Sacide PEHLİVAN, Mazlum Serdar AKALTUN, Ali AYDENİZ, Savas GURSOY, Özlem ALTINDAĞ, Ali GUR, Tekin KARSLIGİL

The Relationship Between Cd 74 Levels, Macrophage Migration Inhibitory Factor Gene Polymorphism and Clinical Features in Patients with Ankylosing Spondylitis

Objective: In this study, the primary objective was to compare CD 74 antigen levels between patients with ankylosing spondylitis (AS) and healthy controls. The secondary objective was to investigate the distribution of Macrophage Migration Inhibitory Factor (MIF) 173 G/C polymorphisms in AS patients and a control group. Finally, it was also aimed to reveal the presence of a relationship between CD 74 antigen levels and MIF 173 G/C polymorphism. Materials and Methods: 82 healthy blood donors and 79 AS patients were enrolled in this study. MIF 173 G/C polymorphism and CD 74 levels were investigated in the patient and control groups using the ELISA method. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiology Index (BASRI), Visual Analogue Scale (VAS) and Ankylosing Spondylitis Quality of Life (ASQoL) scores were calculated and recorded. Results: There was no significant difference between the patient and control groups in terms of age, gender, and body mass index. The median CD74 level of the patient group was 1.17 (0.93-2.1), which was significantly lower than that of the control group, i.e. 2.16 (1.6-4.41). There was no correlation between CD 74 antigen levels and BASDAI, BASMI, BASFI, BASRI, VAS and ASQoL scores. The number of patients who had the C allele was higher among the patients with AS in comparison to the control group; however, the difference was not statistically significant (p>0.05). There was no correlation between genotypes and BASDAI, BASMI, BASFI, BASRI, VAS and ASQoL scores (p>0.05). Comparison of the median CD74 levels of the individuals in the patient group according to their HLA-B27 status and genotypes did not reveal any statistically significant difference. Conclusion: The CD74 antigen levels of the patients with AS were significantly lower compared to the control group. This implies that CD 74 is a parameter that can be used in the diagnosis of AS. Although the C allele among the MIF 173 G/C polymorphisms was more frequently observed in the patient group, the difference was not statistically significant. Moreover, there was no significant relationship between CD 74 antigen levels and polymorphisms.

