Association of transforming growth factor β1 and tumor necrosis factor α polymorphisms with anti‐SSB/La antibody secretion in patients with primary Sjögren's syndrome

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Abstract
Objective To determine whether cytokine gene polymorphisms of interferon‐γ (IFNγ), interleukin‐6 (IL‐6), IL‐10, tumor necrosis factor α (TNFα), and transforming growth factor β1 (TGFβ1) 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 TGFβ1 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 IFNγ 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 TGFβ1 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.