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Article ; Online: Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts.

Ma, Xue / Bu, Bi-Tao

2022 Volume 13, Page(s) 1019972

Abstract: Purpose of review: This review aims to describe clinical and histological features, treatment, and prognosis in patients with anti-signal recognition particle (SRP) autoantibodies positive immune-mediated necrotizing myopathy (SRP-IMNM) based on ... ...

Abstract	Purpose of review: This review aims to describe clinical and histological features, treatment, and prognosis in patients with anti-signal recognition particle (SRP) autoantibodies positive immune-mediated necrotizing myopathy (SRP-IMNM) based on previous findings. Previous findings: Anti-SRP autoantibodies are specific in IMNM. Humoral autoimmune and inflammatory responses are the main autoimmune characteristics of SRP-IMNM. SRP-IMNM is clinically characterized by acute or subacute, moderately severe, symmetrical proximal weakness. Younger patients with SRP-IMNM tend to have more severe clinical symptoms. Patients with SRP-IMNM may be vulnerable to cardiac involvement, which ought to be regularly monitored and cardiac magnetic resonance imaging is the recommended detection method. The pathological features of SRP-IMNM are patchy or diffuse myonecrosis and myoregeneration accompanied by a paucity of inflammatory infiltrates. Endoplasmic reticulum stress-induced autophagy pathway and necroptosis are activated in skeletal muscle of SRP-IMNM. Treatment of refractory SRP-IMNM encounters resistance and warrants further investigation. Summary: Anti-SRP autoantibodies define a unique population of IMNM patients. The immune and non-immune pathophysiological mechanisms are involved in SRP-IMNM.
MeSH term(s)	Humans ; Signal Recognition Particle ; Necrosis ; Myositis ; Autoimmune Diseases ; Autoantibodies ; Muscular Diseases/therapy
Chemical Substances	Signal Recognition Particle ; Autoantibodies
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1019972
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Article ; Online: Interleukin-6 trans-signaling regulates monocyte chemoattractant protein-1 production in immune-mediated necrotizing myopathy.

Ma, Xue / Gao, Hua-Jie / Ge, Hui-Zhen / Zhang, Qing / Bu, Bi-Tao

Rheumatology (Oxford, England)

2024

Abstract: Objective: Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofiber necrosis and regeneration, myophagocytosis, and a sparse inflammatory infiltrate. The monocyte chemoattractant protein-1 (MCP-1) is a key ... ...

Abstract	Objective: Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofiber necrosis and regeneration, myophagocytosis, and a sparse inflammatory infiltrate. The monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that regulates monocyte/macrophage infiltration into injured tissues. The interleukin-6 (IL-6) signalling in the induction of MCP-1 expression has not been investigated in IMNM. Methods: MCP-1 expression in muscle specimens was assessed using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated using the Meso Scale Discovery electrochemiluminescence system. Flow cytometry, RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase reporter assays, and chromatin immunoprecipitation-qPCR were performed to explore the effects of IL-6 signalling on MCP-1 production in human myoblasts. Results: MCP-1 was scattered and was positively expressed within myofibers and a few inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 expression significantly correlated with myonecrosis, myoregeneration, and inflammatory infiltration. Serum MCP-1, IL-6, and the soluble form of the IL-6 receptor (sIL-6R) were elevated in patients with IMNM compared with controls. Serological MCP-1 levels were significantly associated with serum IL-6 expression and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced MCP-1 expression via the signal transducer and activator of transcription 3 (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched in the MCP-1 promoter region and promoted the transcription. Conclusion: IL-6 trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting inflammation through regulation of MCP-1 expression in IMNM.
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae118
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: The diagnostic value of serum YKL-40 for myocardial involvement in immune-mediated necrotising myopathy.

Xu, Li / Yang, Meng-Ge / Hu, Shejing / Li, Yue / Bu, Bi-Tao / Ji, Suqiong

Clinical and experimental rheumatology

2023 Volume 42, Issue 2, Page(s) 329–336

Abstract: Objectives: This study aimed to determine the diagnostic value of YKL-40 for myocardial involvement in immune-mediated necrotising myopathy (IMNM).: Methods: We retrospectively analysed the data of patients with IMNM admitted to the Neurology ... ...

