A Potential Role for B-Cell Activating Factor in the Pathogenesis of Autoimmune Myasthenia Gravis

Ragheb, Samia; Lisak, Robert P.; Lewis, Richard A.; Stavern, Gregory Van; Gonzales, Felicitas; Simon, Kirk

doi:10.1001/archneur.65.10.1358

Cited by 60 publications

(55 citation statements)

References 31 publications

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“…3,4 Additionally, increased levels of serum BAFF have been detected in patients with autoimmune disorders including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, Wegener granulomatosis, and adult MG. 4,8,[20][21][22] Thus, BAFF appears to protect autoreactive B cells from apoptosis and contribute to the development of autoimmune diseases. 9,23,24 On the other hand, circulating BAFF kinetics have not been reported in childhood-onset MG. In the present study, serum BAFF levels were significantly higher before IST in children with ocular MG than in controls; these decreased after IST.…”

Section: Discussionmentioning

confidence: 99%

“…These results are consistent with previous findings obtained from adult MG patients. [8][9][10] Thus, BAFF may play a key role in the pathogenesis of pediatric MG as well as adult MG. In addition, BAFF could be surrogate marker for therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrated that serum BAFF levels were significantly higher in adult patients with MG than in controls. [8][9][10] Childhood-onset MG is a relatively uncommon disease, with an estimated incidence of 3-9.1 per million per year, 11 and the relationship between BAFF and childhoodonset MG remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

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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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“…Studies have shown that serum levels of BAFF are elevated in patients with AChR and MuSK MG, and that these levels may be particularly elevated in patients with active anti-AChRpositive disease [106,107]. A human monoclonal antibody targeting BAFF, belimumab, has been approved for the treatment of lupus erythematosus [108].…”

Section: B Cells B-cell Trophic Factors and Plasma Cellsmentioning

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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“…Depleting or suppressing B-cell function may therefore restore immune balance. BAFF levels are also relevant, as they have been found to be increased in active disease [86].…”

Section: Mgmentioning

confidence: 99%

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

2016

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B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or Bcell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.

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A Potential Role for B-Cell Activating Factor in the Pathogenesis of Autoimmune Myasthenia Gravis

Cited by 60 publications

References 31 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

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

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