Macrophage migration inhibitory factor (MIF) and oligoarticular juvenile idiopathic arthritis (o-JIA): association of MIF promoter polymorphisms with response to intra-articular glucocorticoids.
OBJECTIVE
To address the clinical relevance of macrophage migration inhibitory factor (MIF) promoter polymorphisms in oligoarticular juvenile idiopathic arthritis (o-JIA) by evaluating their associations with serum and SF MIF levels, with response to intra-articular glucocorticoid injections and with outcome of the disease.


METHODS
Seventy-five Caucasian patients with o-JIA were studied. Alleles of the -794 CATT variable number of tandem repeats (VNTR) and of the -173 G/C single nucleotide polymorphism (SNP) were identified by capillary electrophoresis following fluorescently labelled PCR and by allelic discrimination assay, respectively. MIF levels were measured by ELISA. The association of MIF promoter polymorphisms with polyarticular extension, Childhood Health Assessment Questionnaire (CHAQ) score at the last follow-up visit and occurrence of chronic anterior uveitis was evaluated only in patients with a follow up > 5 years.


RESULTS
Neither of the MIF promoter polymorphisms was associated with serum MIF levels, nor with the long-term outcome of o-JIA. The -173 G/C SNP was significantly associated with both SF MIF levels and duration of response to intra-articular glucocorticoid injection. Carriers of a MIF -173 C allele were 4 times more likely to relapse within 3 months. No association was found between the different MIF CATT alleles and both SF MIF levels and duration of response to intra-articular glucocorticoids.


CONCLUSIONS
Our study shows the clinical relevance of the MIF -173 G/C SNP in o-JIA and suggests that the -173 C allele may represent a predictor of poor response to intra-articular glucocorticoid treatment.
Vivarelli
M
M
Direzione Scientifica, Pediatria II Reumatologia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
D'Urbano
L E
LE
Insalaco
A
A
Lunt
M
M
Jury
F
F
Tozzi
A E
AE
Ravelli
A
A
Martini
A
A
Donn
R
R
De Benedetti
F
F
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007270:Injections, Intra-Articular; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D013582:Synovial Fluid / Q000378:metabolism; D016896:Treatment Outcome
D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human