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AB0819 Tfh cells contribute to abnormal b cell profiles in dermatomyositis
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  1. X. Zhang,
  2. X. Ma,
  3. H. Wang,
  4. Z. Chen,
  5. L. Sun
  1. Department of Rheumatology And Immunology, THE AFFILIATED DRUM TOWER HOSPITAL, NANJING UNIVERSITY MEDICAL SCHOOL, NANJING, CHINA., Nanjing, China

Abstract

Background CD4 +CXCR5+PD-1+T follicular helper (Tfh) cells assist B cells in their proliferation, differentiation and antibody class switch(.1 Several studies indicate that Tfh cells play important roles in autoimmune diseases such as SLE, RA and pSS, which are characterised by the production of multiple antibodies(.2–4 The frequency of Tfh cells in the peripheral blood from patients with dermatomyositis(DM) and whether they participate in the development of DM remain to be elucidated.

Objectives To investigate the frequencies of Tfh cells and B cell profiles in DM patients. To further determine the association of Tfh cells and B cells in DM patients and clarify the possible mechanism.

Methods Peripheral blood mononuclear cells (PBMCs) were isolated from DM patients and age, gender-matched healthy controls (HCs), respectively. The frequency of Tfh (CD4 +CXCR5+PD-1+) cells, total B (CD19+) cells naïve B (CD19 +CD27-) cells, memory B(CD19 +CD27+) cells and plasmablasts (CD19 +CD38++) were examined by flow cytometry. The serum levels of IL-21, IgG, IgM, IgE and IgA were tested by enzyme linked immunosorbent assay (ELISA).

Results The percentages of circulating Tfh cells are significantly higher in DM patients than HCs (p<0.0001). Compared to HCs, the absolute numbers of circulating Tfh cells also upregulate markedly in DM patients(p<0.05). The mRNA expression levels of Bcl-6, a typical transcription factor of Tfh cells, increase apparently in PBMC from DM patients(p<0.05). Serum levels of IL-21, a Tfh-specific cytokine, are obviously higher in DM patients(p<0.01). The percentages of total B cells(p<0.01) and Naïve B cells(p<0.01) upregulate significantly in DM patients while Memory B cells(p<0.05) downregulate markedly when compared with HCs. The absolute numbers of plasmablasts(p<0.05) and Naïve B cells(p<0.05) increase notably while memory B cells decreased obviously(p<0.01). Serum levels of IgG(p<0.01), IgM(p<0.0001), IgE(p<0.01) and IgA(p<0.05) are obviously higher in DM patients(p<0.05). The frequencies of Tfh cells are positively correlated with total B cells (r=0.633, p<0.001) and Naïve B cells (r=0.643, p<0.01).

Conclusions Tfh cells may contribute to abnormal B cell profiles and antibodies production in DM and participate in the pathogenesis of DM. Tfh cell-targeted therapy might be a potential strategy for DM.

References [1] Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Forster R. 2000. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med192: 1545–52

[2] Le Coz C, Joublin A, Pasquali JL, Korganow AS, Dumortier H, Monneaux F. 2013. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease. PLoS One8: e75319

[3] Ma J, Zhu C, Ma B, Tian J, Baidoo SE, Mao C, Wu W, Chen J, Tong J, Yang M, Jiao Z, Xu H, Lu L, Wang S. 2012. Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis. Clin Dev Immunol2012: 827480

[4] Li XY, Wu ZB, Ding J, Zheng ZH, Li XY, Chen LN, Zhu P. 2012. Role of the frequency of blood CD4(+) CXCR5(+) CCR6(+) T cells in autoimmunity in patients with Sjogren’s syndrome. Biochem Biophys Res Commun422: 238–44

Acknowledgements None

Disclosure of Interest None declared

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