Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Genetic and Clinical Correlates of Anti-Fibrillarin (U3-RNP) Auto-Antibodies in African Americans with Systemic Sclerosis.

Sharif2,  Roozbeh, Fritzler4,  Marvin J., Reveille3,  John D., Assassi1,  Shervin, Mayes5,  Maureen D., Arnett6,  Frank C.

Univ of Texas Health Science, Houston, TX
Univ of Texas Health Science Center at Houston, Houston, TX
Univ Texas Health Sci Ctr, Houston, TX
University of Calgary, Calgary, AB, Canada
University of Texas-Houston, Houston, TX
UT Medical School, Houston, TX

Background:

Previous studies have suggested that anti-fibrillarin (U3-RNP) autoantibodies (AFA) are specific for systemic sclerosis (SSc) and occur more frequently in African Americans (AA) and men. A better prognosis in AAs with AFA also has been reported. The aim of this study was to investigate the associations of clinical features and human leukocyte antigen (HLA) class II alleles among AFA positive AAs with SSc and compare it with the AFA negative AA patients and unaffected AA controls.

Methods:

Between 1990 and 2010, 74 AA patients were enrolled in the ongoing observational cohort studies of AA patients, at our institution. Genetic characteristics, autoantibody profile, and clinical manifestations were examined. AFAs were determined by immunoprecipitation of the full length radiolabeled recombinant protein. HLA class-II (DRB1, DQA1, and DQB1) alleles were oligotyped or sequenced in AA patients (n=74) and AA controls (n=263). We used chi-square, Fisher's exact test, and student's t-test for comparative studies. We compared allelic frequencies between AFA positive (n=30) and negative (n=44) AAs, and subsequently with unaffected AA normal controls.

Results:

The mean age of AA patients with SSc was 47.7 (±13.4) years. Sixty one (61; 82.4%) were female and 52 (70.2%) had diffuse disease. There were no significant differences in gender and disease type (diffuse versus limited SSc). There were no significant differences in gastrointestinal, cardiac, and renal SSc between patients with and without AFA. Significant results are described in Table 1.

Conclusions:

These findings imply a strong association between HLA-DRB1*08, DRB1*0804, DRB1* 1302, DQB1*0301 and having two of three DQB1 alleles HLA-DQB1*0301, 0602, and 0604 with AFA in AA patients with SSc. This subset of SSc patients had less musculoskeletal involvement and secondary Sjögren's disease. DQB1*0301/0602/0604†P-value3.35 (1.10, 10.22)P-value5.67 (2.50, 12.90) Comparison between AFA positive (n=30) and AFA negative patients (n=44)Comparison between AFA positive and unaffected AA controls (n=263) P-valueOR (CI)P-valueOR (CI) DRB1*080.0313.35 (1.10, 10.22)<0.0015.67 (2.50, 12.90) DRB1*0804NS*<0.0015.81 (2.37, 14.25) DRB1*1302NS*0.0074.39 (2.28, 9.36) DQA1*01NS*0.0030.27 (0.11, 0.66) DQB1*0301NS*0.0122.90 (1.18, 7.38) DQB1*0301/0602/0604†0.0084.39 (1.45, 13.31)0.0023.69 (1.60, 8.49) Arthritis0.0050.13 (0.01, 0.69)N/AJoint contractures0.0360.34 (0.11, 1.04)N/AMyositis0.044N/AN/ALoss of digital pulp0.0110.27 (0.08, 0.85)N/ASclerodactyly0.032N/AN/ASjögren's syndrome0.0240.22 (0.04, 0.99)N/A

 Comparison between AFA positive (n=30) and AFA negative patients (n=44)Comparison between AFA positive and unaffected AA controls (n=263)
 P-valueOR (CI)P-valueOR (CI)
DRB1*080.0313.35 (1.10, 10.22)<0.0015.67 (2.50, 12.90)
DRB1*0804NS* <0.0015.81 (2.37, 14.25)
DRB1*1302NS* 0.0074.39 (2.28, 9.36)
DQA1*01NS* 0.0030.27 (0.11, 0.66)
DQB1*0301NS* 0.0122.90 (1.18, 7.38)
DQB1*0301/0602/0604†0.0084.39 (1.45, 13.31)0.0023.69 (1.60, 8.49)
Arthritis0.0050.13 (0.01, 0.69)N/A 
Joint contractures0.0360.34 (0.11, 1.04)N/A 
Myositis0.044N/AN/A 
Loss of digital pulp0.0110.27 (0.08, 0.85)N/A 
Sclerodactyly0.032N/AN/A 
Sjögren's syndrome0.0240.22 (0.04, 0.99)N/A 
* NS: not significant;†having two or more of these alleles

To cite this abstract, please use the following information:
Sharif, Roozbeh, Fritzler, Marvin J., Reveille, John D., Assassi, Shervin, Mayes, Maureen D., Arnett, Frank C.; Genetic and Clinical Correlates of Anti-Fibrillarin (U3-RNP) Auto-Antibodies in African Americans with Systemic Sclerosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1216
DOI: 10.1002/art.28982

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