B cell targeted therapies in inflammatory autoimmune disease of the central nervous system

Furman, Moritz J.; Meuth, Sven G.; Albrecht, Philipp; Dietrich, Michael; Blum, Heike; Mareś, Jan; Milo, Ron; Hartung, Hans‐Peter

doi:10.3389/fimmu.2023.1129906

Cited by 11 publications

(6 citation statements)

References 135 publications

(235 reference statements)

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“…Anti‐CD20 therapy (rituximab, ocrelizumab, and ofatumumab) was linked with higher COVID‐19 experience and severity 25,26 . Anti‐CD19 antibody monotherapy (Inebilizumab) also produced similar outcomes to COVID‐19, since antibody generation and responses to COVID‐19 vaccinations were hampered when treated with B‐cell‐depleting therapies 27 . Anti‐CD20 and anti‐CD19 therapy may increase the incidence of COVID‐19 in NMOSD patients, but this is questionable and requires further research.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Choi,

Ai,

et al. 2024

Immunity Inflam & Disease

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IntroductionTo evaluate whether treated with immunosuppressants in neuromyelitis optica spectrum disorder (NMOSD) shows an effect on the severity and outcomes of COVID‐19 Omicron variant.MethodsThis is a substudy of a single‐center clinical trial involving human umbilical cord mesenchymal stem cells (hUC‐MSCs) in NMOSD patients. NMOSD patients with hUC‐MSCs treatment, NMOSD patients without hUC‐MSCs treatment, and matched healthy controls (HC) were included. Demographic information, NMOSD‐related clinical features, comorbidities, use of disease‐modifying therapy, COVID‐19 vaccination status, COVID‐19 clinical features, COVID‐19 clinical outcomes, and NMOSD‐related disease activity were obtained through online questionnaires or phone calls.ResultsThe majority of NMOSD patients received long‐term treatment with mycophenolate mofetil (68.8%) or azathioprine (22.9%), and 50% received oral glucocorticoid. During the epidemic, 97.4% of NMOSD patients infected with COVID‐19 had asymptomatic or mild forms, with only two patients (2.6%) requiring hospitalization. None of these patients required tracheal intubation or admission to the intensive care unit. Clinical symptoms were found to be more prevalent in HC groups. Additionally, the HC groups had higher fever‐recorded temperatures. NMOSD patients who received hUC‐MSCs treatment had shorter disease duration than patients who did not receive hUC‐MSCs treatment.DiscussionImmunosuppressant‐treated patients with NMOSD have a similar risk of COVID‐19 infection as the general population, but the disease duration is shorter and the clinical symptoms are less severe. Among our NMOSD patients who received hUC‐MSCs treatment, COVID‐19 outcomes were favorable, with no increased risk of severe COVID‐19. Prospective studies on immunotherapies are needed to help determine best treatment practices.

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Choi,

Ai,

et al. 2024

Immunity Inflam & Disease

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“…Unlike NMOSD and MOGAD, which exhibit clear antibody associations, MS has traditionally been seen as a T-cell-driven disease. Nevertheless, recent developments in B-cell-targeted therapies have stimulated interest in exploring the regulatory and antigen-presenting roles of B cells [32]. This emphasizes the dysregulation of both cell-mediated and humoral components of the adaptive immune system in these disorders.…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders

Cossu,

Tomizawa,

Sechi

et al. 2023

IJMS

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Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocytes glycoprotein-antibody disease (MOGAD) are distinct autoimmune demyelinating disorders characterized by varying clinical and pathological characteristics. While the precise origins of these diseases remain elusive, a combination of genetic and environmental factors, including viral elements, have been suggested as potential contributors to their development. Our goal was to assess the occurrence of antibodies against pathogenic peptides associated with Epstein–Barr virus (EBV) and the human endogenous retrovirus-W (HERV-W) in serum samples obtained from Japanese individuals diagnosed with MS, NMOSD, and MOGAD and to make comparisons with a group of healthy controls (HCs). We conducted a retrospective analysis involving 114 Japanese participants, comprising individuals with MS (34), NMOSD (20), MOGAD (20), and HCs (40). These individuals were tested using a peptide-based enzyme-linked immunosorbent assay. A marked increase in antibody response against EBV nuclear antigen 1 (EBNA1)386–405 was observed in the serum of MS and MOGAD patients, as compared to HCs. Notably, we observed a correlation between antibodies against EBNA1386–405 and HERV-W486–504 peptides in a subset of the antibody-positive MS patients. These findings emphasize the involvement of EBV in the pathogenesis of MS and potentially MOGAD, suggesting its role in the reactivation of HERV-W.

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“…Other BTK inhibitors are being studied in multiple sclerosis 88,89 and NMO (neuromyelitis optica)-spectrum disorders. 90 There are no current trials in CIDP, although this is a potentially important drug class for future consideration and availability of long-term data on haematological disorders may facilitate their application in the field of inflammatory neuropathy. 91,92…”

Section: Bruton Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks

Rajabally

2024

ITT

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current first-line evidence-based therapies for CIDP include intravenous and subcutaneous immunoglobulins, corticosteroids and plasma exchanges. Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies. Rituximab is currently the object of a randomized controlled trial for CIDP. Based on case series, and although rarely considered, haematopoietic autologous stem cell transplants may be effective in refractory disease, with low mortality and high remission rates. A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP.

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B cell targeted therapies in inflammatory autoimmune disease of the central nervous system

Cited by 11 publications

References 135 publications

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Epstein–Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks

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