CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients.
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.
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. zy20037416@163.com.
Yong
Y
Zhang
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.|Department of Neurology, Shenzhen Guangming New District Central Hospital, Shenzhen, China.
Xiuying
X
Zhang
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yan
Y
Xia
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xiao
X
Jia
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Hao
H
Li
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.|Department of Neurology, The Third People's Hospital of Xuzhou, Xuzhou, Jiangsu, China.
Yanyan
Y
Zhang
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Zhen
Z
Shao
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Ning
N
Xin
Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
Mingfeng
M
Guo
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Jing
J
Chen
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
ShuangShuang
S
Zheng
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
YuZhong
Y
Wang
Department of Pathogenic Biology and Lab of Infection and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
Linlin
L
Fu
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. chenghuaxiaoxzbj@163.com.
Chenghua
C
Xiao
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Deqin
D
Geng
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yonghai
Y
Liu
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Guiyun
G
Cui
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Ruiguo
R
Dong
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xiaoyu
X
Huang
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Tingyan
T
Yu
D000328:Adult; D000906:Antibodies / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
D000906:Antibodies; D018941:Antigens, CD19; D016207:Cytokines; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D011950:Receptors, Cholinergic
B cells; Disease severity; Myasthenia gravis; Tim-1
Scand J Rheumatol. 2016 Jul;45(4):312-6
26948375
J Clin Invest. 2011 Sep;121(9):3645-56
21821911
Inflamm Res. 2010 Mar;59(3):197-205
19768385
Eur J Immunol. 2011 Jun;41(6):1539-49
21469101
Neurology. 2009 Jul 14;73(2):150-1
19597135
Nat Rev Nephrol. 2012 Sep;8(9):505-14
22801948
Immunology. 2010 Sep;131(1):77-88
20518819
J Immunol. 2015 Feb 15;194(4):1602-8
25582854
J Neurol. 2000 Apr;247(4):286-90
10836621
Arthritis Rheumatol. 2014 Aug;66(8):2037-46
24729478
Nat Immunol. 2005 May;6(5):447-54
15793575
J Clin Invest. 2002 Apr;109(8):1111-20
11956249
Mt Sinai J Med. 1971 Nov-Dec;38(6):497-537
4941403
J Neurosci Res. 2016 Aug;94(8):693-701
27112131
Am J Transplant. 2015 Apr;15(4):942-53
25645598
Nat Immunol. 2009 Jul;10 (7):778-85
19483719
J Clin Neurosci. 2002 Mar;9(2):133-6
11922699
Annu Rev Immunol. 2009;27:485-517
19132915
J Neuroimmunol. 2011 Oct 28;239(1-2):80-6
21940055
J Autoimmun. 2011 Mar;36(2):135-41
21193288
Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):887-92
22207622
N Engl J Med. 2009 Jun 18;360(25):2683-5
19535812
Ann N Y Acad Sci. 2010 Jan;1183:38-57
20146707
J Neuroimmunol. 2015 Apr 15;281:51-60
25867468
Clin J Am Soc Nephrol. 2016 Jan 7;11(1):137-54
26700440
Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14080-5
17715067
Allergy Asthma Proc. 2013 Jan-Feb;34(1):e21-6
23406933
Immunology. 2009 Sep;128(1 Suppl):e826-36
19740344
Muscle Nerve. 2014 Apr;49(4):487-94
23868194
N Engl J Med. 1994 Jun 23;330(25):1797-810
8190158
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17113-8
16284246
Neurology. 1976 Nov;26(11):1054-9
988512
Eur J Immunol. 2015 May;45(5):1339-47
25676041
J Neurol Neurosurg Psychiatry. 1985 Dec;48(12):1246-52
4087000
Proc Natl Acad Sci U S A. 2012 Jul 24;109 (30):12105-10
22773818