IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjögren's syndrome and rheumatoid arthritis

The gene encoding interleukin-1 receptor antagonist (IL-1ra) has a variable allelic polymorphism. The IL1RN*2 allele was recently described as a factor of severity in several autoimmune diseases and was paradoxically associated with increased production of IL-1ra by monocytes in vitro. We studied this polymorphism in 36 patients with possible or definite primary Sjögren's syndrome and found that IL1RN*2 was significantly more frequent in the definite than in the possible form. In rheumatoid arthritis, the frequency of the allele was not different from that of controls. The serum levels of IL-1ra were markedly higher in Sjögren patients than in those of healthy subjects. By contrast, the salivary IL-1ra levels were decreased. Patients with the allele generally had lower salivary levels and higher serum levels than patients without the allele. In the group of patients with the definite syndrome, CRP and TGF-beta 1, two in vitro stimulators of IL-1ra production, were correlated with IL-1ra serum levels. Our results suggest that IL1RN*2 is a marker of more severe forms of Sjögren's syndrome. Its effect on salivary and serum IL-1ra may be distinct, suggesting separate regulatory mechanisms.