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Published in: Neurological Sciences 7/2017

01-07-2017 | Original Article

Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders

Authors: Jinming Han, Li Sun, Zhongkun Wang, Xueli Fan, Lifang Wang, Yang-yang Song, Jie Zhu, Tao Jin

Published in: Neurological Sciences | Issue 7/2017

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Abstract

This study analyzed the populations of three different subsets of regulatory B cells (Bregs) in the peripheral blood mononuclear cells (PBMCs) of patients with neuromyelitis optica spectrum disorders (NMOSDs) and explored the relationship between the changes in these subsets of Bregs and the severity of NMOSD. A total of 22 patients with relapsed NMOSDs before treatment were recruited in our study, along with 20 age and gender-matched healthy controls, from May 2015 to March 2016. The percentages and numbers for three different subsets of Bregs including the CD19+CD24hiCD38hi, CD19+CD24hiCD27+, and CD19+CD5+CD1dhi populations were evaluated in parallel by flow cytometry. Afterwards, correlations between the change of three different subsets of Bregs and disease severity were analyzed. We found significantly lower percentages of CD19+CD24hiCD38hi and CD19+CD5+CD1dhi Bregs in NMOSDs patients than in healthy individuals. In contrast, the CD19+CD24hiCD27+ Bregs population was significantly higher in NMOSDs patients than in healthy individuals. However, the three different Bregs subsets showed no significant correlation with expanded disability status scale (EDSS) or annualized relapse rate (ARR). Our findings suggest that the subsets of Bregs may play complex roles in the pathogenesis of NMOSDs and are not correlated with clinical disease severity. Further insights into the potential role of subsets of Bregs could increase our basic knowledge of NMOSDs pathogenesis.
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Literature
1.
go back to reference Jasiak-Zatonska M, Kalinowska-Lyszczarz A, Michalak S, Kozubski W (2016) The immunology of neuromyelitis optica—current knowledge, clinical implications, controversies and future perspectives. Int J Mol Sci 17(3):273CrossRefPubMedPubMedCentral Jasiak-Zatonska M, Kalinowska-Lyszczarz A, Michalak S, Kozubski W (2016) The immunology of neuromyelitis optica—current knowledge, clinical implications, controversies and future perspectives. Int J Mol Sci 17(3):273CrossRefPubMedPubMedCentral
2.
go back to reference Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (2015) N.M.O.D. International panel for, International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189CrossRefPubMedPubMedCentral Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (2015) N.M.O.D. International panel for, International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189CrossRefPubMedPubMedCentral
3.
go back to reference Krumbholz M, Meinl E (2014) B cells in MS and NMO: pathogenesis and therapy. Semin Immunopathol 36(3):339–350CrossRefPubMed Krumbholz M, Meinl E (2014) B cells in MS and NMO: pathogenesis and therapy. Semin Immunopathol 36(3):339–350CrossRefPubMed
4.
go back to reference Bennett JL, O’Connor KC, Bar-Or A, Zamvil SS, Hemmer B, Tedder TF, von Budingen HC, Stuve O, Yeaman MR, Smith TJ, Stadelmann C (2015) B lymphocytes in neuromyelitis optica. Neurology(R) neuroimmunology & neuroinflammation 2(3):e104CrossRef Bennett JL, O’Connor KC, Bar-Or A, Zamvil SS, Hemmer B, Tedder TF, von Budingen HC, Stuve O, Yeaman MR, Smith TJ, Stadelmann C (2015) B lymphocytes in neuromyelitis optica. Neurology(R) neuroimmunology & neuroinflammation 2(3):e104CrossRef
5.
go back to reference Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112CrossRefPubMed Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112CrossRefPubMed
6.
go back to reference Egwuagu CE, Yu CR (2015) Interleukin 35-producing B cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57CrossRefPubMedPubMedCentral Egwuagu CE, Yu CR (2015) Interleukin 35-producing B cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57CrossRefPubMedPubMedCentral
7.
8.
go back to reference Lee KM, Stott RT, Zhao G, SooHoo J, Xiong W, Lian MM, Fitzgerald L, Shi S, Akrawi E, Lei J, Deng S, Yeh H, Markmann JF, Kim JI (2014) TGF-beta-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol 44(6):1728–1736CrossRefPubMedPubMedCentral Lee KM, Stott RT, Zhao G, SooHoo J, Xiong W, Lian MM, Fitzgerald L, Shi S, Akrawi E, Lei J, Deng S, Yeh H, Markmann JF, Kim JI (2014) TGF-beta-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol 44(6):1728–1736CrossRefPubMedPubMedCentral
9.
10.
go back to reference Correale J, Farez M, Razzitte G (2008) Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64(2):187–199CrossRefPubMed Correale J, Farez M, Razzitte G (2008) Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64(2):187–199CrossRefPubMed
11.
go back to reference Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32(1):129–140CrossRefPubMed Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32(1):129–140CrossRefPubMed
