RESEARCH - Severe disease in patients with RA carrying a mutation in the Mediterranean fever gene

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Ann Rheum Dis. 2005 Jul;64(7):1009-14.

Severe disease in patients with rheumatoid arthritis carrying a mutation in

the Mediterranean fever gene.

Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y.

Heller Institute of Medical Research, Sheba Medical Centre, Tel Hashomer

52621, Israel. yshinar@....

BACKGROUND: Pyrin is a newly recognised intracellular regulator of

inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause

of familial Mediterranean fever. OBJECTIVE: To determine if known mutations

of MEFV are associated with rheumatoid arthritis (RA) morbidity or can

modify RA severity. METHODS: The frequency of the three most common MEFV

mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients

with RA (74 women, 24 men) and compared with that in 100 healthy subjects

matched for origin. RA severity was determined using a new clinical score of

126 grades. The median severity score of mutation carrier and non-carrier

groups was compared after confounding measures were eliminated by logistic

regression. RESULTS: 17/98 (17%) patients with RA (all women) were

heterozygous for common MEFV mutations, predominantly E148Q (12 patients),

and one patient was homozygous for the V726A mutation. The overall mutation

rate was comparable between patients with RA and healthy subjects. Patients

carrying a mutation had a higher median severity score than the non-carrier

group (42 v 29, p = 0.0005). The logistic regression model assigned a

15-fold odds ratio for severe RA in carriers, after adjusting for sex,

presence of rheumatoid factor, age at onset, and disease duration (n = 97, p

= 0.01, 95% CI 1.74 to 128).

CONCLUSION: MEFV, and particularly the E148Q

mutation, is an independent modifier of the clinical manifestations of RA.

This is the second Th1-type autoimmune disease in which MEFV mutations have

been shown to aggravate the clinical status.

PMID: 15958759

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

5958759 & dopt=Abstract

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