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Abstract Number: 2916

Anti-Fibrillarin Antibodies Are Associated With More Severe Gastrointestinal Involvement and Poorer Survival

Shervin Assassi1, Marie Hudson2, Maureen D. Mayes3, Jennifer Walker4, Murray Baron5,6, Wendy Stevens7, Karen Patterson8, Tiffany Graham1, Solene Tatibouet9, James Wick10, Matt Stephenson11 and Marvin J. Fritzler11, 1Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, 2Rheumatology, Lady David Institute for Medical Research and Jewish General Hospital, Montreal, QC, Canada, 3University of Texas Health Science Center at Houston, Houston, TX, 4Flinders Medical Centre, Adelaide, Australia, 5McGill University, Montreal, QC, Canada, 6MCGill University, Montreal, QC, Canada, 7Rheumatology, St Vincent's Hospital, Melbourne, Australia, 8Institute of Medical and Veterinary Science, North Adelaide, Australia, 9Jewish General Hospital, McGill University, Montreal, QC, Canada, 10Department of medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada, 11Medicine, University of Calgary, Calgary, AB, Canada

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Antibodies, clinical research and scleroderma

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Session Information

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s-Clinical Aspects and Therapeutics III

Session Type: Abstract Submissions (ACR)

Background/Purpose: Anti-fibrillarin (U3-RNP) antibodies (AFA) are a relatively specific biomarker for systemic sclerosis (SSc).  Previous studies have indicated a higher prevalence of AFA among African American patients.  The examination of demographic and clinical correlates of AFA has been hampered by its low prevalence. Our objective was to examine the clinical correlates of AFA in a large study population consisting of three well-characterized SSc cohorts from Canada, Australia, and the USA.

Methods: A total of 1596 SSc patients enrolled in the Canadian Scleroderma Research Group (CSRG), the Australian Scleroderma Interest Group (ASIG), and the Genetics versus Environment In Scleroderma Outcome Study (GENISOS) were included in this study. AFA were determined by a line immunoassay (EUROLINE, Euroimmun, Lübeck, Germany). In addition to demographic data, associations with clinical data including modified Rodnan Skin Score (mRSS), history of digital ulcers/pits, calcinosis, arthritis, telangiectasia, scleroderma renal crisis, gastrointestinal (GI), pulmonary manifestations and pulmonary function test parameters were examined.  An association with the overall mortality was also examined by Cox regression analysis

Results: The mean (± SD) age at enrollment and disease duration were 55 (± 12.8) and 9.5 (± 9.2) in the overall study population. Diffuse cutaneous involvement was present in 606 patients (38.6%). The study population was multi-ethnic consisting of 1,106 white, 71 African descent, 90 Hispanic, 48 Asian, and 39 Native North-American, and 8 Australian Aboriginal patients.  A total of 52 patients (3.3%) had AFA. These antibodies were more common among African descent (OR: 2.92, p= 0.033) and Native North-American patients (OR=4.4, p=0.008).   

In the multivariate analysis after adjustment for age at enrollment and ethnicity, patients with AFA had more frequently bacterial overgrowth requiring antibiotics (OR=2.5, p=0.048). There were also trends for an association with diffuse cutaneous involvement (OR=1.78, p=0.057) gastroesophageal reflux disease (OR=2.56, p=0.074) and need for parenteral nutrition (OR=3, p=0.099).

In Cox regression analysis after adjustment for age at enrollment and ethnicity, patients with AFA had poorer survival (HR: 2.36, p<0.001).  This relationship remained significant even after addition of disease type to the model (HR: 2.28, p<0.001).

AFA were not associated with vascular, renal, or pulmonary manifestations of disease.

Conclusion: This large international study confirmed the association of AFA with African decent ethnicity and GI involvement.  The large, well-characterized study population allowed us to make the following novel observations: AFA are associated with Native North-American ethnicity, diffuse cutaneous involvement, and poorer survival.  The more severe GI involvement might explain partially the observed poorer survival in this serological subtype of SSc patients.


Disclosure:

S. Assassi,
None;

M. Hudson,
None;

M. D. Mayes,
None;

J. Walker,
None;

M. Baron,
None;

W. Stevens,
None;

K. Patterson,
None;

T. Graham,
None;

S. Tatibouet,
None;

J. Wick,
None;

M. Stephenson,
None;

M. J. Fritzler,

Inova Diagnostics, Inc.,

5.

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