Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: Roles of IL-17 and TNF-α

Gradolatto, Angéline; Nazzal, Dani; Truffault, Frédérique; Bismuth, Jacky; Fadel, Élie; Foti, Maria; Berrih‐Aknin, Sonia

doi:10.1016/j.jaut.2013.12.015

Cited by 118 publications

(113 citation statements)

References 63 publications

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“…The role of Th17 cells in the pathogenesis of autoimmune diseases and MG has been indicated in several studies [22,24,25]. Other studies have revealed that numbers of Th17 cells and associated cytokines such as IL-17 are increased in patients with MG and in animal models; this is consistent with our finding [26,27,28,29]. We also found that Th17 cell numbers were significantly decreased when compared to measurements taken 6 months after TE.…”

Section: Discussionsupporting

confidence: 92%

Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

Hosseini

Robat-Jazi

Shaygannejad

et al. 2017

Neuroimmunomodulation

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Objective: Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because most patients have thymic pathology, and thymectomy (TE) can reduce the severity of the disease. Methods: In this study, the frequency of Th17 and Tc17 cells was studied in 12 MG patients (pre-TE and 6 months post-TE) and in 12 healthy controls (HC). Results: The frequency of Tc17 cells in the pre-TE patients was significantly higher than in the HC (p < 0.05), and after TE, these cells had significantly decreased compared to before TE (p < 0.05). The frequency of Th17 cells in pre-TE patients was significantly higher than in the HC (p < 0.05), and after TE, these cells had significantly decreased compared to before TE (p < 0.05). Conclusion: Our findings indicated a possible role of Tc17 and Th17 in MG pathogenesis.

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Section: Discussionsupporting

confidence: 92%

Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

Hosseini

Robat-Jazi

Shaygannejad

et al. 2017

Neuroimmunomodulation

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“…As noted, there is evidence that AChR-associated MG is primarily mediated by Th1 T-cell responses, although there is [26,62,63]. There is additional evidence that CTLA-4 expression on T cells may be altered in MG [64].…”

Section: T-cell Signaling Pathways and Tregsmentioning

confidence: 89%

“…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%

“…There is evidence that both Th1 and Th17 T cells are involved and necessary for the AChR-specific B-cell responses in MG associated with anti-AChR antibodies [63,94]. Therefore, targeting these cells would make the most sense in this MG subset but perhaps may not be effective in MuSKpositive MG, where the role of T-cell interaction with antibody-producing B cells, and the specific subset of T cells involved, is not as well characterized.…”

Section: T Cell-b Cell Interactionsmentioning

confidence: 99%

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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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“…Consistently, it was reported that immunoregulatory defects were found in MG patients and were caused by regulatory T-cell impairment, which was supposed to be closely related with TNF-α. 26 In addition, elevated TNF-α was demonstrated to be involved in the initiation of myeloproliferative neoplasms and multiple sclerosis. 27,28 The transcriptional promoter activity of the C allele of -1031 T/C and the T allele of -857C/T in response to concanavalin A stimulation is about twofold greater than that of the dominant allele, suggesting that they might be involved in high levels of TNF-α production in immune responses to multiple stimuli.…”

Section: Discussionmentioning

confidence: 99%

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

Lei

Xie

et al. 2017

Cancer Gene Ther

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This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.

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Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: Roles of IL-17 and TNF-α

Cited by 118 publications

References 63 publications

Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

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

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

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