Antifibrillarin Antibodies Are Associated with Native North American Ethnicity and Poorer Survival in Systemic Sclerosis

Abstract

Objective To examine the clinical correlates and survival in patients with anti-fibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States of America. Methods Baseline clinical data from the prospective cohorts [Canadian Scleroderma Research Group (CSRG), the Australian Scleroderma Cohort Study (ASCS) and the American Genetics versus Environment in Scleroderma Outcome Study (GENISOS)] were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available systemic sclerosis profile line immunoassay (LIA), regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Furthermore, a survival analysis was performed by Cox regression analysis. Results A total of 1506 SSc patients with complete serological profiles were included in the study. Fifty-two (3.5%) patients had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA positive compared to other ethnicities. After adjustment for demographic factors, diffuse involvement and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Furthermore, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11, 2.79, p=0.016). Conclusion In this large multinational SSc cohort, AFA was associated with Native American Ethnicity and was an independent predictor of mortality.

Quantification of Antifibrillarin (anti-U3 RNP) Antibodies: A New Insight for Patients with Systemic Sclerosis

“…This association of AFAs with disease severity was independent of the cutaneous form of the disease and remained significant when patients were matched according to their cutaneous form. We also observed a higher proportion of deceased patients in AFA-positive SSc patients, which is consistent with the decreased survival in AFA-positive patients reported in the literature [9,11].…”

“…Previous studies have described the clinical characteristics associated with AFAs in SSc patients [3][4][5][6][7][8][9][10][11][12]. The estimated frequency of AFAs ranges from 0 to 18.5% of SSc patients, with the highest prevalence found in Afro-American patients [10].…”

“…The estimated frequency of AFAs ranges from 0 to 18.5% of SSc patients, with the highest prevalence found in Afro-American patients [10]. AFAs are more frequent in male patients [4,7,9] and are associated with an early onset of the disease [8][9][10], a diffuse cutaneous form [8,9,11,13] and a decreased survival [9,11]. Numerous organ involvements are related to the presence of AFAs such as pulmonary hypertension [5,6,8,9], cardiac [7,11,14], gastrointestinal tract [3,5,9,11], peripheral vascular [9] and skeletal muscle involvement [5,8,9].…”

Evaluation of a novel particle-based multi-analyte technology for the detection of anti-fibrillarin antibodies

“…They also have been associated with certain HLA-DQB1 alleles, specific ethnicities, such as Afro-Caribbean origin, identify younger SSc patients, and display a higher prevalence of myositis [ 14 , 15 , 19 , 20 ]. It has also been reported that anti-fibrillarin antibodies were associated with native American ethnicity and were mortality independent predictors in those affected with SSc [ 21 ].…”

Overall mortality

“…Multivariate analyses of a pooled international cohort did not demonstrate an association of Native North American or Australian Aboriginal heritage with increased mortality. 34…”