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Evaluation of Expression of STAT Genes in Immune-Mediated Polyneuropathies


Immune-mediated polyneuropathies are acquired conditions that can be categorized to acute and chronic forms based on the disease course. Although the basic mechanism of these conditions has not been clarified yet, genes that regulate immune responses are putative contributors in their development. In the current study, we assessed expression of signal transducer and activator of transcription (STAT)1-3 and STAT5a genes in peripheral blood of 51 patients and 40 healthy subjects. Expression of STAT1 was higher in female patients compared with female controls (Posterior Beta = 3.622, P = 0.044). The gender*group interaction was significant for this gene which indicates different direction of association in males and females. Expressions of other STAT genes were not different between cases and controls. The diagnostic power of STAT1 in female subjects was estimated to be 0.72 with sensitivity of 68.75% and specificity of 84.62%. There was no significant correlation either between expression of different STAT genes or between their expression and age of study participants. The current study potentiates STAT1 as a putative factor in the pathophysiology of acquired immune-mediated polyneuropathies in females and suggests conduction of further functional studies to elaborate the molecular mechanism of this contribution.

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  1. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13:711–718

  2. Asbury AK, Cornblath DR (1990) Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol: Official Journal of the American Neurological Association and the Child Neurology Society 27:S21–S24

  3. Batten M, Li J, Yi S, Kljavin NM, Danilenko DM, Lucas S, Lee J, De Sauvage FJ, Ghilardi N (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 7:929–936

  4. Blanco LP, Plegue M, Fung-Leung WP, Holoshitz J (2013) Gender-biased regulation of human IL-17-producing cells in vitro by peptides corresponding to distinct HLA-DRB1 allele-coded sequences. J Immune Based Ther Vaccines Antimicrob 2:29–38

  5. Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O’Shea JJ (2006) Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A 103:8137–8142

  6. Chi LJ, Xu WH, Zhang ZW, Huang HT, Zhang LM, Zhou J (2010) Distribution of Th17 cells and Th1 cells in peripheral blood and cerebrospinal fluid in chronic inflammatory demyelinating polyradiculoneuropathy. J Peripher Nerv Syst 15:345–356

  7. Crncec I, Modak M, Gordziel C, Svinka J, Scharf I, Moritsch S, Pathria P, Schlederer M, Kenner L, Timelthaler G, Muller M, Strobl B, Casanova E, Bayer E, Mohr T, Stockl J, Friedrich K, Eferl R (2018) STAT1 is a sex-specific tumor suppressor in colitis-associated colorectal cancer. Mol Oncol 12:514–528

  8. Debnath M, Nagappa M, Murari G, TALY AB (2018) IL-23/IL-17 immune axis in Guillain Barre syndrome: exploring newer vistas for understanding pathobiology and therapeutic implications. Cytokine 103:77–82

  9. Eldar AH, Chapman J (2014) Guillain Barre syndrome and other immune mediated neuropathies: diagnosis and classification. Autoimmun Rev 13:525–530

  10. Gracey E, Yao Y, Green B, Qaiyum Z, Baglaenko Y, Lin A, Anton A, Ayearst R, Yip P, Inman RD (2016) Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis Rheumatol 68:679–689

  11. Hatami M, Salmani T, Arsang-Jang S, Davood Omrani M, Mazdeh M, Ghafouri-Fard S, Sayad A, Taheri M (2018) STAT5a and STAT6 gene expression levels in multiple sclerosis patients. Cytokine 106:108–113

  12. Hughes RA, Rees JH (1997) Clinical and epidemiologic features of Guillain-Barré syndrome. J Infect Dis 176:S92–S98

  13. Köller H, Kieseier BC, Jander S, Hartung H-P (2005) Chronic inflammatory demyelinating polyneuropathy. N Engl J Med 352:1343–1356

