SSA+/RF+ patients, who represented 4.1% of the cohort, ILD was more prevalent as compared to single positive or negative anti-Ro/SSA and RF patients. Anti-Ro/SSA+/RF+ double-positive patients had a more severe ILD, with lower FVC% (R -4.12 [-7.85;-0.40]; p = 0.03) and lower DLCO% (R -5.4[-9.05;-1.74]; p < 0.01).

Interpretation: In the large EUSTAR cohort, anti-Ro/SSA antibodies are detected in 15% of SSc patients and represent an independent risk factor for the presence and severity of ILD, particularly for cases with anti-Ro/SSA+/RF+ double positivity. These data support the inclusion of anti-Ro/SSA and RF antibodies in routine clinical practice to improve the risk stratification of SSc patients.

Keywords: Anti-Ro/SSA; Biomarkers; ILD; RF; SSc.