Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review.

Background: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain.
Objectives: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort.
Methods: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023.
Results: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %.
Conclusion: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.
Competing Interests: Declaration of competing interest DIMA Alina: Nothing to disclose. VONK Madelon: Consultancy relationship with and/or research funding from and/or speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis. GARAIMAN Alexandru: Nothing to disclose. KERSTEN E Brigit: Nothing to disclose. BECVAR Radim: Nothing to disclose. TOMCIK Michal: Nothing to disclose. HOFFMANN-VOLD Anna-Maria: Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche; Consultant: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche; Grant/research support: Boehringer Ingelheim, Jannsen CASTELLVI Ivan: Speakers’ bureau: Boehringer, Janssen-Cilag, BMS, Roche, UCB; Consultant: Boehringer, Janssen-Cilag, Topandur. TANDAIPAN JAIME Jose Luis: Nothing to disclose. BRZOSKO Marek: Nothing to disclose. MILCHERT Marcin: Nothing to disclose. KRASOWSKA Dorota: Speakers’ bureau: Novartis, Abbvie, Elli Lilly; Consultant: Boehringer Ingelheim, Novartis, Janssen. MICHALSKA-JAKUBUS Małgorzata: Nothing to disclose. AIRO Paolo: Consulting fees, honoraria for lectures, presentations, or educational events, support for attending meetings and/or travel from: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag MATUCCI-CERINIC Marco: Speakers’ bureau: Biogen, Sandoz, Boehringer, Lilly, Galapagos; Grant/research support: MSD, Janssen; BRUNI Cosimo: Consultant: Boehringer Ingelheim; Grant/research support: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC); Novartis Foundation for medical-biological research, EMDO Foundation; Educational grants: AbbVie, Wellcome Trust. IUDICI Michele: Nothing to disclose. DISTLER Jorg: Nothing to disclose. GHEORGHIU Ana-Maria: Speakers’ bureau: Sandoz, Boehringer Ingelheim, Ewopharma; Consultant: Boehringer Ingelheim. POORMOGHIM Hadi: Nothing to disclose. MOTTA Francesca: FM had consulting fees from Thermo Fisher. DE SANTIS Maria: Nothing to disclose. PARVU Magda: Nothing to disclose. DISTLER Oliver: OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Research Grants: BI, Kymera, Mitsubishi Tanabe MIHAI Carina: CM received consulting fees and/or honoraria from Boehringer Ingelheim, Janssen Cilag AG, MED Talks Switzerland, Medbase, Mepha, Novartis, and PlayToKnow AG, and congress support from Boehringer Ingelheim and Roche.
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