IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction

Objective. To evaluate the occurrence of variants of the interleukin 4 (IL- 4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (R A) and their possible contribution to joint destruction. Methods. Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patient s and 104 controls. Clinical indices of disease activity, disability and jo int destruction and plasma levels of IL-I beta, IL-1Ra and sCD23 were asses sed to evaluate a possible functional effect. Results. Carriage of the rare IL-4(2) allele was higher in patients with no n-destructive RA (40%) than in those with destructive RA (22.3%: odds ratio = 1.9. 95% confidence interval 1.1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less j oint destruction, assessed by the Larsen wrist index (P = 0.004) and a lowe r erythrocyte sedimentation rate (P = 0.04). A significantly higher carriag e rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was no t over-represented. Plasma levels of IL-1 beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different all eles. Conclusion. This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker e arly in the course of the disease.