Association of transforming growth factor beta1 and tumor necrosis factor alpha polymorphisms with anti-SSB/La antibody secretion in patients with primary Sjögren's syndrome.

Objective: To determine whether cytokine gene polymorphisms of interferon-gamma (IFNgamma), interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) predispose subjects to the development of primary Sjögren's syndrome (SS).

Methods: Single-base-exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American-European Consensus Group criteria, as well as in 96 unrelated healthy subjects.

Results: The frequency of the TNF-308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti-SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA-DRB1*03 on disease or on anti-SSB antibody secretion. The frequency of allele C at codon 10 of TGFbeta1 was strongly increased in the subgroup of patients with anti-SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti-SSB. The IL-10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL-10 allele and genotype frequencies were not significantly different. No association was found between IL-6 or IFNgamma polymorphisms and primary SS.

Conclusion: TNF2 was associated with anti-SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGFbeta1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti-SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.