Abstract
Objective
To compare the frequencies of variants of TCRBV20S1 and TCRBV3S1 gene segments in patients with systemic sclerosis (SSc) and in controls. The null allele (allele 2) of TCRBV20S1 is associated with reduced levels of Vβ20+ T-cells in the peripheral blood, while allele 1 of TCRBV3S1 is related to a low frequency of Vβ3.1+ T-cells.
Methods
One hundred thirty patients with SSc and 118 healthy volunteer controls were genotyped for TCRBV20S1, and 117 patients and 85 controls were genotyped for TCRBV3S1 variants by PCR-RFLP. Patients underwent clinical evaluation, serology, pulmonary function tests, high resolution computed tomography, and Doppler echocardiography.
Results
The genotypic frequencies of TCRBV20S1 were 0.46 (allele 1/allele 1), 0.43 (allele 1/allele 2), and 0.11 (allele 2/allele 2) in SSc patients; in controls the frequencies were 0.70, 0.26, and 0.04, respectively (p < 0.001). The Mantel-Haenszel odds ratio (stratified by race and sex) of the allele 2 carrier state was 3.88 (95% CI 1.94 to 7.75). The allelic and genotypic frequencies of the TCRBV3S1 gene segment did not differ significantly in patients and controls. However, among patients, allele 1 (TCRBV3S1) carriers had a higher prevalence of interstitial lung disease (adjusted p = 0.032).
Conclusion
The null allele of the TCRBV20S1 and the allele 1 of TCRBV3S1 gene segments may be considered risk factors for the development of SSc and interstitial lung disease, respectively, suggesting a protective role of Vβ20+ and Vβ3.1+ cells in the pathogenic immune responses in SSc.
Key Indexing Terms:Footnotes
-
M. Bredemeier, MD, PhD, Division of Rheumatology, Hospital de Clínicas de Porto Alegre; J.A.B. Chies, PhD, Adjunct Professor; A. Wieck, MSc, Genetics Department, Universidade Federal do Rio Grande do Sul; K.G. Capobianco, MD, PhD, Division of Rheumatology; E.H. Pitrez, MD, PhD, Division of Radiology; L.E.P. Rohde, MD, PhD; A.F.F. Pinotti, MD, MSc, Division of Cardiology; J.C.T. Brenol, MD, PhD, Associate Professor of Rheumatology; R.M. Xavier, MD, PhD, Divison of Rheumatology, Hospital de Clínicas de Porto Alegre, Associate Professor of Rheumatology, Universidade Federal do Rio Grande do Sul.
-
Supported in part by grants from Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA).
- Accepted for publication January 23, 2008.