Th2 cytokine genotypes are associated with a milder form of primary Sjogren's syndrome

Background: Immunohistological studies on salivary and lacrimal glands have yielded conflicting results on the Th1/Th2 balance in primary Sjogren's syndrome (pSS). Objective: To establish whether pSS is a Th1 or Th2 directed autoimmune disease by analysing the polymorphism of the genes encoding for cytokines involved in the regulation of Th1/Th2 differentiation. Methods: The polymorphisms of the genes encoding for interleukin 4 (IL4) -590 C/T, interleukin 13 (IL13) + 2044 G/A, and interferon gamma (IFNG) + 874 T/A were analysed in 63 white Finnish patients with pSS ( 61 female, two male) and in 63 healthy controls. The clinical and immunological data on the pSS patients were analysed in relation to these cytokine gene polymorphisms. Results: There were no significant differences in the genotype or allele frequencies of IL4 2590, IL13 + 2044, or IFNG + 874 between pSS patients and controls. The erythrocyte sedimentation rate and concentrations of serum IgA and serum beta 2 microglobulin were lower in pSS patients carrying the IL4 -590 T allele or the IL13 + 2044 A allele than in those not carrying the respective alleles. The IL4 -509 T allele and IL13 + 2044 A allele carriers less often had purpura than the corresponding non-carriers. Conclusions: The frequencies of the cytokine genotypes regulating Th1/Th2 differentiation did not differ between pSS patients and controls. However, the presence of cytokine genotypes with increased susceptibility to atopic and other Th2 diseases was associated with signs of a milder form of pSS. This finding would favour a hypothesis envisaging pSS as primarily a Th1 mediated autoimmune disease.