Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients

Masuda, Masayuki; Matsumoto, Masako; Tanaka, Sachiko; Nakajima, Kanako; Yamada, Naohito; Ido, Nobuhiro; Ohtsuka, Takao; Nishida, Masashi; Hirano, Toshihiko; Utsumi, Hiroya

doi:10.1016/j.jneuroim.2010.03.016

Cited by 100 publications

(92 citation statements)

References 56 publications

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“…31 Th17 cells affect the production of autoantibodies by influencing the Th1 and Th2 cytokine balance in MG patients. 32 IL-17 has been shown to synergize with BAFF to promote the survival and maturation of human B cells. 33,34 In this study, no significant difference was observed in the serum levels of IL-17A between pediatric MG patients in the pre-IST period and control subjects, which differed from that in adult MG patients.…”

Section: Discussionmentioning

confidence: 99%

An Increase in Circulating B Cell–Activating Factor in Childhood-Onset Ocular Myasthenia Gravis

Motobayashi

Inaba

Nishimura

et al. 2015

Pediatric Neurology

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Myasthenia gravis is a B cellemediated autoimmune disorder. The pathophysiology of childhoodonset ocular myasthenia gravis remains unclear. We investigated serum B celleactivating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. METHODS: Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B celleactivating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-g; tumor necrosis factor-a) as well as the percentages of peripheral blood CD4þ, CD8þ, and CD19þ cells. RESULTS: Serum B celleactivating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B celleactivating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B celleactivating factor concentrations did not correlate with the percentages of CD4þ, CD8þ, and CD19þ cells or the CD4þ/CD8þ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. CONCLUSIONS: Circulating B celleactivating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis.

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Section: Discussionmentioning

confidence: 99%

An Increase in Circulating B Cell–Activating Factor in Childhood-Onset Ocular Myasthenia Gravis

Motobayashi

Inaba

Nishimura

et al. 2015

Pediatric Neurology

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“…An extension of these observations is that defects in Treg number or function may underlie the development of human autoimmune disorders. Importantly, Tregs have been implicated in preventing autoantibody production by self-reactive B cells [75][76][77], and dysfunction or deficiencies of Tregs have been demonstrated in MG [63,[78][79][80][81].…”

Section: T-cell Signaling Pathways and Tregsmentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

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“…One study used a more precise method for detection, including the detection of cells with FOXP3 surface protein and CD25+ (high), and it also showed a reduction in the frequency of T-regs in MG patients compared to healthy controls (28). Moreover, Masuda et al found that FOXP3 expression and T-regs number were lower in MG patients than in healthy controls (29). Other studies have shown only dysfunction in Tregs activity.…”

Section: Discussionmentioning

confidence: 99%

“…There are many reports that showed decreased number or activity of T-regs in animal models of MG (23)(24)(25)(26), however limited number of reports studied the T-regs in human patients with MG with conflicting results. Some studies showed reductions in T-regs numbers (27)(28)(29), impairment of its regulatory function (30,31), or no defect (32,33). One more mechanism of defense against immune attacks of self-antigens is the complement regulatory proteins.…”

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confidence: 99%

The potential role of cell surface complement regulators and circulating cd4+ cd25+ t-cells in the development of autoimmune myasthenia gravis

Thabit

Fattouh

Nasreldin

2015

Journal of the Neurological Sciences

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Introduction: CD4+CD25+ regulatory T-lymphocytes (T-regs) and regulators of complement activity (RCA) involving CD55 and CD59 play an important role in the prevention of autoimmune diseases. However, their role in the pathogenesis of human autoimmune myasthenia gravis (MG) remains unclear. This study aimed to determine the frequency of peripheral blood T-regs and CD4+ T-helper (T-helper) cells and the red blood cells (RBCs) level of expression of CD55 and CD59 in MG patients. Methods: Fourteen patients with MG in neurology outpatient clinics of Sohag University Hospital and Sohag General Hospital from March 2014 to December 2014, and 10 age-matched healthy controls participated in this case-control study. We did flowcytometric assessments of the percentage of peripheral T-regs and T-helper cells and the level of expression of CD55 and CD59 on RBCs in the peripheral blood of patients and controls. Results: There was a statistically significant decrease in the percentage of peripheral blood T-regs and T-regs/Thelper cell ratio in the MG patients group. Moreover, the level of expression of CD55, CD59, and dual expression of CD55/CD59 on RBCs were statistically significantly lower in MG patients than those of healthy controls. However, regression analysis indicated that there was no significant correlation between all the measured parameters and disease duration or staging. Conclusion: Functional defects in the T-regs and RCA may play a role in the pathogenesis of autoimmune MG and their functional modulation may represent an alternative therapeutic strategy for MG treatment.

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Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients

Cited by 100 publications

References 56 publications

An Increase in Circulating B Cell–Activating Factor in Childhood-Onset Ocular Myasthenia Gravis

An Increase in Circulating B Cell–Activating Factor in Childhood-Onset Ocular Myasthenia Gravis

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

The potential role of cell surface complement regulators and circulating cd4+ cd25+ t-cells in the development of autoimmune myasthenia gravis

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