Clinical and Experimental Neuroimmunology

Abstract The revised Japanese clinical guidelines for myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome (LEMS) were published in 2022. The notable points in these guidelines (GLs) are as follows: (i) these are the first Japanese GLs to include a description of LEMS; (ii) diagnostic criteria of MG are revised to lessen the incidence of false negative patients; (iii) MG is divided into six clinical subtypes; (iv) a high‐dose oral steroid regimen with escalation and de‐escalation schedule is not recommended by the GLs; (v) the GLs promote the early fast‐acting treatment strategy initially proposed in the previous GLs; (vi) refractory MG is defined; (vii) the use of molecular targeted drugs is included; (viii) diagnostic criteria of LEMS are proposed; and (ix) treatment algorithms for both MG and LEMS are presented. These new GLs are expected to improve the patients' quality of life and will serve to bridge the present era with the molecular targeted treatment eras.

Hiroyuki Murai

Kimiaki Utsugisawa

Masakatsu Motomura

Tomihiro Imai

Akiyuki Uzawa

Shigeaki Suzuki

The Japanese clinical guidelines 2022 for myasthenia gravis and Lambert–Eaton myasthenic syndrome

2022年日本重症肌无力和Lambert-Eaton肌无力综合征临床指南

Abstract Objectives This study aimed to validate the clinical utility of cerebrospinal fluid (CSF) CXCL10 measurements in HTLV‐1‐associated myelopathy (HAM) using a CXCL10 ELISA “Cosmic” kit, a more widely applicable method than cytometric bead array (CBA). Methods CSF CXCL10 levels were measured in 165 samples from 111 patients with HAM and 18 controls using a CXCL10 ELISA “Cosmic” kit. We assessed the following: (1) CSF CXCL10 concentrations by HAM activity level (high, moderate, and low) versus controls; (2) correlation with CBA; (3) cutoff values, sensitivity, and specificity for differentiating among HAM activity levels; (4) changes in HAM activity after steroid therapy; and (5) relationship between HAM activity and prognosis in patients undergoing steroid therapy. A correlation coefficient of ≥0.9 with CBA was the primary endpoint. Results The median CSF CXCL10 levels in the high, moderate, low, and control groups were 4016.0, 841.0, 112.8, and 102.5 pg/mL, respectively. The ELISA findings were highly correlated with the CBA findings ( r = 0.99). Cutoff values were set at 2500 pg/mL (sensitivity, 93.3%; specificity, 100%) to distinguish between high and moderate activity and 180 pg/mL (sensitivity, 81.8%; specificity, 100%) for low to moderate activity comparable to CBA. The new cutoffs enabled the detection of HAM activity changes and prediction of motor disability progression under steroid therapy. Conclusion CXCL10 ELISA “Cosmic” kit findings were strongly correlated with CBA findings, meeting the primary endpoint and demonstrating comparable sensitivity and specificity for distinguishing HAM activity. This product shows a promising ability to determine the therapeutic strategy.

Riyoko Ko

Katsunori Takahashi

Yasuo Kunitomo

Kenichiro Tanabe

Naoko Yagishita

Junji Yamauchi

Natsumi Araya

Makoto Nakashima

Erika Horibe

Takahiro Shimizu

Tomoo Sato

Yoshihisa Yamano

Performance evaluation of <scp>CXCL10 ELISA</scp> “cosmic” kit to measure <scp>CXCL10</scp> in cerebrospinal fluid of patients with <scp>HTLV</scp>‐1‐associated myelopathy

<scp>CXCL10 ELISA</scp>“宇宙”试剂盒在测量<scp>HTLV</scp>‐1相关脊髓病患者的脑脊液中<scp>CXCL10</scp>的性能评估

Abstract Background Lecanemab (Leqembi®) is an anti‐amyloid monoclonal antibody used for the treatment of Alzheimer's disease (AD). However, side effects may occur with lecanemab, including amyloid‐related imaging abnormalities (ARIA), especially in patients with apolipoprotein E ε4 ( APOE4 ) homozygous. Case Presentation A 69‐year‐old woman had a 2‐year history of worsening memory symptoms and was diagnosed with mild cognitive impairment due to AD. Because she carries two copies of the E4 allele of APOE , her doctor did not recommend lecanemab treatment. However, she strongly desired lecanemab treatment and received four infusions of lecanemab. She had no symptoms or neurological abnormalities, but a head MRI before the fifth infusion showed moderate radiographic ARIA; therefore, she was admitted and treated with steroids. One month later, a head MRI showed the ARIA had disappeared. Conclusion The indications of lecanemab treatment for patients with APOE4 homozygous must be carefully considered due to the higher risk of ARIA.

