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Immunologic Research
Published in: Immunologic Research 5-6/2016

01-12-2016 | Original Article

CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients

Authors: Yong Zhang, Xiuying Zhang, Yan Xia, Xiao Jia, Hao Li, Yanyan Zhang, Zhen Shao, Ning Xin, Mingfeng Guo, Jing Chen, ShuangShuang Zheng, YuZhong Wang, Linlin Fu, Chenghua Xiao, Deqin Geng, Yonghai Liu, Guiyun Cui, Ruiguo Dong, Xiaoyu Huang, Tingyan Yu

Published in: Immunologic Research | Issue 5-6/2016

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Abstract

T cell immunoglobulin mucin domain-1(Tim-1) was recently identified to be critical and essential for optimal regulatory B cells function in maintaining immune tolerance. We aimed to measure the expression levels of Tim-1 on B cells from patients with Myasthenia Gravis (MG) and to investigate whether the expression of Tim-1 is associated with pathogenesis of MG. A total of 34 patients with MG (18 generalized MG (GMG) and 16 ocular MG (OMG) and 24 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and flow cytometry were used to measure the levels of Tim-1 expressed on peripheral B cells. Peripheral CD138+ plasma cells were assayed by flow cytometry. Serum Th17-related cytokines (IL-6, IL-1β and IL-17) and anti-AChR antibody (Ab) titers were tested by enzyme-linked immunosorbent assay (ELISA). Our data demonstrated that the mRNA and protein expression levels of B cell Tim-1 in both the GMG and OMG groups were significantly lower than those in healthy controls, with lower expression in GMG than in OMG. Tim-1 expression on B cells from OMG/GMG was negatively correlated with clinical severity, plasma cells frequency, serum Th17-related cytokines and anti-AChR Ab levels. Our results indicated that aberrant expression of Tim-1 exists on B cells and may contribute to the Th17 polarization and antibody-secreting plasma cells differentiation in MG patients.
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Literature
1.
Heldal AT, Owe JF, Gilhus NE, Romi F. Seropositive myasthenia gravis: a nationwide epidemiologic study. Neurology. 2009;73(2):150–1.CrossRefPubMed
2.
Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 1976;26(11):1054–9.CrossRefPubMed
3.
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry. 1985;48(12):1246–52.CrossRefPubMedPubMedCentral
4.
5.
6.
7.
DiLillo DJ, Matsushita T. Tedder TF.B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. Ann N Y Acad Sci. 2010;1183:38–57.CrossRefPubMed
8.
Umetsu SE, Lee WL, McIntire JJ, et al. TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol. 2005;6(5):447–54.CrossRefPubMed
9.
Xiao S, Zhu B, Jin H, et al. Tim-1 stimulation of dendritic cells regulates the balance between effector and regulatory T cells. Eur J Immunol. 2011;41(6):1539–49.CrossRefPubMedPubMedCentral
10.
Wong SH, Barlow JL, Nabarro S, Fallon PG, McKenzie AN. Tim-1 is induced on germinal centre B cells through B-cell receptor signalling but is not essential for the germinal centre response. Immunology. 2010;131:77–88.PubMedPubMedCentral
11.
Ding Q, Yeung M, Camirand G, et al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest. 2011;121:3645–56.CrossRefPubMedPubMedCentral
12.
Xiao S, Brooks CR, Sobel RA, Kuchroo VK. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. J Immunol. 2015;194(4):1602–8.CrossRefPubMedPubMedCentral
13.
Yeung MY, Ding Q, Brooks CR, et al. TIM-1 signaling is required for maintenance and induction of regulatory B cells. Am J Transpl. 2015;15(4):942–53.CrossRef
14.
15.
Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med. 1971;38:497–537.PubMed
16.
Sharshar T, Chevret S, Mazighi M, et al. Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis. J Neurol. 2000;247(4):286–90.CrossRefPubMed
