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This study included 51 patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) from a Japanese multicenter survey to examine clinical features and outcomes. Median onset age was 37 years and female predominance was observed. All patients developed generalized symptoms and almost all (50/51) patients had bulbar symptoms. About half of the patients met the criteria for refractory MG. The refractory group had a lower age of onset, higher severity scores, and higher maximum daily doses of oral prednisolone compared to the nonrefractory group. The outcomes for MuSK-MG patients in Japan are not favorable, indicating the need for more aggressive treatment., Competing Interests: Declaration of Competing Interest AU received honoraria from Alexion Pharmaceuticals and Argenx. SK received Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan (23FC1009) and honoraria from CSL Behring. TK reported honoraria for lectures from Argenx, Alexon Pharmaceuticals, and UCB Pharma. SS received speakers' fees from Alexion Pharmaceuticals, the Japan Blood Products Organization, Asahi Kasei Medical, and Argenx and participated in advisory board meetings of Alexion Pharmaceuticals and Argenx. MPT reported unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma, and Pfizer outside the submitted work, served as a paid Consultant for Alexion, Argenx, Sanofi, and UCB Pharma, and received an honorarium for lectures from Argenx, Alexion Pharmaceuticals, and UCB Pharma. MM received speaker honoraria from Argenx, Asahi Kasei Medical, and Alexion Pharmaceutical and participated in advisory board meetings of Alexion Pharmaceutical. YN received speaker honoraria from Argenx, Alexion Pharmaceuticals, Japan Blood Products Organization, and UCB Pharma. KU served as a paid Consultant for UCB Pharma, Janssen Pharma, Horizon Therapeutics (Viela Bio), Chugai Pharma, Hanall BioPharma, Merck, and Mitsubishi Tanabe Pharma and received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma, and the Japan Blood Products Organization. Other authors declare no financial or other conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown., Objective: To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic., Methods: We analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity., Results: In total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/- 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis., Conclusion: Iatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Antibodies against MuSK seem to be the pathogenic factor in approximately 5-8% of myasthenia gravis (MG) patients. We aim to develop an antigen-specific therapy in which only MuSK antibodies will be removed from patients' plasma using MuSK extracellular domain (MuSK-ECD) as immunoadsorbent. We showed that two different immunoadsorbents, very efficiently and selectively depleted the MuSK antibodies from all tested sera, were stable during the procedure and were reusable. Furthermore, animal experiments showed that the treatment has no toxic effects to the animals. We conclude that the MuSK-ECD-mediated immunoadsorption can be used as an efficient antigen-specific therapy for MuSK-MG., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Common marmosets, a Neotropical monkey species, are protected against clinical and neuropathological consequences of experimentally induced autoimmune encephalomyelitis (EAE) by prophylactic treatment with ch5D12, a humanized antagonist antibody against human CD40. In the current study we have tested whether ch5D12 acts therapeutically against the enlargement and inflammatory activity of existing (brain) white matter lesions using serial magnetic resonance imaging (MRI). The results show in all PBS treated monkeys (n=4) a rapid enlargement of T2 lesions together with an increment of the T2 signal intensity due to inflammatory edema. Treatment with ch5D12 delayed the enlargement of T2 lesions in 2 out of 3 tested monkeys while in 3 out of 3 monkeys the T2 signal increment of lesions was suppressed. In conjunction with previously published data on the clinical benefit of anti-CD40 treatment in the marmoset EAE model, the current findings support antibody-mediated blockade of CD40 interaction with its ligand CD154 as a potential treatment of MS.

We postulated that humoral autoimmunity can play a beneficial role in CNS demyelinating diseases such as multiple sclerosis. We previously demonstrated that monoclonal natural autoantibody SCH94.03 suppresses CNS inflammation and promotes remyelination in a virus-induced model of chronic progressive multiple sclerosis. To further investigate the relationship between natural autoimmunity and CNS demyelination, we examined the effect of SCH94.03 treatment on clinical relapses and pathological disease in SJL/J mice with established adoptive-transfer relapsing experimental autoimmune encephalomyelitis. Treatment with SCH94.03 after recovery from the initial episode of clinical disease reduced relapse rates by half, prolonged relapse onset by 6 days and reduced spinal cord demyelination and meningeal inflammation by 40%. These results are consistent with the hypothesized immunomodulatory function of natural autoantibodies, and are the first direct demonstration that natural humoral autoimmunity can be beneficial in an autoimmune T-cell-mediated CNS demyelinating disease.