Interleukin-10 promoter microsatellite polymorphisms are associated with response to long term treatment with etanercept in patients with rheumatoid arthritis

Heiko Schotte ^1*, Bernhard Schlter ², Susanne Drynda ³, Peter Willeke ¹, Nicola Tidow ², Gerd Assmann ², Wolfram Domschke ¹, Jörn Kekow ³ and Markus Gaubitz ¹

¹ Department of Medicine B, Mnster University Hospital, Germany
² Institute of Clinical Chemistry and Laboratory Medicine, Mnster University Hospital, Germany
³ Clinic of Rheumatology, University of Magdeburg, Germany

^* To whom correspondence should be addressed. E-mail: h.schotte{at}uni-muenster.de.

Accepted 22 August 2004

Abstract

Objective: To analyze the association of interleukin-10 (IL-10) promoter polymorphisms, that have been shown to be related to IL-10 secretion capacity, with the response to long-term treatment with etanercept in patients with rheumatoid arthritis (RA).

Methods: Fifty (50) patients with active RA were treated up to 4 years (median 39 months, range 3-52) with stable doses of etanercept as monotherapy. Therapy response was assessed as defined by the EULAR criteria in an intention-to-treat analysis with the last observation carried forward. IL-10 promoter microsatellite polymorphisms IL10.R and IL10.G were genotyped by fragment length analysis in patients and 189 ethnically, age- and sex-matched healthy controls. Haplotypes were reconstructed using a Bayesian, coalescent theory-based method with the PHASE software.

Results: The IL-10 microsatellite polymorphisms were not associated with susceptibility to RA. Upon comparison of patients with good treatment response (n=25) to patients with moderate (n=17) or no response (n=8) a significantly different distribution of the prevailing alleles R2, R3 and G9, G13, respectively, became evident. A good treatment response was associated with carriage of the R3 allele or the R3-G9 haplotype, whereas the allele G13 and the haplotype R2-G13 predominated in patients with moderate or no response.

Conclusion: Genotyping of the IL-10 promoter microsatellites may be useful in the prognostic estimation of the clinical response to etanercept in patients with RA. The high prevalence of the presumptive IL-10 low-producer allele R3 in patients with a favorable response suggests that IL-10 promotes disease activity in RA under the specific condition of TNF antagonization.

Keywords: etanercept, interleukin-10, promoter microsatellite polymorphisms, rheumatoid arthritis

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