  14. Kun H, Cheng RF, Shan Zhou Y, Guo S, Dong H, He R, Jun Chi L, Ming Zhang L (2014) Increased circulating Th17 cell populations and elevated CSF osteopontin and IL-17 concentrations in patients with Guillain-Barre syndrome. J Clin Immunol 34:94–103

  15. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O’Shea J, J. (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371–381

  16. Manoochehrabadi S, Arsang-Jang S, Mazdeh M, Inoko H, Sayad A, Taheri M (2019) Analysis of STAT1, STAT2 and STAT3 mRNA expression levels in the blood of patients with multiple sclerosis. Hum Antibodies 27:91–98

  17. Momen AA, Shakurnia A (2017) The epidemiology of Guillain-Barré syndrome in children under 15 years old in Southwest Iran. Biomedicine Hub 2:1–8

  18. Neufert C, Becker C, Wirtz S, Fantini MC, Weigmann B, Galle PR, Neurath MF (2007) IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1. Eur J Immunol 37:1809–1816

  19. Nyati KK, Prasad KN (2014) Role of cytokines and toll-like receptors in the immunopathogenesis of Guillain-Barre syndrome. Mediat Inflamm 2014:758639

  20. Nyati KK, Prasad KN, Verma A, Singh AK, Rizwan A, Sinha S, Paliwal VK, Pradhan S (2010) Association of TLR4 Asp299Gly and Thr399Ile polymorphisms with Guillain-Barre syndrome in Northern Indian population. J Neuroimmunol 218:116–119

  21. O'Shea JJ, Steward-Tharp SM, Laurence A, Watford WT, Wei L, Adamson AS, Fan S (2009) Signal transduction and Th17 cell differentiation. Microbes Infect 11:599–611

  22. Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM (2016) Sex-based selectivity of PPARgamma regulation in Th1, Th2, and Th17 differentiation. Int J Mol Sci:17

  23. Peters A, Fowler KD, Chalmin F, Merkler D, Kuchroo VK, Pot C (2015) IL-27 induces Th17 differentiation in the absence of STAT1 signaling. J Immunol 195:4144–4153

  24. Saperstein DS, Amato AA, Wolfe GI, Katz JS, Nations SP, Jackson CE, Bryan WW, Burns DK, Barohn RJ (1999) Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis–Sumner syndrome. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine 22:560–566

  25. Schneider-Hohendorf T, Schwab N, Uceyler N, Gobel K, Sommer C, Wiendl H (2012) CD8+ T-cell immunity in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 78:402–408

  26. Sikorski K, Czerwoniec A, Bujnicki JM, Wesoly J, Bluyssen HA (2011) STAT1 as a novel therapeutical target in pro-atherogenic signal integration of IFNgamma, TLR4 and IL-6 in vascular disease. Cytokine Growth Factor Rev 22:211–219

  27. Villarino AV, Gallo E, Abbas AK (2010) STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms. J Immunol 185:6461–6471

  28. Yang XO, Panopoulos AD, Nurieva R, chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358–9363

  29. Young NA, Valiente GR, Hampton JM, Wu LC, Burd CJ, Willis WL, Bruss M, Steigelman H, Gotsatsenko M, Amici SA, Severin M, Claverie LM, Guerau-De-Arellano M, Lovett-Racke A, Ardoin S, Jarjour WN (2017) Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus. Clin Immunol 176:12–22

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The current study was supported by a grant from Shahid Beheshti University of Medical Sciences.

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Correspondence to Soudeh Ghafouri-Fard or Mohammad Mahdi Eftekharian.

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The study protocol was approved by the Ethical Committee of Shahid Beheshti University of Medical Sciences. All study participants signed the informed consent forms.

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The authors declare that they have no conflict of interest.

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Ali, Z.P.M., Taheri, M., Sangsefidi, S. et al. Evaluation of Expression of STAT Genes in Immune-Mediated Polyneuropathies. J Mol Neurosci (2020).

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  • Immune-mediated polyneuropathies
  • Signal transducer and activator of transcription
  • STAT