Association of Circulating Follicular Helper T Cells and Serum CXCL13 With Neuromyelitis Optica Spectrum Disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory diseases mediated mainly by humoral and cellular immunity. Circulating follicular helper T (Tfh) cells are thought to be involved in the pathogenesis of NMOSD, and serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of Tfh cells on B-cell-mediated humoral immunity. Immune cell and cytokine changes during the dynamic relapsing and remitting processes in NMOSD require further exploration.Patients and methodsBlood samples were collected from 36 patients in acute and recovery phases of NMOSD, 20 patients with other noninflammatory neurological diseases (ONND) and 20 age- and sex-matched healthy volunteers. CD4+CXCR5+PD-1+ Tfh cells were detected by flow cytometry, and serum CXCL13 levels were assessed by enzyme-linked immunosorbent assay (ELISA).ResultsThe percentage of CD4+CXCR5+PD-1+ Tfh cells was significantly higher during the acute phase than during the recovery phase, and serum CXCL13 levels were significantly higher in patients in the acute and recovery phases of NMOSD than in the ONND and control groups. The Tfh cell percentage was positively correlated with CXCL13 levels, and both were positively correlated with Expanded Disability Status Scale (EDSS) scores and cerebrospinal fluid protein levels in patients with acute NMOSD.ConclusionCirculating Tfh cells level has the potential to be a biomarker of disease severity.

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Circulating Memory T Follicular Helper Cells in Patients with Neuromyelitis Optica/Neuromyelitis Optica Spectrum Disorders

Mediators of Inflammation ◽

10.1155/2016/3678152 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 13

Author(s):

Xueli Fan ◽

Yanfang Jiang ◽

Jinming Han ◽

Jingyao Liu ◽

Yafen Wei ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Potential Role ◽

Neuromyelitis Optica Spectrum Disorders ◽

Tfh Cells ◽

Follicular Helper ◽

Cell Counts ◽

Before And After ◽

Spectrum Disorders ◽

White Blood Cell Counts

Objective. This study aimed to examine the potential role of memory T follicular helper (Tfh) cells in patients with neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD).Methods. The percentages of different subsets of circulating memory Tfh cells in 25 NMO/NMOSD patients before and after treatment as well as in 17 healthy controls were examined by flow cytometry. The levels of IL-21 and AQP4 Ab in plasma and CSF were measured by ELISA.Results. The percentages and numbers of circulating memory Tfh cells, ICOS+, CCR7−, CCR7−ICOS+, CCR7+, CCR7+ICOS+memory Tfh cells, and the levels of IL-21 in plasma and CSF were significantly increased in NMO/NMOSD patients. The percentages of CCR7−and CCR7−ICOS+memory Tfh cells were positively correlated with ARR, plasma IL-21, and AQP4 Ab levels. The percentages of CCR7+and CCR7+ICOS+memory Tfh cells were positively correlated with CSF white blood cell counts, proteins, and IL-21 levels. Treatment with corticosteroids significantly reduced the numbers of CCR7−ICOS+and CCR7+ICOS+memory Tfh cells as well as plasma IL-21 levels in patients with partial remission.Conclusions. Our findings indicate that circulating memory Tfh cells may participate in the relapse and development of NMO/NMOSD and may serve as a new therapeutic target.

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Association of Circulating T Follicular Helper Cells With Idiopathic Optic Neuritis and Neuromyelitis Optica Spectrum Disorders

Frontiers in Neurology ◽

10.3389/fneur.2021.638473 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qian Wu ◽

Binbin Yang ◽

Jiawei Wang

Keyword(s):

