Proinflammatory Cytokine Mutation Linked to Juvenile Rheumatoid Arthritis

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Proinflammatory Cytokine Mutation Linked to Juvenile Rheumatoid Arthritis

By Faith Reidenbach

NEW YORK (Reuters Health) Oct 23 - A single-nucleotide polymorphism in the

macrophage migration inhibitory factor (MIF) gene, identified last year by a

UK research team, has now been demonstrated to confer increased

susceptibility to juvenile rheumatoid arthritis (JRA).

MIF, a proinflammatory cytokine, counteracts the antiinflammatory actions of

glucocorticoids, Dr. le Donn, of the University of Manchester, and

colleagues note in the September issue of Arthritis and Rheumatism. They

explain that " MIF, together with endogenous glucocorticoids, is central to

determining the magnitude, and possibly the chronicity, of an immune

inflammatory response. "

In previous research, Dr. Donn's group found a G-to-C substitution at

position -173 in one region of the MIF gene. The team showed that this

polymorphism was associated with systemic-onset JRA.

In the new study, Dr. Donn and her associates analyzed the MIF-173 genotype

of 526 JRA patients and 259 controls. They demonstrated that individuals

with a C allele were 1.9 times more likely to have JRA than those homozygous

for the G allele (p = 0.0002). All seven subgroups of JRA patients were at

increased risk.

" This suggests that the effect of MIF-173*C is common to a shared feature of

the juvenile idiopathic arthritis subgroups, " the research team points out.

" This could be the ongoing inflammation that occurs within the synovial

joints of juvenile idiopathic arthritis patients. "

Among 53 control subjects, those with the C allele had significantly higher

serum MIF levels than those homozygous for G. " MIF protein levels have been

found to be increased in a diverse range of disease states, " Dr. Donn told

Reuters Health. " Understanding the genetic variation that correlates with

such expression will enhance the understanding, and potential treatment, of

these different pathologies. "

As an example, " tailoring of the dosage of glucocorticoids could be directed

by MIF genotype, " she said. " Also, the possible use of anti-MIF antibodies,

used synergistically with steroids, could be influenced by the prior

knowledge of an individual's MIF genotype. "

Arthritis Rheum 2002;46:2402-2409.