Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

Chamberlain, Jayne L.; Huda, Saif; Whittam, Daniel; Matiello, Marcelo; Morgan, B. Paul; Jacob, Anu

doi:10.1007/s00415-019-09498-4

Cited by 26 publications

(29 citation statements)

References 182 publications

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“…In this analysis, eculizumab consistently reduced relapse risk in patients who were concomitantly using corticosteroids, azathioprine, or mycophenolate mofetil, as well as in those using no concomitant ISTs. Although not approved for the treatment of NMOSD, rituximab is frequently used in clinical practice (Nikoo et al, 2017), based on clinician experience and the results of mostly small, uncontrolled, or retrospective studies that suggest it to be one of the more effective agents (Bedi et al, 2011;Chamberlain et al, 2019;Cree et al, 2005;Damato et al, 2016;Jacob et al, 2008;Nikoo et al, 2017;Pellkofer et al, 2011;Poupart et al, 2020). In a recent randomized, placebo-controlled trial of 38 patients with AQP4+ NMOSD, relapse risk was reduced with rituximab versus placebo (Tahara et al, 2020).…”

Section: Encapsulated Bacterial Infections and Deathsmentioning

confidence: 99%

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Palace

Wingerchuk

Fujihara

et al. 2021

Multiple Sclerosis and Related Disorders

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Section: Encapsulated Bacterial Infections and Deathsmentioning

confidence: 99%

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Palace

Wingerchuk

Fujihara

et al. 2021

Multiple Sclerosis and Related Disorders

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“…The classic and lectin pathways are activated by known recognition molecules, such as C1q, mannose-binding lectin, and ficolins [4]. In anti-AChR antibody-positive MG, the classic pathway is primarily activated [3,[5][6][7]. Complements drive not only acute inflammatory conditions, but also several chronic disorders [8].…”

Section: Introductionmentioning

confidence: 99%

Changes in serum complements and their regulators in generalized myasthenia gravis

Ozawa

Uzawa

Yasuda

et al. 2020

Euro J of Neurology

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To investigate changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG). Methods: Forty-four patients with acetylcholine receptor antibody-positive MG, as well as 20 patients with non-inflammatory neurological disorders were enrolled. Serum complements (C3, C4 and soluble C5b-9) and complement regulators (vitronectin, clusterin and properdin) were extensively analysed by enzyme-linked immunosorbent assay and their associations with clinical profiles of MG were examined. Results: Serum C3, C4 and clusterin levels were not significantly different between patients with MG and controls. The patients with MG had higher soluble C5b-9 (P = 0.09) and vitronectin (P = 0.001) levels than the controls; moreover, vitronectin levels decreased after treatment (P = 0.09). Serum properdin (P = 0.03) levels were lower in the patients with MG than in the controls, and negatively correlated with the MG Activities of Daily Living score (rs = À0.26, P = 0.09) and with the presence of bulbar palsy (P = 0.04). Conclusion: Our results show that activation of complements and an altered complement network could contribute to the inflammatory pathogenesis of MG.

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“…As discussed above, there is compelling evidence for a central role of complement factors in NMOSD pathogenesis. Patients do not lack endogenous complement factor 1 (C1)-esterase inhibitor, but increased complement activation in acute lesions justifies its testing in NMOSD [ 184 ]. In a small study with 10 patients, the administration of a C1-esterase inhibitor, which is a nano filtered natural C1-esterase inhibitor concentrate, as add-on therapy to treatment with systemic corticosteroids was well tolerated and safe in acute NMOSD relapses.…”

Section: Current and Evolving Therapeutic Strategies In Nmosdmentioning

confidence: 99%

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

Traub¹,

Husseini

Weber

2021

Pharmaceuticals

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The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

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Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

Cited by 26 publications

References 182 publications

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Changes in serum complements and their regulators in generalized myasthenia gravis

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

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