Advertisement

Neurological Sciences

, Volume 35, Issue 1, pp 29–34 | Cite as

Serum IL-21 levels decrease with glucocorticoid treatment in myasthenia gravis

  • Y. Li
  • V. K. Rauniyar
  • W. F. Yin
  • B. Hu
  • S. Ouyang
  • B. Xiao
  • H. Yang
Original Article

Abstract

This study aimed to observe the changes of IL-21/21R in peripheral blood of myasthenia gravis (MG) patients with glucocorticoid treatment and further clarify its role in pathogenesis of MG. 20 MG patients and 15 healthy controls were enrolled in this prospective study. Measurement of serum IL-21 concentration in healthy controls and MG patients before and after glucocorticoid treatment was done using ELISA, whereas expression of IL-21R mRNA was determined by RT-PCR. In addition, serum levels of specific anti-AChR-IgG and its subclasses IgG1, IgG2, IgG3 were also determined by ELISA as follows: (1) serum IL-21 concentration in MG patients was higher before treatment 86.94 ± 14.47 (pg/ml) and decreased significantly after glucocorticoid treatment 35.84 ± 16.13 (pg/ml) (p < 0.05), (2) relative OD values of IL-21R mRNA expressed in PBMCs of MG patients was higher 0.137 ± 0.023 and significantly decreased after glucocorticoid treatment 0.114 ± 0.023 (p < 0.05), while it was 0.107 ± 0.025 in control group, (3) serum concentration of IL-21 showed positive correlation with specific serum anti-AchR-IgG1 levels. The results indicate that the serum IL-21 decreases with glucocorticoid treatment and might be crucial in pathogenesis of mechanism of glucocorticoid treatment on MG patients.

Keywords

Myasthenia gravis Interleukin-21 Glucocorticoid treatment Anti-AchR antibody 

Notes

Acknowledgments

This work was supported by the National Nature Science Foundation of China (No. 81070962), MDA, and innovation project for postgraduate of central south university (No. 2010ssxt058).

References

  1. 1.
    Conti-Fine BM, Milani M, Kaminski HJ (2006) Myasthenia gravis: past, present, and future. J Clin Invest 116(11):2843–2854PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Conti-Fine BM, Milani M, Wang W (2008) CD4+ T cells and cytokines in the pathogenesis of acquired myasthenia gravis. Ann N Y Acad Sci 1132:193–209PubMedCrossRefGoogle Scholar
  3. 3.
    Parrish-Novak J, Dillon SR, Nelson A et al (2000) Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408:57–63PubMedCrossRefGoogle Scholar
  4. 4.
    Kim HP, Korn LL, Gamero AM et al (2005) Calcium-dependent activation of interleukin-21 gene expression in T cells. J Biol Chem 280:25291–25297PubMedCrossRefGoogle Scholar
  5. 5.
    Spolski R, Leonard WJ (2008) Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 26:57–79PubMedCrossRefGoogle Scholar
  6. 6.
    Ozaki K, Kikly K, Michalovich D et al (2000) Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci USA 97:11439–11444PubMedCrossRefGoogle Scholar
  7. 7.
    Liu R, Bai Y, Vollmer TL et al (2008) IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis. Exp Neurol 211:14–24PubMedCrossRefGoogle Scholar
  8. 8.
    Vollmer TL, Liu R, Price M et al (2005) Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen. J Immunol 174(5):2696–2701PubMedGoogle Scholar
  9. 9.
    Kasahara TM, Teixeira B, Ferreira TB et al (2013) The ex vivo production of IL-6 and IL-21 by CD4(+) T cells is directly associated with neurological disability in neuromyelitis optica patients. J Clin Immunol 33:179–189PubMedCrossRefGoogle Scholar
  10. 10.
    Hohlfeld R, Toyka KV, Heininger K (1984) Autoimmune human T lymphocyte specific for acetylcholine receptor. Nature 310:244–246PubMedCrossRefGoogle Scholar
  11. 11.
    Wang W, Milani M, Ostlie N et al (2007) C57BL/6 mice genetically deficient in IL-12/IL-23 and IFN-gamma are susceptible to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non-Th1 cells. J Immunol 178(11):7072–7080PubMedCentralPubMedGoogle Scholar
  12. 12.
    Yang H, Zhang Y, Wu M et al (2010) Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dendritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3 + regulatory T-cell profile. Inflamm Res 59(3):197–205PubMedCrossRefGoogle Scholar
  13. 13.
    Masuda M, Matsumoto M, Tanaka S et al (2010) Clinical implication of peripheral CD4+ CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients. J Neuroimmunol 225(1–2):123–131PubMedCrossRefGoogle Scholar
  14. 14.
    Hu B, Tian X, Huang H et al (2010) Expression of IL-21 in the peripheral blood of myasthenia gravis patients and its correlation with anti-AChR-Ab class switch. Zhong Nan Da Xue Xue Bao Yi Xue Ban 35(9):958–963 ChinesePubMedGoogle Scholar
  15. 15.
    Furukawa Y, Yoshikawa H, Iwasa K et al (2008) Clinical efficacy and cytokine network-modulating effects of tacrolimus in myasthenia gravis. J Neuroimmunol 195(1–2):108–115PubMedCrossRefGoogle Scholar
  16. 16.
    Spolski R, Leonard WJ (2008) The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer. Curr Opin Immunol 20(3):295–301PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ozaki K, Spolski R, Ettinger R et al (2004) Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol 173:5361–5371PubMedGoogle Scholar
  18. 18.
    Vinuesa CG, Cook MC, Angelucci C et al (2005) A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435:452–458PubMedCrossRefGoogle Scholar
  19. 19.
    Wang XF, Yuan SL, Jiang L et al (2007) Changes of serum BAFF and IL-21 levels in patients with systemic lupus erythematosus and their clinical significance. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 23(11):1041–1042 ChinesePubMedGoogle Scholar
  20. 20.
    Wong CK, Wong PT, Tam LS et al (2010) Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity. J Clin Immunol 30(1):45–52PubMedCrossRefGoogle Scholar
  21. 21.
    Rasmussen TK, Andersen T, Hvid M et al (2010) Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol 37(10):2014–2020PubMedCrossRefGoogle Scholar
  22. 22.
    Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8(5):475–490PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 335(1):2–13PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Spies CM, Gaber T, Hahne M et al (2010) Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells. Immunol Lett 131(1):24–32PubMedCrossRefGoogle Scholar
  25. 25.
    Stary G, Klein I, Bauer W et al (2011) Glucocorticosteroids modify Langerhans cells to produce TGF-β and expand regulatory T cells. J Immunol 186(1):103–112PubMedCrossRefGoogle Scholar
  26. 26.
    Momcilović M, Miljković Z, Popadić D et al (2008) Methylprednisolone inhibits interleukin-17 and interferon-gamma expression by both naive and primed T cells. BMC Immunol 9:47PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Jüngel A, Distler JH, Kurowska-Stolarska M et al (2004) Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis. Arthritis Rheum 50(5):1468–1476PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Y. Li
    • 1
  • V. K. Rauniyar
    • 1
    • 2
  • W. F. Yin
    • 1
  • B. Hu
    • 1
  • S. Ouyang
    • 1
    • 3
  • B. Xiao
    • 1
  • H. Yang
    • 1
  1. 1.Department of Neurology, Xiangya School of Medicine, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Medicine in Nobel Medical CollegeKathmandu UniversityBiratnagarNepal
  3. 3.Department of NeurologyThe First Hospital in Changsha CityChangshaPeople’s Republic of China

Personalised recommendations