Ofatumumab is an anti-CD20 human monoclonal antibody that is approved in several countries worldwide for the treatment of relapsing forms of multiple sclerosis (MS). Recent studies have shown promising results of ofatumumab therapy for rheumatoid arthritis (RA). We report a case with both MS and refractory RA that was successfully treated with ofatumumab.
Case Presentation
A 44-year-old woman with a history of RA since the age of 40, and prior treatment with methotrexate, prednisolone, and several disease-modifying antirheumatic drugs (DMARDs), including salazosulfapyridine, iguratimod, tacrolimus, presented with a recent onset of visual acuity loss in the left eye. Ophthalmic examination revealed a decreased central flicker frequency (CFF) and central scotoma. Brain magnetic resonance imaging (MRI) revealed periventricular multiple lesions and contrast enhancement of the left optic nerve. Cerebrospinal fluid analysis revealed mild lymphocytic pleocytosis, elevation of protein, and oligoclonal bands. Serum anti-aquaporin-4 (AQP4) antibodies, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, and other serological tests for optic neuritis were unremarkable. She was diagnosed with relapsing and remitting MS at 10 months after development of optic neuritis when she experienced a relapse, accompanied by new asymptomatic lesions detected on brain MRI. After ofatumumab administration, we discontinued all DMARDs and maintained remission over a 12-month period.
Conclusion
There is growing evidence of significant involvement of B-cells in the pathogenesis of RA and the effectiveness of B-cell depletion therapy in managing RA. Ofatumumab is an effective treatment for patients with MS and refractory RA.
{"title":"Successful treatment of multiple sclerosis with refractory rheumatoid arthritis using ofatumumab: A case report","authors":"Kenju Hara, Masaru Togashi","doi":"10.1111/cen3.12780","DOIUrl":"10.1111/cen3.12780","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ofatumumab is an anti-CD20 human monoclonal antibody that is approved in several countries worldwide for the treatment of relapsing forms of multiple sclerosis (MS). Recent studies have shown promising results of ofatumumab therapy for rheumatoid arthritis (RA). We report a case with both MS and refractory RA that was successfully treated with ofatumumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 44-year-old woman with a history of RA since the age of 40, and prior treatment with methotrexate, prednisolone, and several disease-modifying antirheumatic drugs (DMARDs), including salazosulfapyridine, iguratimod, tacrolimus, presented with a recent onset of visual acuity loss in the left eye. Ophthalmic examination revealed a decreased central flicker frequency (CFF) and central scotoma. Brain magnetic resonance imaging (MRI) revealed periventricular multiple lesions and contrast enhancement of the left optic nerve. Cerebrospinal fluid analysis revealed mild lymphocytic pleocytosis, elevation of protein, and oligoclonal bands. Serum anti-aquaporin-4 (AQP4) antibodies, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, and other serological tests for optic neuritis were unremarkable. She was diagnosed with relapsing and remitting MS at 10 months after development of optic neuritis when she experienced a relapse, accompanied by new asymptomatic lesions detected on brain MRI. After ofatumumab administration, we discontinued all DMARDs and maintained remission over a 12-month period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There is growing evidence of significant involvement of B-cells in the pathogenesis of RA and the effectiveness of B-cell depletion therapy in managing RA. Ofatumumab is an effective treatment for patients with MS and refractory RA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140452422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A thank you note to our reviewers","authors":"","doi":"10.1111/cen3.12779","DOIUrl":"https://doi.org/10.1111/cen3.12779","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The 35th annual meeting of the Japanese Society for Neuroimmunology (JSNI)","authors":"","doi":"10.1111/cen3.12778","DOIUrl":"https://doi.org/10.1111/cen3.12778","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139857978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The 35th annual meeting of the Japanese Society for Neuroimmunology (JSNI)","authors":"","doi":"10.1111/cen3.12778","DOIUrl":"10.1111/cen3.12778","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.12778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139798448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ganglionic nicotinic acetylcholine receptor (gAChR) mediates fast synaptic transmission in all peripheral autonomic ganglia (sympathetic, parasympathetic, and enteric). Over the last two decades, evidence has accumulated for a role of autoantibodies against gAChR in the development of autoimmune autonomic ganglionopathy (AAG). In this review we provide an updated overview of the field, with a highlight on the role of autoimmunity against gAChR in the pathogenesis of AAG. Clinical data as well as findings from experimental disease models are summarized in sections focusing on the presence of autoantibodies against gAChR in patients with AAG, the function of gAChR antibodies, the association of antibodies against gAChR with AAG-related phenotypes, the in vivo pathogenicity of transferred autoantibodies against gAChR in mice, and mouse models of the disease induced by immunization with the nicotinic AChR. Based on a comprehensive assessment of the currently available data, we propose a hypothetical model for the role of autoantibodies against gAChR in the pathogenesis of AAG.