Abstract	Objectives: This study aimed to determine the diagnostic value of YKL-40 for myocardial involvement in immune-mediated necrotising myopathy (IMNM). Methods: We retrospectively analysed the data of patients with IMNM admitted to the Neurology Department at Tongji Hospital between April 2013 and August 2022. Clinical data including patients' demographics, clinical characteristics (disease duration, muscle strength, atrophy, rash, dysphagia, dyspnoea, and myalgia) and laboratory test results were collected from the electronic medical record system. Serum YKL-40 levels were measured using an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve was drawn, and the area under the ROC curve was calculated to evaluate the diagnostic value of YKL-40 for cardiac involvement in IMNM. Results: 29 patients with IMNM and15 sex and age-matched volunteers without history of heart diseases were recruited for the study. Compared with the healthy controls, serum YKL-40 levels were notably up-regulated [96.3 (55.5 120.6) pg/ml versus 19.6 (13.8 20.9) pg/ml; p=0.000] in patients with IMNM. We compared 14 patients with IMNM with cardiac abnormalities and 15 patients with IMNM without cardiac abnormalities. The most important finding was that serum YKL-40 levels were higher in the patients with IMNM with cardiac involvement based on cardiac magnetic resonance (CMR) examination [119.2 (88.4 185.69) pm/ml versus 72.5 (35.7 98) pm/ml; p=0.002]. YKL-40 had a specificity and sensitivity of 86.7% and 71.4% respectively, at a cut-off value of 105.46 pg/ml for predicting myocardial injury in patients with IMNM. Conclusions: YKL-40 could be a promising non-invasive biomarker for diagnosing myocardial involvement in IMNM. However, larger prospective study is warranted.
MeSH term(s)	Humans ; Chitinase-3-Like Protein 1 ; Retrospective Studies ; Prospective Studies ; Myositis/diagnosis ; Autoimmune Diseases
Chemical Substances	Chitinase-3-Like Protein 1
Language	English
Publishing date	2023-06-06
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/itrujk
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Article: A Comparison of IgG Index and Oligoclonal Band in the Cerebrospinal Fluid for Differentiating between RRMS and NMOSD.

Chen, Bo / Tian, Dai-Shi / Bu, Bi-Tao

Brain sciences

2021 Volume 12, Issue 1

Abstract: As the oligoclonal band in the cerebrospinal fluid (CSF-OCB) in predicting relapsing-remitting multiple sclerosis (RRMS) is less sensitive in Asian populations than that in westerners, it remains elusive whether the IgG index could serve as an ... ...

Abstract	As the oligoclonal band in the cerebrospinal fluid (CSF-OCB) in predicting relapsing-remitting multiple sclerosis (RRMS) is less sensitive in Asian populations than that in westerners, it remains elusive whether the IgG index could serve as an alternative. The purpose of this study was to compare these two methods of differentiating between RRMS and neuromyelitis optica spectrum disorder (NMOSD) in Chinese patients. A total of 171 patients (81 RRMS and 90 NMOSD) were retrospectively recruited, of whom 82 (56 RRMS and 26 NMOSD) received the CSF-OCB testing additionally. When the onset age was ≤38.5 years, IgG index with the threshold of 0.67 had a significant agreement (k = 0.4,
Language	English
Publishing date	2021-12-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12010069
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Article ; Online: Immunological predictors for the outcome in patients with antibody-mediated autoimmune encephalitis.

Chen, Bo / Tian, Dai-Shi / Bu, Bi-Tao

Journal of neuroimmunology

2021 Volume 362, Page(s) 577779

Abstract: We investigated the immunological outcome predictors in patients with antibody-mediated autoimmune encephalitis. A severe disability on admission, a low lymphocyte count, including T, B, and T + B + NK (TBNK) cells, an elevated neutrophil (%) and ... ...

Abstract	We investigated the immunological outcome predictors in patients with antibody-mediated autoimmune encephalitis. A severe disability on admission, a low lymphocyte count, including T, B, and T + B + NK (TBNK) cells, an elevated neutrophil (%) and neutrophil to lymphocyte ratio (NLR) could predict poor prognoses. The increased neutrophils (%) and NLR with the decreased eosinophil percent and count were sensitive (>0.8) in predicting severe disabilities, while the declined total T cell count, lymphocyte percent and count were specific (>0.9). TBNK cell count had a balanced sensitivity and specificity (both>0.8). Patients with autoimmune encephalitis with poor outcomes are immunologically distinct from those with good recoveries.
MeSH term(s)	Adult ; Autoimmune Diseases of the Nervous System/immunology ; Encephalitis/immunology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Recovery of Function/immunology ; Retrospective Studies
Language	English
Publishing date	2021-11-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2021.577779
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Article ; Online: Contribution of relapse-associated worsening to overall disability accrual in patients with relapsing-onset multiple sclerosis: A mediation analysis.

Chen, Bo / Ji, Su-Qiong / Shen, Fan / Tian, Dai-Shi / Bu, Bi-Tao

Multiple sclerosis and related disorders

2022 Volume 59, Page(s) 103555

Abstract: Objective: The neurological disability accumulation in patients with relapsing-onset multiple sclerosis (MS) is commonly attributed to relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Using a mediation model, ... ...

