ANTI-NOR90 ANTIBODIES IN THE SETTING OF CONNECTIVE TISSUE DISEASE: CLINICAL SIGNIFICANCE AND COMPARISON WITH A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

Background: Anti-NOR90 antibodies are directed against a 90-kD nucleolar protein located in the nucleolus organizing regions (NORs), mainly described in systemic sclerosis (SSc) [1, 2, 3] but reported also in other rheumatologic and oncologic diseases [4, 5, 6]. The clinical correlates of anti-NOR90 antibodies are still to be defined because the cohorts described thus far include a low number of patients. Objectives: To describe the characteristics of a large cohort of anti-NOR90 antibodies positive patients and compare them with a matched cohort of SSc patients negative for anti-NOR90 antibodies. Methods: A retrospective analysis was performed on patients positive for anti-NOR90 antibodies referring to participating centres. The concomitant positivity for anti-RNA polymerase III, Th/To, PM-Scl, Ku, and PDGFR antibodies was an exclusion criterion. In all cases the diagnoses, the different organ involvement and related clinical, instrumental and laboratory characteristics were evaluated. The EUROLINE SystemicSclerosisProfile kit from Euroimmun (Lübeck, Germany) was used to detect anti-NOR90 antibodies. Results: We included 101 patients positive for anti-NOR90 (M/F=13/88, mean age 52.5 years). They were mainly classified as SSc (n=38), undifferentiated connective tissue disease (UCTD) (n=21), interstitial pneumonia with autoimmune features (IPAF) (n=11) (graph 1). The most frequent clinical manifestations were arthralgias (n=72), Raynaud’s phenomenon (RP) (n=58), sicca syndrome (n=49), ILD (n=40), puffy fingers (n=32), arthritis (n=30), and limited skin sclerosis (n=24). Anti-NOR90 antibodies were associated with anti-Ro52 antibodies in the 16% of cases, with anticentromere antibodies in the 7% of cases, and with anti-Scl70 in the 5% of cases. After excluding these patients, and considering the isolated anti-NOR90 positivity, 12 patients had SSc, 35 UCTD, and 11 IPAF. The most frequent clinical manifestations were arthralgias (n=40), RP (n=37), and sicca syndrome (n=21). Compared to 242 matched SSc without anti-NOR90 antibodies, patients with anti-NOR90 had more frequently joint manifestations and sicca syndrome and less frequently all vasculopathic manifestations (RP, telangiectasias, pitting scars, acral ulcers), dysphagia and fibromyalgia. Conclusion: Our study shows that anti-NOR90 antibodies are more commonly observed in females, and clinically associated with the occurrence of arthritis/arthralgias, sicca syndrome and RP. In more than the 50% of cases they may be found with other autoantibodies, such as the anti-Ro52, the anticentromere, and the anti-Scl70 antibodies. Anti-NOR90 seems to play an accompanying role in the context of CTDs, without strong influence on the clinical phenotype expression of the underlying CTD. REFERENCES: [1] Rodriguez-Sanchez et al ., Anti-NOR 90. A new autoantibody in scleroderma that recognizes a 90-kDa component of the nucleolus-organizing region of chromatin, 1987. [2] Hamaguchi et al., Clinical and immunologic predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies, 2015. [3] Liaskos et al., Disease-related autoantibody profile in patients with systemic sclerosis, 2017. [4] Imai et al., Immunocytochemical characterization of human NOR-90 (upstream binding factor) and associated antigens reactive with autoimmune sera. Two MR forms of NOR-90/hUBF autoantigens, 1994. [5] Fujii et al., Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patients with rheumatic diseases, by recombinant autoantigen-based assays, 1996. [6] Yamashita et al., Clinical significance of anti-NOR90 antibodies in systemic sclerosis and idiopathic interstitial pneumonia, 2021. Figure 1. Disclosure of Interests: None declared Citation: , volume 81, supplement 1, year 2022, page 725Session: Scleroderma, myositis and related syndromes (POSTERS only)