{"title":"Autoantibodies against gAChR in humans and mouse models of autoimmune autonomic ganglionopathy","authors":"Shunya Nakane, Makoto Yamakawa, Yuji Nakatsuji","doi":"10.1111/cen3.12777","DOIUrl":"https://doi.org/10.1111/cen3.12777","url":null,"abstract":"<p>The ganglionic nicotinic acetylcholine receptor (gAChR) mediates fast synaptic transmission in all peripheral autonomic ganglia (sympathetic, parasympathetic, and enteric). Over the last two decades, evidence has accumulated for a role of autoantibodies against gAChR in the development of autoimmune autonomic ganglionopathy (AAG). In this review we provide an updated overview of the field, with a highlight on the role of autoimmunity against gAChR in the pathogenesis of AAG. Clinical data as well as findings from experimental disease models are summarized in sections focusing on the presence of autoantibodies against gAChR in patients with AAG, the function of gAChR antibodies, the association of antibodies against gAChR with AAG-related phenotypes, the in vivo pathogenicity of transferred autoantibodies against gAChR in mice, and mouse models of the disease induced by immunization with the nicotinic AChR. Based on a comprehensive assessment of the currently available data, we propose a hypothetical model for the role of autoantibodies against gAChR in the pathogenesis of AAG.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139719846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurologic disorders caused by autoantibodies","authors":"Yuji Nakatsuji","doi":"10.1111/cen3.12776","DOIUrl":"10.1111/cen3.12776","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139448414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD-specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.
{"title":"Myelin oligodendrocyte glycoprotein antibody-associated disorders: An overview","authors":"Tatsuro Misu, Yuki Matsumoto, Kimihiko Kaneko, Toshiyuki Takahashi, Yoshiki Takai, Hirohiko Ono, Chihiro Namatame, Shuhei Nishiyama, Juichi Fujimori, Hiroshi Kuroda, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki","doi":"10.1111/cen3.12771","DOIUrl":"10.1111/cen3.12771","url":null,"abstract":"<p>In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD-specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.12771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138959762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the John Cunningham virus. Various brain regions are affected by PML. Therefore, patients with PML show various neurological symptoms. However, tremors are rare neurological symptoms of PML.
Case Presentation
A 49-year-old man developed intermittent slow tremor in the left hand, bilateral dysesthesia and gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the right parietofrontal lobe, right thalamus, left middle cerebellar peduncle, left dentate nucleus, pons and medulla oblongata on fluid-attenuated inversion recovery images. The patient was positive for HIV antibodies. In addition, HIV-1 RNA was increased. Quantitative real-time polymerase chain reaction identified John Cunningham virus DNA in the cerebrospinal fluid; HIV-associated PML was diagnosed. Surface electromyography showed 3-Hz grouped discharges in the left flexor carpi ulnaris and extensor carpi radialis, which were consistent with Holmes tremor (HT). Although we administered antiretroviral therapy and mirtazapine, the neurological and radiological findings progressively worsened, and the patient died on day 90. Including the present case, there have been 10 reported cases of PML with HT.
Conclusions
Although tremors are rarely observed in PML, HT might be a common tremor phenotype in patients with PML. If the neurologist observes HT in patients with multiple brain lesions, PML should be considered.