Moeko Noguchi‐Shinohara

Junji Komatsu

Kenjiro Ono

Amyloid‐related imaging abnormalities in a woman with apolipoprotein E ε4 homozygotes treated with lecanemab for <scp>Alzheimer's</scp> disease

淀粉样蛋白相关影像学异常：一名载脂蛋白E ε4纯合子接受Lecanemab治疗阿尔茨海默病患者的病例

Abstract Objective Progressive multifocal leukoencephalopathy (PML) may rarely develop in multiple sclerosis (MS) patients treated with certain disease‐modifying drugs. A female patient weighing 40 kg developed PML with 12 copies/mL of prototype JC virus (JCV) DNA in the cerebrospinal fluid after 11 y of 4 mg/kg every 6 wk with natalizumab (NTZ) and intermittent holidays of fingolimod (FTY). The aim of this study was to analyze the PML risk of this case. Methods The lymphocyte subsets of CD4 + CD62L + (central memory) and CD8 + CD62L − (effector memory) were analyzed. Additionally, the total dosage per kg for 1 y before the onset of PML and the transition of the JCV index were assessed. Results In PML‐naïve MS patients, both lymphocyte‐subset counts decreased during FTY therapy but recovered after FTY cessation. However, in this PML patient the recovery took more than 2 y. In the PML patient, the JCV index increased by 1.17 over 1 y until 10 mo before the onset of PML. Conclusions Although each factor alone is not sufficient to pose a risk in our present PML patient, the presence of multiple factors may increase the risk of PML. Administering drugs such as NTZ, which carry a PML risk, to patients with a history of FTY treatment warrants caution. Dosage and interval adjustments of NTZ should be considered. Our study suggests the possibility that FTY may increase PML risk, highlighting the importance of considering the history of immunosuppressive drug therapy when administering NTZ in MS patients.

Masami Tanaka

Kazuo Nakamichi

Keiko Tanaka

Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis treated with low‐dose natalizumab following fingolimod

多发性硬化患者从芬戈莫德转换为低剂量那他珠单抗后进行性多灶性白质脑病的风险

Abstract Background Myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs) have emerged as crucial biomarkers in idiopathic inflammatory myopathies (IIMs). Methods This review synthesizes recent research on MSAs and MAAs in various IIM subtypes. Results Specific autoantibodies correlate with distinct clinical manifestations and pathological features. For example, anti‐MDA5 antibodies are linked to rapidly progressive interstitial lung disease, while anti‐TIF1‐γ antibodies are associated with increased malignancy risk in adult dermatomyositis. Animal models have demonstrated the pathogenic potential of certain antibodies, such as anti‐TIF1‐γ, anti‐SRP, and anti‐HMGCR, in inducing experimental myositis. Conclusions Understanding the roles of MSAs and MAAs is crucial for elucidating disease mechanisms, developing targeted therapies, and improving patient outcomes. Further research is needed to fully characterize their functional implications and explore their potential as biomarkers for disease activity, prognosis, and treatment response.

Satoshi Yamashita

Myositis‐specific/associated autoantibodies as diagnostic keys and disease drivers

肌炎特异性/相关自身抗体作为诊断关键和疾病驱动因素

Abstract Objective To evaluate the responsiveness of T cells from newly diagnosed multiple sclerosis (MS) patients to CD46 co‐stimulation, a membrane co‐factor protein potentially involved in MS pathogenesis. Methods T cells from MS patients and non‐diseased symptomatic controls (SC) were activated in vitro with or without αCD46 antibody co‐stimulation. Cytokine responses were measured to assess T‐cell responsiveness. The fold difference between αCD3/CD46 and αCD3/isotype responses was calculated to determine the enhancement of CD46 activation in MS compared with SC. Additionally, the CD46 receptor phenotype, including the expression of the CD46 CYT‐1 and CYT‐2 isoforms, was analyzed. Results In the absence of αCD46 co‐stimulation, MS T cells showed weaker cytokine responses compared to SC. However, CD46 engagement neutralized this deficit, resulting in a higher fold difference in MS αCD3/CD46 responses compared to SC. MS T cells also showed a trend toward a biased CD46 receptor phenotype, with a preference for the CD46 CYT‐2 isoform. Conclusions CD46 activation enhances T‐cell responses in newly diagnosed MS patients. A bias toward the CD46 CYT‐2 isoform is observed, aligning with the previous findings that the absence of CYT‐2 downregulation in MS might contribute to a pro‐inflammatory environment.

Linda Sundvall

Litten S. Rossen

Vivien R. Schack

Bettina Bundgaard

Peter V. Rasmussen

Thor Petersen

Per Höllsberg

T cells from newly diagnosed multiple sclerosis patients have enhanced responsiveness to <scp>CD46</scp> activation

新诊断的多发性硬化症患者T细胞对<scp>CD46</scp>激活的反应性增强

ISSN	1759-1961
h-index	21

Publication Information	Publisher: John Wiley and Sons Inc，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2010，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%

Clinical and Experimental Neuroimmunology

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The Japanese clinical guidelines 2022 for myasthenia gravis and Lambert–Eaton myasthenic syndrome

Performance evaluation of CXCL10 ELISA “cosmic” kit to measure CXCL10 in cerebrospinal fluid of patients with HTLV‐1‐associated myelopathy

Amyloid‐related imaging abnormalities in a woman with apolipoprotein E ε4 homozygotes treated with lecanemab for Alzheimer's disease

Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis treated with low‐dose natalizumab following fingolimod

Myositis‐specific/associated autoantibodies as diagnostic keys and disease drivers

Amyloid‐related imaging abnormalities in a woman with apolipoprotein E ε4 homozygotes treated with lecanemab for Alzheimer's disease

Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis treated with low‐dose natalizumab following fingolimod

Performance evaluation of CXCL10 ELISA “cosmic” kit to measure CXCL10 in cerebrospinal fluid of patients with HTLV‐1‐associated myelopathy

T cells from newly diagnosed multiple sclerosis patients have enhanced responsiveness to CD46 activation

Myositis‐specific/associated autoantibodies as diagnostic keys and disease drivers