RESEARCH - IL-10 promoter microsatellite polymorphisms are associated with response to Enbrel in patients with RA

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Ann Rheum Dis. 2004 Sep 2 [Epub ahead of print]

Interleukin-10 promoter microsatellite polymorphisms are associated with

response to long term treatment with etanercept in patients with

rheumatoid arthritis.

Schotte H, Schluter B, Drynda S, Willeke P, Tidow N, Assmann G, Domschke

W, Kekow J, Gaubitz M.

Department of Medicine B, Mnster University Hospital, Germany.

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.

PMID: 15345504

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5345504 & dopt=Abstract

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