{"title":"Holmes tremor in progressive multifocal leukoencephalopathy: A video case report","authors":"Takako Matsushima, Ryotaro Ikeguchi, Mutsumi Iijima, Ayato Shimomura, Shuntaro Takahashi, Kazuo Nakamichi, Yuko Shimizu, Kazuo Kitagawa","doi":"10.1111/cen3.12775","DOIUrl":"10.1111/cen3.12775","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the John Cunningham virus. Various brain regions are affected by PML. Therefore, patients with PML show various neurological symptoms. However, tremors are rare neurological symptoms of PML.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 49-year-old man developed intermittent slow tremor in the left hand, bilateral dysesthesia and gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the right parietofrontal lobe, right thalamus, left middle cerebellar peduncle, left dentate nucleus, pons and medulla oblongata on fluid-attenuated inversion recovery images. The patient was positive for HIV antibodies. In addition, HIV-1 RNA was increased. Quantitative real-time polymerase chain reaction identified John Cunningham virus DNA in the cerebrospinal fluid; HIV-associated PML was diagnosed. Surface electromyography showed 3-Hz grouped discharges in the left flexor carpi ulnaris and extensor carpi radialis, which were consistent with Holmes tremor (HT). Although we administered antiretroviral therapy and mirtazapine, the neurological and radiological findings progressively worsened, and the patient died on day 90. Including the present case, there have been 10 reported cases of PML with HT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although tremors are rarely observed in PML, HT might be a common tremor phenotype in patients with PML. If the neurologist observes HT in patients with multiple brain lesions, PML should be considered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139230789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naoki Kawaguchi, Asami Imafuku, Satoshi Fujii, Ji-Hoon Sohn
Objectives
Anti-acetylcholine receptor antibodies (AChR Ab) are one of the pathogenic autoantibodies in myasthenia gravis (MG), and they are specifically mentioned in the Japanese clinical guidelines for MG. In the serological diagnosis and measurement of autoantibodies as an adjunct marker for MG, the radioimmunoassay (RIA) method has been conventionally used as the gold standard. However, there have been several worldwide concerns regarding the use of radioisotopes. In this study, we evaluated the performance of the EUROIMMUN AChR Ab enzyme-linked immunosorbent assay (ELISA) in comparison with RIA.
Methods
ELISA reproducibility and dilution linearity were analyzed using AChR Ab-positive samples. Sera from 50 patients with suspected MG and 50 healthy donors were used to assess the correlation and qualitative agreement between the two methods.
Results
The ELISA showed good interassay precision and dilution linearity. The correlation coefficient, sensitivity, specificity and overall agreement of the ELISA in comparison with the conventional RIA amounted to 0.87, 98%, 92% and 95% (kappa = 0.895), respectively. Analysis of the discordant results suggested that the ELISA might be more capable of detecting low AChR Ab reactivity in patients with suspected MG.
Conclusions
The AchR Ab ELISA provides a reliable tool for the quantification of AchR Ab, supporting the diagnosis of MG. As a non-isotopic assay with good precision, shorter handling time and high correlation with the conventional RIA, the AChR ELISA could be a useful alternative in the laboratory routine.
{"title":"Performance evaluation of the EUROIMMUN anti-acetylcholine receptor enzyme-linked immunoassay","authors":"Naoki Kawaguchi, Asami Imafuku, Satoshi Fujii, Ji-Hoon Sohn","doi":"10.1111/cen3.12774","DOIUrl":"10.1111/cen3.12774","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Anti-acetylcholine receptor antibodies (AChR Ab) are one of the pathogenic autoantibodies in myasthenia gravis (MG), and they are specifically mentioned in the Japanese clinical guidelines for MG. In the serological diagnosis and measurement of autoantibodies as an adjunct marker for MG, the radioimmunoassay (RIA) method has been conventionally used as the gold standard. However, there have been several worldwide concerns regarding the use of radioisotopes. In this study, we evaluated the performance of the EUROIMMUN AChR Ab enzyme-linked immunosorbent assay (ELISA) in comparison with RIA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ELISA reproducibility and dilution linearity were analyzed using AChR Ab-positive samples. Sera from 50 patients with suspected MG and 50 healthy donors were used to assess the correlation and qualitative agreement between the two methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ELISA showed good interassay precision and dilution linearity. The correlation coefficient, sensitivity, specificity and overall agreement of the ELISA in comparison with the conventional RIA amounted to 0.87, 98%, 92% and 95% (kappa = 0.895), respectively. Analysis of the discordant results suggested that the ELISA might be more capable of detecting low AChR Ab reactivity in patients with suspected MG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The AchR Ab ELISA provides a reliable tool for the quantification of AchR Ab, supporting the diagnosis of MG. As a non-isotopic assay with good precision, shorter handling time and high correlation with the conventional RIA, the AChR ELISA could be a useful alternative in the laboratory routine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139257810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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