Anti-NOR-90 autoantibodies and clinical associations in systemic sclerosis: an international retrospective cohort study
Abstract Background Autoantibodies against NOR-90 are rare and have been associated with systemic sclerosis (SSc). This study seeks to identify the characteristics of SSc participants with anti-NOR-90 autoantibodies. Methods An international (Canada, Australia, USA, Mexico) cohort of 2143 SSc participants was included. Sera were tested using a line immunoassay (Euroimmun, Lübeck, Germany). Clinical associations with anti-NOR-90 autoantibodies were investigated. Single-specificity anti-NOR-90-positive was defined as anti-NOR-90-positivity without other SSc-related autoantibodies, except for anti-Ro52/TRIM21. Results 115 (5%) participants were anti-NOR-90-positive, of whom the majority overlapped with other autoantibodies. Anti-NOR-90 positivity overall was associated with a higher frequency of calcinosis (35% vs. 24%, OR 1.70, 95% CI: 1.13, 2.52), digital ulcers (62% vs. 49%, OR 1.70, 95% CI: 1.12, 2.61) and arthritis (37% vs. 29%, OR 1.61, 95% CI: 1.06, 2.40). Single-specificity anti-NOR-90-positive participants ( n = 21) a significantly lower mean % predicted forced vital capacity (FVC, 82.0% vs. 91.3%) and diffusing capacity (DLCO, 58.9% vs. 69.0%), and a trend toward higher prevalence of interstitial lung disease (61% vs. 40%, OR 2.36, 95% CI: 0.92, 6.45) and lower median mRSS (4.0 vs. 7.0). Anti-NOR-90 autoantibodies were not associated with increased cancer (10% vs. 8%) or mortality (adjusted HR 1.28, 95% CI: 0.92, 1.79, log rank p = 0.3). Results from sensitivity analyses excluding anti-Ro52/TRIM21 from single-specificity definition were consistent in direction and magnitude. Conclusion In this large multicentre cohort, anti-NOR-90 autoantibodies commonly overlapped with other SSc-autoantibodies. Single-specificity anti-NOR-90 positivity was associated with more frequent interstitial lung disease and a tendency for lower mRSS.
Authors
- Geneviève Gyger
- Valérie Leclair (ORCID: https://orcid.org/0000-0001-8643-6697)
- Marvin J. Fritzler (ORCID: https://orcid.org/0000-0003-1652-6608)
- Mandana Nikpour (ORCID: https://orcid.org/0000-0002-6585-5611)
- Nancy Maltez (ORCID: https://orcid.org/0000-0002-8535-4312)
- Nava Ferdowsi (ORCID: https://orcid.org/0000-0002-8852-7776)
- Mianbo Wang (ORCID: https://orcid.org/0009-0007-7148-2827)
- Alannah Quinlivan (ORCID: https://orcid.org/0000-0002-7750-507X)
- Maryam Tabesh (ORCID: https://orcid.org/0000-0002-3769-9666)
- S. Hoa
- Diane Apostolopoulos (ORCID: https://orcid.org/0000-0003-1078-6732)
- Hao Cheng Shen (ORCID: https://orcid.org/0009-0002-2452-3511)
- Maggie Larché (ORCID: https://orcid.org/0000-0002-9506-1249)
- Paul R. Fortin (ORCID: https://orcid.org/0000-0002-7278-2596)
- Jenny Walker (ORCID: https://orcid.org/0000-0002-8863-0458)
- Gloria A. Salazar (ORCID: https://orcid.org/0000-0003-4286-2250)
- Alena Ikic
- Yves Troyanov
- Marie Hudson (ORCID: https://orcid.org/0000-0001-6718-2468)
- May Y. Choi
- Janet Pope
- Tatiana S. Rodríguez-Reyna
- N Khalidi
- Susanna Proudman
- Carter Thorne
- Gabor Major
- Genetics versus Environment in Scleroderma Outcome Study
- Evelyn Sutton
- Dylan Hansen
- Murray Baron
- Laureen V. Host
- Gene-Siew Ngian
- Australian Scleroderma Interest Group (ASIG)
- Maureen D. Mayes
- Peter Docherty
- Laura Ross
- May Y. Choy
- Joanne Sahhar
- Wendy Stevens
- Sharon LeClercq
- Ariel Masetto
- Niall Jones
- Terry A. McNearney
- David Robinson
- Shervin Assassi
- Mohamed Osman
Institutions
- Western University (CA)
- Royal Adelaide Hospital (AU)
- University of Alberta (CA)
- The University of Melbourne (AU)
- University of Calgary (CA)
- Royal Prince Alfred Hospital (AU)
- Jewish General Hospital (CA)
- Southlake Regional Health Center (CA)
- Flinders Medical Centre (AU)
- St Vincent's Hospital Melbourne (AU)
- Institute for Musculoskeletal Health (AU)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Centre Hospitalier de l’Université de Montréal (CA)
- The University of Texas Health Science Center (US)
- McGill University (CA)
- The University of Adelaide (AU)
- Université de Montréal (CA)
Publication Details
- Journal
- BMC Rheumatology
- Published
- 2026-08-20
- DOI
- https://doi.org/10.1186/s41927-026-00674-4
- Primary Topic
- Systemic Sclerosis and Related Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Mallinckrodt Pharmaceuticals
- Fresenius Kabi
- Dr. Fooke Laboratorien
- Scleroderma Society of Ontario
- Fonds de recherche du Québec
- Canadian Institutes of Health Research
- Lady Davis Institute for Medical Research
- Janssen Canada
- Canadian Arthritis Network
- Euroimmun Medizinische Labordiagnostika
- Boehringer Ingelheim Canada