Delivery of an MiR155 Inhibitor by Anti-CD20 Single-chain Antibody into B Cells Reduces the Acetylcholine Receptor-specific Autoantibodies and Ameliorates Experimental Autoimmune Myasthenia Gravis

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2014 Jan 7

PMID 24387321

Citations 19

Authors

Y-Z Wang

F-F Tian

M Yan

J-M Zhang

Q Liu

J-Y Lu

W-B Zhou

H Yang

J Li

Affiliations

Soon will be listed here.

Abstract

MicroRNA-155 (miR155) is required for antibody production after vaccination with attenuated Salmonella. miR155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin (Ig)G1 antibodies. In this study, we observed up-regulation of miR155 in the peripheral blood mononuclear cells (PBMCs) of patients with myasthenia gravis (MG), and miR155 was also up-regulated in torpedo acetylcholine receptor (T-AChR)-stimulated B cells. We used an inhibitor of miR155 conjugated to anti-CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG (EAMG) mice. Our results demonstrated that silencing of miR155 by its inhibitor impaired the B cell-activating factor (BAFF)-R-related signalling pathway and reduced the translocation of nuclear factor (NF)-κB into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that miR155 may be a promising target for the clinical therapy of MG.

Citing Articles

The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment.

Wang B, Zhu Y, Liu D, Hu C, Zhu R Front Immunol. 2024; 15:1342213.

PMID: 38605954 PMC: 11007667. DOI: 10.3389/fimmu.2024.1342213.

MicroRNA‑155‑5p affects regulatory T cell activation and immunosuppressive function by targeting BCL10 in myasthenia gravis.

Sun J, Sun M, Li X, Xie Q, Zhang W, Wang M Exp Ther Med. 2024; 27(1):6.

PMID: 38223327 PMC: 10785013. DOI: 10.3892/etm.2023.12293.

miRNAs as the important regulators of myasthenia gravis: involvement of major cytokines and immune cells.

Golabi M, Yousefi Z, Jafarinia M, Montazeri M, Bastan S, Ghezelbash B Immunol Res. 2022; 71(2):153-163.

PMID: 36396903 DOI: 10.1007/s12026-022-09342-4.

MicroRNAs, Stem Cells in Bipolar Disorder, and Lithium Therapeutic Approach.

Coradduzza D, Garroni G, Congiargiu A, Balzano F, Cruciani S, Sedda S Int J Mol Sci. 2022; 23(18).

PMID: 36142403 PMC: 9502703. DOI: 10.3390/ijms231810489.

Myasthenia Gravis: An Acquired Interferonopathy?.

Payet C, You A, Fayet O, Dragin N, Berrih-Aknin S, Le Panse R Cells. 2022; 11(7).

PMID: 35406782 PMC: 8997999. DOI: 10.3390/cells11071218.

References

Vigorito E, Perks K, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S . microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity. 2007; 27(6):847-59. PMC: 4135426. DOI: 10.1016/j.immuni.2007.10.009. View

Li P, Liu D, Liu Y, Song S, Wang Q, Chang Y . BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin. J Ethnopharmacol. 2012; 141(1):290-300. DOI: 10.1016/j.jep.2012.02.034. View

Thai T, Calado D, Casola S, Ansel K, Xiao C, Xue Y . Regulation of the germinal center response by microRNA-155. Science. 2007; 316(5824):604-8. DOI: 10.1126/science.1141229. View

Suvas S, Singh V, Sahdev S, Vohra H, Agrewala J . Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. J Biol Chem. 2001; 277(10):7766-75. DOI: 10.1074/jbc.M105902200. View

Kurowska-Stolarska M, Alivernini S, Ballantine L, Asquith D, Millar N, Gilchrist D . MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011; 108(27):11193-8. PMC: 3131377. DOI: 10.1073/pnas.1019536108. View

Schiemann B, Gommerman J, Vora K, Cachero T, Dobles M, Frew E . An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001; 293(5537):2111-4. DOI: 10.1126/science.1061964. View

Jurgensmeier J, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed J . Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A. 1998; 95(9):4997-5002. PMC: 20202. DOI: 10.1073/pnas.95.9.4997. View

Cragg M, Walshe C, Ivanov A, Glennie M . The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2004; 8:140-74. DOI: 10.1159/000082102. View

Marton S, Garcia M, Robello C, Persson H, Trajtenberg F, Pritsch O . Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia. 2007; 22(2):330-8. DOI: 10.1038/sj.leu.2405022. View

10.

Taganov K, Boldin M, Chang K, Baltimore D . NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006; 103(33):12481-6. PMC: 1567904. DOI: 10.1073/pnas.0605298103. View

11.

Kim Y, Choi B, Cheon H, Do M . B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation. Exp Mol Med. 2009; 41(3):208-16. PMC: 2679246. DOI: 10.3858/emm.2009.41.3.024. View

12.

BERMAN P, Patrick J . Experimental myasthenia gravis. A murine system. J Exp Med. 1980; 151(1):204-23. PMC: 2185769. DOI: 10.1084/jem.151.1.204. View

13.

Hendricks J, Visser A, Dammers P, Burgerhof J, Bos N, Kroese F . Class-switched marginal zone B cells in spleen have relatively low numbers of somatic mutations. Mol Immunol. 2011; 48(6-7):874-82. DOI: 10.1016/j.molimm.2010.12.020. View

14.

Gross J, Dillon S, Mudri S, Johnston J, Littau A, Roque R . TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity. 2001; 15(2):289-302. DOI: 10.1016/s1074-7613(01)00183-2. View

15.

Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A . Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001; 7(3):365-8. DOI: 10.1038/85520. View

16.

Macpherson G, Kushnir N, Wykes M . Dendritic cells, B cells and the regulation of antibody synthesis. Immunol Rev. 2000; 172:325-34. DOI: 10.1111/j.1600-065x.1999.tb01376.x. View

17.

Maloney D, Liles T, Czerwinski D, Waldichuk C, Rosenberg J, Grillo-Lopez A . Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994; 84(8):2457-66. View

18.

Jaretzki 3rd A, Barohn R, Ernstoff R, Kaminski H, KEESEY J, Penn A . Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000; 55(1):16-23. DOI: 10.1212/wnl.55.1.16. View

19.

Martin F, Kearney J . Marginal-zone B cells. Nat Rev Immunol. 2002; 2(5):323-35. DOI: 10.1038/nri799. View

20.

Gironella M, Seux M, Xie M, Cano C, Tomasini R, Gommeaux J . Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A. 2007; 104(41):16170-5. PMC: 2042180. DOI: 10.1073/pnas.0703942104. View