12.
go back to reference Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, Clair EWS, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541CrossRefPubMedPubMedCentral Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, Clair EWS, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541CrossRefPubMedPubMedCentral
13.
go back to reference de Andres C, Tejera-Alhambra M, Alonso B, Valor L, Teijeiro R, Ramos-Medina R, Mateos D, Faure F, Sanchez-Ramon S (2014) New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. J Neuroimmunol 270(1–2):37–44CrossRefPubMed de Andres C, Tejera-Alhambra M, Alonso B, Valor L, Teijeiro R, Ramos-Medina R, Mateos D, Faure F, Sanchez-Ramon S (2014) New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. J Neuroimmunol 270(1–2):37–44CrossRefPubMed
14.
go back to reference Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert JW, Hupperts R, Damoiseaux J (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naive/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239(1–2):80–86CrossRefPubMed Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert JW, Hupperts R, Damoiseaux J (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naive/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239(1–2):80–86CrossRefPubMed
15.
go back to reference Michel L, Chesneau M, Manceau P, Genty A, Garcia A, Salou M, Elong Ngono A, Pallier A, Jacq-Foucher M, Lefrere F, Wiertlewski S, Soulillou JP, Degauque N, Laplaud DA, Brouard S (2014) Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol 155(2):198–208CrossRefPubMed Michel L, Chesneau M, Manceau P, Genty A, Garcia A, Salou M, Elong Ngono A, Pallier A, Jacq-Foucher M, Lefrere F, Wiertlewski S, Soulillou JP, Degauque N, Laplaud DA, Brouard S (2014) Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol 155(2):198–208CrossRefPubMed
16.
go back to reference Quan C, Yu H, Qiao J, Xiao B, Zhao G, Wu Z, Li Z, Lu C (2013) Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis. Mult Scler 19(3):289–298CrossRefPubMed Quan C, Yu H, Qiao J, Xiao B, Zhao G, Wu Z, Li Z, Lu C (2013) Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis. Mult Scler 19(3):289–298CrossRefPubMed
17.
go back to reference Yang F, Huang D, Cheng C, Wu W (2015) Proportion and significance of CD1d(hi)CD5(+)CD19(+) regulatory B cell in peripheral blood of patients with neuromyelitis optica. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 31(3):375–378PubMed Yang F, Huang D, Cheng C, Wu W (2015) Proportion and significance of CD1d(hi)CD5(+)CD19(+) regulatory B cell in peripheral blood of patients with neuromyelitis optica. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 31(3):375–378PubMed
18.
go back to reference Zha B, Wang L, Liu X, Liu J, Chen Z, Xu J, Sheng L, Li Y, Chu Y (2012) Decrease in proportion of CD19+ CD24(hi) CD27+ B cells and impairment of their suppressive function in Graves’ disease. PLoS One 7(11):e49835CrossRefPubMedPubMedCentral Zha B, Wang L, Liu X, Liu J, Chen Z, Xu J, Sheng L, Li Y, Chu Y (2012) Decrease in proportion of CD19+ CD24(hi) CD27+ B cells and impairment of their suppressive function in Graves’ disease. PLoS One 7(11):e49835CrossRefPubMedPubMedCentral
19.
go back to reference Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504CrossRefPubMed Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504CrossRefPubMed
20.
go back to reference Daien CI, Gailhac S, Mura T, Audo R, Combe B, Hahne M, Morel J (2014) Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol 66(8):2037–2046CrossRefPubMed Daien CI, Gailhac S, Mura T, Audo R, Combe B, Hahne M, Morel J (2014) Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol 66(8):2037–2046CrossRefPubMed
21.
go back to reference Todd SK, Pepper RJ, Draibe J, Tanna A, Pusey CD, Mauri C, Salama AD (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 53(9):1693–1703CrossRefPubMedPubMedCentral Todd SK, Pepper RJ, Draibe J, Tanna A, Pusey CD, Mauri C, Salama AD (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 53(9):1693–1703CrossRefPubMedPubMedCentral
22.
go back to reference Barsotti NS, Almeida RR, Costa PR, Barros MT, Kalil J, Kokron CM (2016) IL-10-producing regulatory B cells are decreased in patients with common variable immunodeficiency. PLoS One 11(3):e0151761CrossRefPubMedPubMedCentral Barsotti NS, Almeida RR, Costa PR, Barros MT, Kalil J, Kokron CM (2016) IL-10-producing regulatory B cells are decreased in patients with common variable immunodeficiency. PLoS One 11(3):e0151761CrossRefPubMedPubMedCentral
Metadata
Title
Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders
Authors
Jinming Han
Li Sun
Zhongkun Wang
Xueli Fan
Lifang Wang
Yang-yang Song
Jie Zhu
Tao Jin
Publication date
01-07-2017
Publisher
Springer Milan
Published in
Neurological Sciences / Issue 7/2017
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-017-2932-7

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