IgG regulation through FcRn blocking: A novel mechanism for the treatment of myasthenia gravis

Wolfe, Gil I.; Haard, Hans de; Ulrichts, Peter; Mozaffar, Tahseen; Pasnoor, Mamatha; Vidarsson, Gestur

doi:10.1016/j.jns.2021.118074

Cited by 36 publications

(29 citation statements)

References 84 publications

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“…It was found that the levels of IgG, IgA, IgM, complement C3, and complement C4 in peripheral blood of many patients with MGC were decreased, suggesting that immunoglobulin and complement were involved in the pathogenesis and excessive consumption. PE combined with immunoglobulin therapy can effectively enhance patients' consciousness and immune function [ 36 , 37 ]. The results of this study show that PE combined with immunoglobulin therapy can more effectively remove immunoglobulins, complements, and their immune complexes; block autoimmune response; and quickly alleviate the symptoms of MG. IgM in the PE+immunoglobulin group decreased after treatment, while that in the PE group increased after treatment.…”

Section: Discussionmentioning

confidence: 99%

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Peng

Xie

Tan

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Myasthenia gravis (MG) is an acquired autoimmune disease. The main clinical features of MG are skeletal muscle fatigue and pathological fatigue, which worsen at night or after fatigue, such as dyspnea, dysphagia, and systemic weakness. Plasma exchange (PE) is often used in patients with acute exacerbation of MG. Intravenous immunoglobulin (IVIG) is a collection of immunoglobulins from thousands of donors. IVIG can replace a variety of immunosuppressants or PE. However, the effect of PE or IVIG on patients’ consciousness, immune function, and prognosis is not clear. Objective. A prospective randomized test of the effects of PE combined with immunoglobulin on consciousness, immune function, and prognosis in patients with myasthenia gravis crisis (MGC). Methods. Sixty patients with MGC treated from February 2019 to April 2021 were enrolled in our hospital. The cases who received PE were set as the PE group, and those who received PE combined with immunoglobulin were set as the PE+immunoglobulin group. The efficacy, clinical score, state of consciousness, immune function, acetylcholine receptor antibody (AChR-Ab), lymphocyte (LYM), albumin (ALB) levels, and the incidence of adverse reactions were compared. Results. The improvement rate was 100.005% in the treatment group and 83.33% in the PE group. After treatment, the clinical score of the PE+immunoglobulin group was lower than that of the PE group, and the clinical relative score of the PE+immunoglobulin group was higher than that of the PE group ( P < 0.05 ). The number of conscious people in the PE+immunoglobulin group was more than that in the PE group ( P < 0.05 ). Immunoglobulin A, immunoglobulin M, immunoglobulin G, and immunoglobulin G in the PE+immunoglobulin group were higher than those in the PE group ( P < 0.05 ). The levels of AChR-Ab and ALB in the PE+immunoglobulin group were higher than those in the PE group, while the level of LYM in the PE+immunoglobulin group was lower than that in the PE group. The incidence of skin system, gastrointestinal system, nervous system, and systemic damage in the PE+immunoglobulin group was lower than that in the PE group ( P < 0.05 ). Conclusion. The treatment of MGC with PE combined with immunoglobulin can not only effectively enhance the consciousness and immune function of patients but also effectively promote the prognosis, and the safety of treatment can be guaranteed.

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Section: Discussionmentioning

confidence: 99%

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Peng

Xie

Tan

et al. 2022

Computational and Mathematical Methods in Medicine

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“…There was a growing number of new options for treatment of refractory MG, including neonatal Fc receptor blocking agents ( 37 ), Bortezomib [a proteasome inhibitor ( 38 )], tocilizumab [blocker of interleukin-6 ( 39 )], etc. However, few of them had been tested in trials of refractory MG. More well-designed clinical trials of these treatments on refractory MG and vigorous systemic reviews should be considered in order to establish an effective standardized treatment for patients with refractory MG.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis

Feng

Liu

et al. 2021

Front. Neurol.

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Introduction: Approximately 10–20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic review and meta-analysis to explore the optimal therapies for refractory MG.Method: Correlative studies were performed through a search in PubMed, Cochrane Library, and Embase databases. The primary outcome was defined by changes in the quantitative myasthenia gravis score (QMG). Secondary outcomes were defined by the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Myasthenia Gravis Foundation of America (MGFA) post intervention status, adverse events, and disease exacerbation after treatment.Result: A total of 16 studies were included with 403 patients with refractory MG on therapies with rituximab, eculizumab, tacrolimus, and cladribine. Therapeutic efficacy of rituximab and eculizumab was identified with an estimated reduction in QMG score (4.158 vs. 6.928) and MG-ADL (4.400 vs. 4.344), respectively. No significant changes were revealed in efficacy or exacerbation density between the two independent therapeutic cohorts. The estimated adverse event density of eculizumab was more significant than that in the rituximab group (1.195 vs. 0.134 per patient-year), while the estimated serious event density was similar.Conclusion: The efficacy and safety of rituximab and eculizumab have been approved in patients with refractory MG. Rituximab had a superior safety profile than eculizumab with a lower incidence of adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236818, identifier CRD42021236818.

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Section: Fcrn Inhibitor Treatmentsmentioning

confidence: 99%

“…Antibody-based drugs targeting the IgG binding site on FcRn are increasingly being explored to treat IgG-mediated autoimmune disorders in humans (88,89); these drugs block the interaction of FcRn with endogenous IgG. Of the FcRn inhibitors in development, some have demonstrated, in preclinical, phase 1 (Table 2), and phase 2 trials (Table 3), an effect on SA concentration as well (89). It is currently unclear whether differences in effect on SA concentration may relate to differences in FcRn inhibitor design, such as format (full-length IgG vs Fc fragment), subclass, Fc effector functions, mode of binding, affinity, pH dependency, or binding epitope.…”

Section: Fcrn Inhibitor Treatmentsmentioning

confidence: 99%

Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders

Gelinas¹,

Dreesen

Santbergen

et al. 2022

Front. Immunol.

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Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradation via a common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression.

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IgG regulation through FcRn blocking: A novel mechanism for the treatment of myasthenia gravis

Cited by 36 publications

References 84 publications

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis

Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders

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