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Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011;377(9783):2127-37.
Daikh DI, Chen PP. Advances in managing ankylosing spondylitis. F1000Prime Reports. 2014, 6:78.
Bandinelli, F., Salvadorini, G., Delle Sedie, A., Riente, L., Bombardieri, S., & Matucci-Cerinic, M. (2016). Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis. Clinical rheumatology, 35(2), 473-478.
Mercieca C, Landewe R, Borg AA. Spondylarthropathies Pathogenesis and Clinical Features. In: Bijlsma JWJ, Silva JAP, Hachulla E, Doherty M, Cope E, Liote F. Eular Textbook on Rheumatic Diseases. 1 st ed. London: BMJ Group, 2012; p 255-275)
Chen, B., Li, J., He, C., Li, D., Tong, W., Zou, Y., & Xu, W. (2017). Role of HLA-B27 in the pathogenesis of ankylosing spondylitis. Molecular medicine reports, 15(4), 1943-1951.
Davidson, S. I., Wu, X., Liu, Y., Wei, M., Danoy, P. A., Thomas, G. et al. (2009). Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 60(11), 3263-3268.
Brown, M.A., Genetics of ankylosing spondylitis. Current opinion in rheumatology, 2010. 22(2): p. 126-132
Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S et al. Autoantibodies against CD74 in spondyloarthritis. Annals of the rheumatic diseases, 2014, 73.6: 1211-1214
Schneppenheim J, Loock AC, Hüttl S, Schweizer M, Lüllmann-Rauch R, Oberg HH et al. The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments. J Immunol. 2017 Jul 1;199(1):172-185. doi: 10.4049/jimmunol.1601533
10. Kim, K. W., & Kim, H. R. (2016). Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis. The Korean journal of internal medicine, 31(4), 634.
11. Kasama T, Ohtsuka K, Sato M, Takahashi R, Wakabayashi K, Kobayashi K. “Macrophage migration inhibitory factor: a multifunctional cytokine in rheumatic diseases.” Arthritis 2010 (2011)
12. Santos, L., Hall, P., Metz, C., Bucala, R., & Morand, E. F. (2001). Role of macrophage migration inhibitory factor (MIF) in murine antigeninduced arthritis: interaction with glucocorticoids. Clinical & Experimental Immunology, 123(2), 309-314
13. Yang, J., Li, Y., & Zhang, X. (2015). Meta-analysis of macrophage migration inhibitory factor (MIF) gene-173G/C polymorphism and inf lammatory bowel disease (IBD) risk. International journal of clinical and experimental medicine, 8(6), 9570
14. Nishihira, J.,2012. Molecular fuction of macrophace migration factor and a novel therapy for inflammotory bowel disease. Ann NY Acad Sci., 1271:53-7
15. Bucala R, Shachar I (2014) The integral role of CD74 in antigen presentation, MIF signal transduction, and B cell survival and homeostasis. Mini Rev Med Chem 14(14):1132–1138
16. Brown, M. A., Kenna, T., & Wordsworth, B. P. (2016). Genetics of ankylosing spondylitis—insights into pathogenesis. Nature Reviews Rheumatology, 12(2), 81.
17. Bucala, R. 2013. MIF, MIF alleles, and prospects for therapeutic intervention in autoimmunity. J Clin Immunol., 33(1):72-8
18. Calandra, T., & Bucala, R. (2017). Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Critical Reviews™ in Immunology, 37(2-6).
19. Ohkawara T, Nishihira J, Takeda H, Hige S, Kato M, Sugiyama T et al. “Amelioration of dextran sulfate sodium–induced colitis by anti-macrophage migration inhibitory factor antibody in mice.” Gastroenterology 123.1 (2002): 256-270
20. Martínez A, Orozco G, Varadé J, Sánchez López M, Pascual D, Balsa A et al. “Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility,” Human Immunology, vol. 68, no. 9, pp. 744–747, 2007.
21. Radstake TR, Sweep FC, Welsing P, Franke B, Vermeulen SH, GeurtsMoespot A et al. “Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor.” Arthritis & Rheumatology52.10 (2005): 3020-3029.
22. Zheng X, Wang D, Hou S, Zhang C, Lei B, Xiao X et al. “Association of macrophage migration inhibitory factor gene polymorphisms with Behcet’s disease in a Han Chinese population.” Ophthalmology 119.12 (2012): 2514-2518
23. Przybyłowska K, Mrowicki J, Sygut A, Narbutt P, Dziki Ł, Dziki A et al. “Contribution of the-173 G/C polymorphism of macrophage migration inhibitory factor gene to the risk of inflammatory bowel diseases.” Polish Journal of Surgery 83.2 (2011): 76-80.
24. Gürel Ç, İnanır A, Nursal AF, Tekcan A, Rüstemoğlu A, Yigit S. “Evaluation of MIF-173 G/C Polymorphism in Turkish Patients with Ankylosing Spondylitis.” Balkan medical journal 33.6 (2016): 614.
25. Borghese F, Clanchy FI. CD74: an emerging opportunity as therapeutic target in cancer and autoimmune disease. Expert Opin Ther Targets. 2011;15:237–51
26. Su, H., Na, N., Zhang, X., & Zhao, Y. (2017). The biological function and significance of CD74 in immune diseases. Inflammation Research, 66(3), 209-216
27. Baraliakos X, Baerlecken N, Witte T, Heldmann F, Braun J. “High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis.” Annals of the rheumatic diseases (2013): annrheumdis-2012
28. Ranganathan V, Ciccia F, Zeng F, Sari I, Guggino G, Muralitharan J et al. “Macrophage Migration Inhibitory Factor induces inflammation and predicts spinal progression in Ankylosing Spondylitis.” Arthritis & Rheumatology (2017).