Repost: Intraarticular Glucocorticoids in Oligoarticular JIA

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Association of the –173 SNP of the Macrophage Migration Inhibitory

Factor (MIF) Gene with Response to Intraarticular Glucocorticoids in

Oligoarticular JIA

Purpose. To evaluate the significance of the MIF -173 SNP in

oligoarticular JIA. MIF is a proinflammatory cytokine with the unique

ability to override the inhibitory effect of glucocorticoids on the

immune and inflammatory response.

A SNP (G/C) at position -173 of the MIF gene has been identified, shown

to be functionally relevant and to be associated with JIA.

In systemic JIA, patients carrying the MIF -173*C allele have higher

serum and SF levels of MIF, demonstrating the functional relevance of

this SNP, and show a poorer response to glucocorticoid treatment and

poor prognosis.

Methods. 85 patients with oligoarticular JIA were studied. The MIF -173

SNP was typed by SNAPshot. MIF levels were measured by ELISA.

Association with the frequency of uveitis, extension of articular

involvement and with long-term outcome was evaluated in patients with a

follow-up > 5 years (n=47).

Association with the duration of the clinical response to

glucocorticoids was evaluated in 43 patients for a total of 254

intraarticular injections of triamcinolone exacetonide (TXA).

Results. While the -173 MIF genotype was not associated with serum MIF

levels, patients carrying a MIF -173*C allele had synovial fluid MIF

levels significantly higher than those of G/G homozygous.

The frequency of patients with uveitis and of patients with a

polyarticular course was not different between patients carrying a MIF

-173*C allele and G/G homozygous.

At last visit the number of joints with active arthritis, the CHAQ

score, the number of joints with limited range of motion were comparable

between patients carrying a MIF -173*C allele and G/G homozygous.

The duration of clinical response to intraarticular TXA (months with no

clinical evidence of synovitis) was significantly shorter in patients

carrying a MIF -173*C allele (median: 6 months; range 1-39), than in G/G

homozygous (median: 9 months; range 2-62).

Conclusion. Patients carrying the MIF -173*C allele have higher synovial

levels of MIF, demonstrating the functional relevance of this SNP in

oligoarticular JIA.

In contrast with the findings in systemic JIA, patients with

oligoarticular JIA carrying the MIF -173*C allele do not have a worse

long-term prognosis.

The -173*C allele is associated with a shorter response to

intraarticular TXA in keeping with the role of MIF as a

counter-regulator of glucocorticoids effects.

This finding suggests that the -173 MIF SNP is a genetic predictor of

the response to intraarticular glucocorticoids in oligoarticular JIA.

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Fabrizio De Benedetti1, Marina Vivarelli2, Lamb3, Cristina

Meazza2, Flaminia Muratori1, Stefania Cioschi1, betta Cortis1,

Angelo Ravelli4, Alberto i4, le Donn3. 1IRCCS Ospedale

Pediatrico Bambino Gesù, Roma, Italy; 2IRCCS San Matteo, Pavia, Italy;

3ARC/EU, Manchester, United Kingdom; 4IRCCS G Gaslini, Genova, Italy