Optic Neuritis ◽

Neuromyelitis Optica ◽

Healthy Controls ◽

Neuromyelitis Optica Spectrum Disorders ◽

T Follicular Helper Cells ◽

Tfh Cells ◽

Helper Cells ◽

Follicular Helper ◽

Significant Difference ◽

Spectrum Disorders

Background: T follicular helper cells (Tfh cells) play an important role in activating B lymphocytes and may associate with idiopathic Optic Neuritis (ON) and Neuromyelitis Optica Spectrum Disorders (NMOSD).Objective: This study aimed to examine the potential role of Tfh cells in pathogenesis of idiopathic ON and NMOSD.Methods: Circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+ cells in 46 idiopathic ON and 68 NMOSD patients as well as 28 healthy controls were examined by flow cytometry before treatment. Serum AQP4 antibody, Expended Disability Status Scale (EDSS) and Visual Outcome Scale (VOS) were detected before and after treatment.Results: The percentages of circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+Tfh cells in CD4+ cells (%) were significantly increased in idiopathic ON and NMOSD compared with those of healthy controls (p < 0.01). No significant difference of Tfh cells in blood and cerebral spinal fluid (CSF) was found between ON and NMOSD patients. The percentages of CSF, CD4+, CXCR5+, and CD4+CXCR5+PD-1+ cells in CD4+ cells (%) were positively correlated with those of the blood (r = 0.5781, r = 0.6079, p = 0.0076, and p = 0.0045, respectively). EDSS scores of NMOSD group were higher than those of ON group and the time course of NMOSD patients was longer than that of ON patients (p < 0.01). After methylprednisolone treatment, both EDSS and VOS scores were significantly decreased at discharge compared with before treatment (p < 0.01). There was no significant correlation among Tfh cell percentages in CD4+ cells, CSF leukocytes, CSF protein, annual recurrence rate, EDSS and VOS scores between two groups (p > 0.05).Conclusion: The Circulating T follicular helper cells were increased in both idiopathic ON and NMOSD.

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Neuromyelitis Optica Spectrum Disorders

Neuroimmunology ◽

10.1093/med/9780190050801.003.0006 ◽

2019 ◽

pp. 109-129

Author(s):

A. Sebastian López-Chiriboga ◽

Brian G. Weinshenker

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Neuromyelitis Optica ◽

Inflammatory Diseases ◽

Treatment Options ◽

Neuromyelitis Optica Spectrum Disorders ◽

Future Prospects ◽

Mortality And Morbidity ◽

The Central Nervous System ◽

Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory diseases of the central nervous system, traditionally diagnosed in patients with inflammatory attacks restricted to the optic nerves and spinal cord. The chapter considers the epidemiology, pathophysiology and immunopathogenesis of NMOSD. The clinical presentation and radiographic features are reviewed and the prognosis of patients with NMOSD is considered. The mortality and morbidity of untreated NMOSD is much greater than those of MS. Treatment options are summarized and finally future prospects of research are considered.

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Detection of aquaporin-4 antibody status of Thai patients with neuromyelitis optica spectrum disorders using a recombinantEscherichia coliaquaporin-4 enzyme-linked immunosorbent assay

Clinical and Experimental Neuroimmunology ◽

10.1111/cen3.12158 ◽

2014 ◽

Vol 6 (1) ◽

pp. 57-66

Author(s):

Kulaya Kanjan ◽

Sasitorn Siritho ◽

Metha Apiwattanakul ◽

Naraporn Prayoonwiwat ◽

Panapat Uawithya

Keyword(s):

Immunosorbent Assay ◽

Neuromyelitis Optica ◽

Aquaporin 4 ◽

Enzyme Linked Immunosorbent Assay ◽

Neuromyelitis Optica Spectrum Disorders ◽

Spectrum Disorders ◽

Aquaporin 4 Antibody

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Follicular Helper CD4+T Cells in Human Neuroautoimmune Diseases and Their Animal Models

Mediators of Inflammation ◽

10.1155/2015/638968 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Xueli Fan ◽

Chenhong Lin ◽

Jinming Han ◽

Xinmei Jiang ◽

Jie Zhu ◽

...

Keyword(s):

Animal Models ◽

Neuromyelitis Optica ◽

Plasma Cells ◽

Human Peripheral Blood ◽

Lymphoid Tissues ◽

B Cell Differentiation ◽

Tfh Cells ◽

Follicular Helper ◽

Spectrum Disorders ◽

And Function

Follicular helper CD4+T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

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