Abstract
The objectives of this study were to determine genotypic and allelic frequencies of macrophage migration inhibitory factor (MIF) gene −173 G/C polymorphism in patients with juvenile rheumatoid arthritis (JRA) and to evaluate the association of the MIF −173 C allele with the outcome of JRA. Genomic DNA was collected from 67 JRA patients and 153 healthy individuals. To evaluate the association of the MIF −173 polymorphism with the outcome, we analyzed the data concerning the treatment regimen, duration of glucocorticoid treatment, score on the childhood health assessment questionnaire (C-HAQ) and the number of joints with active arthritis. Nonsignificant differences were observed between the study and control groups in the distribution of genotype and allele frequencies of the MIF gene −173 G/C polymorphism. In JRA patients, carrying a MIF −173 C allele, the number of disease modifying antirheumatic drugs required for the treatment was more, the duration of glucocorticoid treatment was significantly longer, and at the last visits the C-HAQ scores and the number of joints with active arthritis were significantly higher. MIF gene −173 C allele frequency did not differ between the controls and JRA patients. MIF −173 C allele did not confer increased susceptibility to JRA in our study group. Carriage of the MIF −173 C allele was found to be a strong predictor of poor outcome in all types of JRA.
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Brewer EJ, Bass J, Baum J et al (1977) Current proposed revision of JRA criteria. Arthritis Rheum 20:195–199
Schaller JG (1997) Juvenile rheumatoid arthritis. Pediatr Rev 18:337–349
Swope MD, Lolis E (1999) Macrophage migration inhibitory factor: cytokine, hormone or enzyme. Rev Physiol Biochem Pharmacol 139:1–32
De Benedetti F, Meazza C, Vivarelli M, Rossi Federice, Pistorio A, Lamb R, Lunt M, Thomson W, the British Paediatric Rheumatology Study Group, Ravelli A, Rachelle Donn, Martini A (2003) Functional and prognostic relevance of the −173 polymorphism of the macrophage migration inhibitory factor gene in systemic onset juvenile idiopathic arthritis. Arthritis Rheum 48:1398–1407
Donnelly SC, Bucala R (1997) Macrophage migration inhibitory factor: a regulator of glucocorticoid activity with a critical role in inflammatory disease. Mol Med Today 3:502–507
Meazza C, Pignatti P, Magni-Manzoni S, Martini A, de Benedetti F (2000) Increased levels of macrophage migration inhibitory factor in patients with juvenile idiopathic arthritis. Arthritis Rheum 43:356
Berdeli A, Mir S, Ozkayin N, Serdaroglu E, Tabel Y, Cura A (2005) Association of macrophage migration inhibitory factor −173 C allele polymorphism with steroid resistance in children with nephritic syndrome. Pediatr Nephrol (in press)
Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, Wolfe F, Gregersen PK, Bucala R (2002) A functional promoter polymorphism of macrophage migration inhibitory factor gene associated with disease severity in rheumatoid arthritis. Genes Immun 3:170–176
Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M et al (2002) Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile rheumatoid arthritis. Arthritis Rheum 46:2402–2409
Petty RE, Southwood TR, Baum J, Bhettay E, Glass E, Glass DN, Manners P et al (1998) Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban J Rheumatol 25:1991–1994
Dempster H, Porepa M, Young N, Feldman BM (2001) The clinical meaning of functional outcome scores in children with juvenile arthritis. Arthritis Rheum 44:1768–1774
Fantini F, Gerloni V, Gattinara M et al (1996) Remission in juvenile chronic arthritis: a cohort study in 506 consecutive cases. American College of Rheumatology, 60th National Meeting October 17–22, Orlando FL
Spiegel LR, Schneider R, Lang BA, Birdi N, Silverman ED, Laxer RM, et al (2000) Early predictors of poor functional outcome in systemic onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum 43:2402–2409
Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M et al (1996) An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci USA 93:7849–7854
Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T et al (1995) MIF as a glucocorticoid-induced modulator of cytokine production. Nature 377:68–71
Gäre BA (1999) Juvenile arthritis: who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatol 17:367–374
Peterson LS, Mason T, Nelson AM, O’Fallon WM, Gabriel SE (1997) Psychosocial outcomes and health status of adults who have had juvenile rheumatoid arthritis: a controlled, population-based study. Arthritis Rheum 40:2235–2240
Baugh JA, Bucala R (2002) Macrophage migration inhibitory factor. Crit Care Med 30:27–35
Lolis E (2001) Glucocorticoid counterregulation: macrophage migration inhibitory factor as a target for drug discovery. Curr Opin Pharmacol 1:662–668
De Jong YP, Abadia-Molina Ac, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA et al (2001) Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol 2:1061–1066
Kitaichi N, Kotake S, Sasamoto Y, Namba K, Matsuda A, Ogasawara K, et al (1999) Development of macrophage migration inhibitory factor in the sera of patients with uveitis. Invest Ophtalmol Vis Sci 40:247–250
Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M et al (1999) Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum 42:1601–1608
Brown FG, Nikolic-Paterson DJ, Hill PA, Isbel NM, Dowling J, Metz CM et al (2002) Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis. J Am Soc Nephrol 13:7–13
Niino M, Ogata A, Kikuchi S, Tashiro K, Nishihira J (2000) macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro_Behçet’s disease. J Neurol Sci 179:127–131
Donn RP, Shelley E, Ollier WER, Thomson W, and the British Pediatric Rheumatology Study Group (2001) A novel 5′, flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 44:1782–1785
Ilowite NT (2002) Current treatment of juvenile rheumatoid arthritis. Pediatrics 109:109–115
Gregersen PK, Bucala R (2003) Macrophage migration inhibitory factor, MIF alleles, and the genetics of inflammatory disorders: incorporating disease outcome into the definition of phenotype. Arthritis Rheum 48:1171–1176
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Berdeli, A., Özyürek, A.R., Ülger, Z. et al. Association of macrophage migration inhibitory factor gene −173 G/C polymorphism with prognosis in turkish children with juvenile rheumatoid arthritis. Rheumatol Int 26, 726–731 (2006). https://doi.org/10.1007/s00296-005-0062-7
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DOI: https://doi.org/10.1007/s00296-005-0062-7