17.
Yang H, Goluszko E, David C, et al. Mapping myasthenia gravis associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice. J Clin Invest. 2002;109:1111–20.CrossRefPubMedPubMedCentral
18.
Yoshikawa H, Satoh K, Yasukawa Y, Yamada M. Cytokine secretion by peripheral blood mononuclear cells in myasthenia gravis. J Clin Neurosci. 2002;9:133–6.CrossRefPubMed
19.
Daien C, Gailhac S, Mura T, et al. Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol. 2014;66(8):2037–46.CrossRefPubMed
20.
Heinemann K, Wilde B, Hoerning A, et al. Decreased IL-10+ regulatory B cells (Bregs) in lupus nephritis patients. Scand J Rheumatol. 2016;7:1–5 [Epub ahead of print].
21.
Knippenberg S, Peelen E, Smolders J. Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission. J Neuroimmunol. 2011;239(1–2):80–6.CrossRefPubMed
22.
Sun F, Ladha SS, Yang L, et al. Interleukin-10 producing-B cells and their association with responsiveness to rituximab in myasthenia gravis. Muscle Nerve. 2014;49(4):487–94.CrossRefPubMed
23.
Xiao S, Brooks CR, Zhu C, et al. Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice. Proc Natl Acad Sci USA. 2012;109(30):12105–10.CrossRefPubMedPubMedCentral
24.
Gray M, Miles K, Salter D, Gray D, Savill J. Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci USA. 2007;104(35):14080–5.CrossRefPubMedPubMedCentral
25.
Miles K, Heaney J, Sibinska Z, et al. A tolerogenic role for Toll-like receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells. Proc Natl Acad Sci USA. 2010;109(3):887–92.CrossRef
26.
Mu L, Sun B, Kong Q, et al. Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during the development of experimental autoimmune myasthenia gravis. Immunology. 2009;128(1 Suppl):e826–36.CrossRefPubMedPubMedCentral
27.
Aricha R, Mizrachi K, Fuchs S, Souroujon MC. Blocking of IL-6 suppresses experimental autoimmune myasthenia gravis. J Autoimmun. 2011;36(2):135–41.CrossRefPubMed
28.
Alahgholi-Hajibehzad M, Oflazer P, Aysal F, et al. Regulatory function of CD4+ CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity. J Neuroimmunol. 2015;281:51–60.CrossRefPubMed
29.
30.
Doreau A, Belot A, Bastid J, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10(7):778–85.CrossRefPubMed
31.
Schaffert H, Pelz A, Saxena A, et al. IL-17-producing CD4(+) T cells contribute to the loss of B-cell tolerance in experimental autoimmune myasthenia gravis. Eur J Immunol. 2015;45(5):1339–47.CrossRefPubMed
32.
Hoffman W, Lakkis FG, Chalasani G. B cells, antibodies, and More. Clin J Am Soc Nephrol. 2016;11(1):137–54.CrossRefPubMed
33.
Li Z, Ju Z, Frieri M. The T-cell immunoglobulin and mucin domain (Tim) gene family in asthma, allergy, and autoimmunity. Allergy Asthma Proc. 2013;34(1):e21–6.CrossRefPubMed
34.
de Souza AJ, Oriss TB, O’malley KJ, Ray A, Kane LP. T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and provides a costimulatory signal for T cell activation. Proc Natl Acad Sci USA. 2005;102(47):17113–8.CrossRefPubMedPubMedCentral
35.
Yang H, Zhang Y, Wu M, Li J, Zhou W, Li G, Li X, Xiao B, Christadoss P. Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile. Inflamm Res. 2010;59(3):197–205.CrossRefPubMed
Metadata
Title
CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients
Authors
Yong Zhang
Xiuying Zhang
Yan Xia
Xiao Jia
Hao Li
Yanyan Zhang
Zhen Shao
Ning Xin
Mingfeng Guo
Jing Chen
ShuangShuang Zheng
YuZhong Wang
Linlin Fu
Chenghua Xiao
Deqin Geng
Yonghai Liu
Guiyun Cui
Ruiguo Dong
Xiaoyu Huang
Tingyan Yu
Publication date
01-12-2016
Publisher
Springer US
Published in
Immunologic Research / Issue 5-6/2016
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-016-8872-0

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