ORIGINAL ARTICLE Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile Christian Johana Baños-Hernández 1,2 & José Eduardo Navarro-Zarza 3 & Richard Bucala 4 & Jorge Hernández-Bello 1,5 & Isela Parra-Rojas 2 & María Guadalupe Ramírez-Dueñas 6 & Samuel García-Arellano 1,5 & Luis Alexis Hernández-Palma 1 & Andrea Carolina Machado-Sulbarán 6 & José Francisco Muñoz-Valle 1,5 Received: 7 November 2018 /Revised: 12 January 2019 /Accepted: 28 January 2019 # International League of Associations for Rheumatology (ILAR) 2019 Abstract Introduction Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms - 794 CATT 5–8 (rs5844572) and - 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the - 794 CATT 5–8 and - 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. Materials and methods A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. Results An association between the - 794 CATT 7 and - 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p= 0.03) in SSc. In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles. Conclusion The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc. Keywords Cytokine profiles Th1/Th2/Th17 . MIF . MIF mRNA expression . Promoter polymorphisms . Systemic sclerosis Introduction Systemic sclerosis (SSc), also referred to as scleroderma, is an autoimmune disease characterized by three pathological process- es: microvascular lesions, impaired immune response, and fibro- sis in skin and internal organs [1]. The heterogeneity of the clin- ical characteristics in SSc allows classifying patients based on their skin condition in limited cutaneous (lcSSc) and diffuse cu- taneous SSc (dcSSc), the latter with worse prognosis [2]. Although SSc is a rare disease, it has one of the highest mortality rates among rheumatic diseases [3]. The etiology of SSc remains unknown, but it has been as- sociated with several risk factors such as genetic and * José Francisco Muñoz-Valle biologiamolecular@hotmail.com 1 Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico 2 Doctorado en Ciencias Biomédicas, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo de los Bravo, Guerrero, Mexico 3 Departamento de Medicina Interna-Reumatología, Hospital General de Chilpancingo BDr. Raymundo Abarca Alarcón^, Chilpancingo de los Bravo, Guerrero, Mexico 4 Department of Medicine/Section of Rheumatology, Yale University School of Medicine, New Haven, CT, USA 5 Instituto Transdisciplinar de Investigación y Servicios, Universidad de Guadalajara, Zapopan, Jalisco, Mexico 6 Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico Clinical Rheumatology https://doi.org/10.1007/s10067-019-04459-8