HLA and self-limiting, unclassified rheumatism. A role for HLA-B35?

OBJECTIVE: To test the hypothesis of increased frequency of HLA-B35 in self-limiting, unclassified rheumatism (SUR). METHODS: Patients (n = 50) were included if they had swelling of one or more joints for more than 24 h and/or pain without trauma of 2 or more joints for one month or longer, and at least one of (1) history of joint swelling, (2) morning stiffness, (3) elevated erythrocyte sedimentation rate and/or C-reactive protein. Patients fulfilling diagnostic criteria sets of any rheumatic disease and patients with other identified diseases were excluded. Controls were 50 patients with rheumatoid arthritis (RA) and 199 healthy blood donors. RESULTS: HLA-B35 frequency (0.32) was significantly greater in SUR than in RA (0.14) and controls (0.17). HLA-DR4 frequency was significantly increased in HLA-B35 positive SUR, while that of HLA-DR1 was decreased (NS). Clinical characteristics of SUR were: history of atopy; transient, mono or oligoarticular synovitis and widespread, longlasting pain. HLA-B35 positive patients with SUR more often had hip, knee, or back pain than HLA-B35 negative patients. CONCLUSION: HLA-B35 frequency is increased in SUR, while HLA-DR1 frequency is not. A likely hypothesis of attenuated immune inflammation in SUR is further supported by results in juvenile RA, adult Still's disease, and a series of mild inflammatory arthritides, and by indirect evidence of decreased Th1 response and increased Th2 response in HLA-B35 positive patients with various conditions.

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.