FRI0058 Effect of mif gene haplotypes on rhtnf-a and rhmif response in peripheral blood mononuclear cells of rheumatoid arthritis patients
Authors: LA Hernandez-Palma, S Garcia-Arellano, S Cerpa-Cruz, JF Muñoz-Valle
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important role in the development and pathogenesis of rheumatoid arthritis (RA). MIF promotes the expression of cytokines related to RA development, as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-17. Two polymorphisms in the promoter of the <i>MIF</i> gene have been associated with increased production of protein and it has been shown that TNF-α is involved in the regulation of <i>MIF</i> mRNA expression and protein secretion in a dose-dependent manner. <h3>Objectives</h3> To evaluate the effect of <i>MIF</i> gene haplotypes on rhTNF-α and rhMIF response in peripheral blood mononuclear cells (PBMC) of RA patients <h3>Methods</h3> Genotyping was performed for <i>MIF</i> gene haplotypes in 230 RA patients. Cell culture of PBMC from two patients per homozygous haplotype (5G, 6G and 7C) was performed and stimulated with rhTNF-α and rhMIF. Cytokine levels were analyzed by a microsphere-based ELISA method (Bio-Plex® MAGPIX™). <h3>Results</h3> rhTNF-α and rhMIF-induced IL-6, IL-17A and IL-17F secretion in PBMC of RA patients. We observed that PBMC extracted from patients with MIF 7C haplotypes stimulated with rhTNF showed higher secretion of IL-17A and IL-17F than patients with 5G and 6G haplotypes. IL-6 production with rhMIF stimulation was more pronounced in the 5G haplotype group than 6G or 7C haplotype groups. <h3>Conclusions</h3> rhTNF-α and rhMIF promote differential secretion of IL-6, IL-17A and IL-17F according to <i>MIF</i> haplotypes presence. IL-17A and IL-17F secretion of stimulated PBMC with rhTNF-α are higher in patients with 7C haplotype than non-7C haplotypes. Furthermore, IL-6 levels are higher in PBMC from patients with 5G haplotype stimulated with MIF than non-5G haplotypes. <h3>References</h3> McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis - shaping the immunological landscape. Nat Rev Rheumatol 2016;12(1):63–68. Llamas-Covarrubias MA, Valle Y, Navarro-Hernández RE, Guzmán-Guzmán IP, Ramírez-Dueñas MG, Rangel-Villalobos H, Estrada-Chávez C, Muñoz-Valle JF. Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course. Rheumatol Int 2012;32(8):2307–2311. Stojanović I, Cvjetićanin T, Lazaroski S, Stosić-Grujicić S, Miljković D. Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells. Immunology. 2009;126(1):74–83. Gregersen PK y Bucala R. Macrophage migration inhibitory factor, MIF alleles, and the genetics of inflammatory disorders: incorporating disease outcome into the definition of phenotype. Arthritis Rheum. 2003;48(5):1171–6. Xiong C1, Huang B, Cun Y, Aghdasi BG, Zhou Y. Migration inhibitory factor enhances inflammation via CD74 in cartilage end plates with Modic type 1 changes on MRI. Clin Orthop Relat Res. 2014;472(6):1943–54. <h3>Acknowledgements</h3> This study was supported by funding from the National Council of Science and Technology (CONACYT) Grant #161749 assigned to JFMV. <h3>Disclosure of Interest</h3> None declared