Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis

Fabrizio De Benedetti, Cristina Meazza, Marina Vivarelli, Federica Rossi, Angela Pistorio, Rebecca Lamb, Mark Lunt, Wendy Thomson, M. Abinun, M. Becker, A. Bell, A. Craft, E. Crawley, J. David, H. Foster, J. Gardener-Medwin, J. Griffin, A. Hall, M. Hall, A. Herrick & 14 others P. Hollingworth, L. Holt, S. Jones, G. Pountain, C. Ryder, T. Southwood, I. Stewart, H. Venning, L. Wedderburn, P. Woo, S. Wyatt, Angelo Ravelli, Rachelle Donn, Alberto Martini

Research output: Contribution to journalArticle

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Abstract

Objective. To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods. A total of 136 patients with systemiconset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.

Original languageEnglish
Pages (from-to)1398-1407
Number of pages10
JournalArthritis and Rheumatism
Volume48
Issue number5
DOIs
Publication statusPublished - May 1 2003

Fingerprint

Macrophage Migration-Inhibitory Factors
Juvenile Arthritis
Genes
Alleles
Joints
Synovial Fluid
Articular Range of Motion
Italy
Glucocorticoids
Arthritis
Dideoxynucleotides
Intra-Articular Injections
Health
Capillary Electrophoresis
Rheumatology
Serum
Nucleotides
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. / De Benedetti, Fabrizio; Meazza, Cristina; Vivarelli, Marina; Rossi, Federica; Pistorio, Angela; Lamb, Rebecca; Lunt, Mark; Thomson, Wendy; Abinun, M.; Becker, M.; Bell, A.; Craft, A.; Crawley, E.; David, J.; Foster, H.; Gardener-Medwin, J.; Griffin, J.; Hall, A.; Hall, M.; Herrick, A.; Hollingworth, P.; Holt, L.; Jones, S.; Pountain, G.; Ryder, C.; Southwood, T.; Stewart, I.; Venning, H.; Wedderburn, L.; Woo, P.; Wyatt, S.; Ravelli, Angelo; Donn, Rachelle; Martini, Alberto.

In: Arthritis and Rheumatism, Vol. 48, No. 5, 01.05.2003, p. 1398-1407.

Research output: Contribution to journalArticle

De Benedetti, F, Meazza, C, Vivarelli, M, Rossi, F, Pistorio, A, Lamb, R, Lunt, M, Thomson, W, Abinun, M, Becker, M, Bell, A, Craft, A, Crawley, E, David, J, Foster, H, Gardener-Medwin, J, Griffin, J, Hall, A, Hall, M, Herrick, A, Hollingworth, P, Holt, L, Jones, S, Pountain, G, Ryder, C, Southwood, T, Stewart, I, Venning, H, Wedderburn, L, Woo, P, Wyatt, S, Ravelli, A, Donn, R & 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 and Rheumatism, vol. 48, no. 5, pp. 1398-1407. https://doi.org/10.1002/art.10882
De Benedetti, Fabrizio ; Meazza, Cristina ; Vivarelli, Marina ; Rossi, Federica ; Pistorio, Angela ; Lamb, Rebecca ; Lunt, Mark ; Thomson, Wendy ; Abinun, M. ; Becker, M. ; Bell, A. ; Craft, A. ; Crawley, E. ; David, J. ; Foster, H. ; Gardener-Medwin, J. ; Griffin, J. ; Hall, A. ; Hall, M. ; Herrick, A. ; Hollingworth, P. ; Holt, L. ; Jones, S. ; Pountain, G. ; Ryder, C. ; Southwood, T. ; Stewart, I. ; Venning, H. ; Wedderburn, L. ; Woo, P. ; Wyatt, S. ; Ravelli, Angelo ; Donn, Rachelle ; Martini, Alberto. / Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. In: Arthritis and Rheumatism. 2003 ; Vol. 48, No. 5. pp. 1398-1407.
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title = "Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis",
abstract = "Objective. To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods. A total of 136 patients with systemiconset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.",
author = "{De Benedetti}, Fabrizio and Cristina Meazza and Marina Vivarelli and Federica Rossi and Angela Pistorio and Rebecca Lamb and Mark Lunt and Wendy Thomson and M. Abinun and M. Becker and A. Bell and A. Craft and E. Crawley and J. David and H. Foster and J. Gardener-Medwin and J. Griffin and A. Hall and M. Hall and A. Herrick and P. Hollingworth and L. Holt and S. Jones and G. Pountain and C. Ryder and T. Southwood and I. Stewart and H. Venning and L. Wedderburn and P. Woo and S. Wyatt and Angelo Ravelli and Rachelle Donn and Alberto Martini",
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TY - JOUR

T1 - Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis

AU - De Benedetti, Fabrizio

AU - Meazza, Cristina

AU - Vivarelli, Marina

AU - Rossi, Federica

AU - Pistorio, Angela

AU - Lamb, Rebecca

AU - Lunt, Mark

AU - Thomson, Wendy

AU - Abinun, M.

AU - Becker, M.

AU - Bell, A.

AU - Craft, A.

AU - Crawley, E.

AU - David, J.

AU - Foster, H.

AU - Gardener-Medwin, J.

AU - Griffin, J.

AU - Hall, A.

AU - Hall, M.

AU - Herrick, A.

AU - Hollingworth, P.

AU - Holt, L.

AU - Jones, S.

AU - Pountain, G.

AU - Ryder, C.

AU - Southwood, T.

AU - Stewart, I.

AU - Venning, H.

AU - Wedderburn, L.

AU - Woo, P.

AU - Wyatt, S.

AU - Ravelli, Angelo

AU - Donn, Rachelle

AU - Martini, Alberto

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Objective. To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods. A total of 136 patients with systemiconset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.

AB - Objective. To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods. A total of 136 patients with systemiconset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.

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