Background:The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation and malfunction in patients with systemic sclerosis (SSc)[1]. A variety of ANAs[2], including anti-centromere antibody, anti-topoisomerase I antibody, and anti-RNA polymerase III antibody, are associated with unique sets of disease manifestations and widely used in routine clinical practice for diagnosis, clinical subgrouping, risk stratification and prediction of future organ involvements and prognosis in SSc patients[3,4].Objectives:This study aimed to investigate the clinical features of SSc patients with negative ANAs in a European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) and Chinese Rheumatism Data Center (CRDC) multi-center cohort in China.Methods:Patients were prospectively recruited between April 2008 and June 2019 based on the EUSTAR database and CRDC multi-center cohort from 154 clinical centers nationwide, all of whom fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Antinuclear antibody testing result was intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those with negative ANAs. T-test and chi-square analysis were performed in the comparisons.Results:Antinuclear antibodies were detected in 2129 out of 2809 systemic sclerosis patients enrolled in the multi-center cohort and 4.2% of them were negative. There was significant difference between patients with negative and positive ANAs based on gender (29/60 vs 294/1746, p<0.001). The presence of Raynaud’s phenomenon is less common (71.8% vs 99.8%, p<0.001) in the ANA-negative patients. In addition, compared with ANA-positive patients, the incidence of certain critical organ involvements, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006) were significantly lower in ANA-negative patients than in the positive group. The proportion of IgG elevation, an indicator of disease activity and severity of inflammation, was significantly lower in the ANA-negative patients than that in the positive group (14.3% vs 41.2%, p<0.001), while no significant differences were found in other inflammatory indicators and skin scores.Conclusion:This study describes the clinical features of SSc patients with negative ANAs, which have been rarely mentioned or focused in existing studies. Antinuclear antibody is proved to be strongly associated with the clinical manifestations of systemic sclerosis patients and ANA-negative SSc patients tend to be in relatively milder conditions, including a less common involvement of critical organs and a more temperate inflammatory severity.References:[1]Seri, Jeong, Dahae, et al. Diagnostic value of screening enzyme immunoassays compared to indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis. [J]. Seminars in arthritis and rheumatism, 2018.[2]Hesselstrand, R. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis[J]. Rheumatology, 2003, 42(4):534-540.[3]Behmanesh F, Amin R, Khajedaluee M, et al. Autoantibody Profile in Systemic Sclerosis[J]. Acta Medica Iranica, 2010, 48(1):12-20.[4]Hachulla E, Dubucquoi S. Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and the prognosis of systemic sclerosis. [J]. La Revue de Médecine Interne, 2004, 25(6):442-447.Disclosure of Interests:None declared
Prevalence of autoantibodies to cellular cytoplasmic and mitotic antigens in routine antinuclear antibody reporting: Implementation of international consensus on antinuclear antibodies patterns guidelines