Abstract	Objective: The neurological disability accumulation in patients with relapsing-onset multiple sclerosis (MS) is commonly attributed to relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Using a mediation model, this research aimed to investigate and quantify the contributions of RAW and PIRA to the overall disability accrual. Methods: Clinical data, containing Expanded Disability Status Scale (EDSS) scores, duration, attack number, and demographics, were collected from 121 patients with relapsing-onset MS in China and included in the mediation model. Two phases were defined: an early phase, from the clinical onset to EDSS 3, and a later phase, greater than EDSS 3. Results: Clinical attack number partly mediated the relationship between duration and neurological disability (Duration → Attack → EDSS score) only in the early phase, with the ratio of indirect (RAW) to total effect of 0.414; while this mediator effect became negligible (<10%) in the later phase, with a predominating direct effect (PIRA). Onset age positively correlated with EDSS scores during the early stage, independent of the clinical attack number (the direct effect was significant, but the indirect effect was not), while this association was insignificant later. Besides, compared to females, male patients appeared to relapse less frequently before reaching EDSS 3 but were vulnerable to an accelerated progression after that. Conclusions: In relapsing-onset MS, PIRA is the major contributor to the irreversible disability accrual throughout the whole disease course, albeit RAW is also partly involved during the early stage. The correlations between the disabled outcome and the onset age or sex vary in different phases.
MeSH term(s)	Disability Evaluation ; Disabled Persons ; Disease Progression ; Female ; Humans ; Male ; Mediation Analysis ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting ; Recurrence
Language	English
Publishing date	2022-01-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.103555
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Article ; Online: Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy.

Qin, Chuan / Dong, Ming-Hao / Zhou, Luo-Qi / Wang, Wen / Cai, Song-Bai / You, Yun-Fan / Shang, Ke / Xiao, Jun / Wang, Di / Li, Chun-Rui / Zhang, Min / Bu, Bi-Tao / Tian, Dai-Shi / Wang, Wei

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 6, Page(s) e2315990121

Abstract: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation with rapidly progressive muscular weakness and elevated levels of creatine kinase, while ... ...

Abstract	Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation with rapidly progressive muscular weakness and elevated levels of creatine kinase, while traditional pharmacological approaches possess varying and often limited effects. Considering the pathogenic role of autoantibodies, chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA) have emerged as a promising therapeutic strategy. We reported here a patient with anti-signal recognition particle IMNM refractory to multiple available therapies, who was treated with BCMA-targeting CAR-T cells, exhibited favorable safety profiles, sustained reduction in pathogenic autoantibodies, and persistent clinical improvements over 18 mo. Longitudinal single-cell RNA, B cell receptor, T cell receptor sequencing analysis presented the normalization of immune microenvironment after CAR-T cell infusion, including reconstitution of B cell lineages, replacement of T cell subclusters, and suppression of overactivated immune cells. Analysis on characteristics of CAR-T cells in IMNM demonstrated a more active expansion of CD8
MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Multiple Myeloma/drug therapy ; B-Cell Maturation Antigen ; Neuroinflammatory Diseases ; Immunotherapy, Adoptive ; Autoimmune Diseases/therapy ; Autoantibodies ; Muscular Diseases/therapy ; Single-Cell Analysis ; Cell- and Tissue-Based Therapy ; Tumor Microenvironment
Chemical Substances	Receptors, Chimeric Antigen ; B-Cell Maturation Antigen ; Autoantibodies
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2315990121
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Article ; Online: Distinct Immunological Features of Inflammatory Demyelinating Diseases of the Central Nervous System.

Chen, Bo / Gui, Meng-Cui / Ji, Su-Qiong / Xie, Yi / Tian, Dai-Shi / Bu, Bi-Tao

Neuroimmunomodulation

2021 Volume 29, Issue 3, Page(s) 220–230

Abstract: Objective: The immunological features between neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lacked systemic comparisons. Accordingly, we aimed to ... ...

Abstract	Objective: The immunological features between neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lacked systemic comparisons. Accordingly, we aimed to investigate immunological differences between NMOSD, MS, and MOGAD. Methods: Patients with MOGAD, MS, and NMOSD who received immunological tests including cytokine profiles and cytometry analysis of the lymphocyte subgroups were retrospectively reviewed and divided into training and validation sets. Discriminatory models based on immunological data were established to identify optimal classifiers using orthogonal partial least square discriminant analysis (OPLS-DA). Constructed models were tested in another independent cohort. Results: OPLS-DA of the immunological data from 50 patients (26 NMOSD, 14 MS, and 10 MOGAD) demonstrated the discriminatory values of a relatively low level of T-lymphocyte subsets, especially the CD4+ T cells, in MOGAD; a decreased NK cell, eosinophil, and lymphocyte level; an elevated neutrophil-to-lymphocyte ratio in NMOSD; and a declined IFN-γ-producing CD4+ T cells/Th with an increased IL-8 concentration in MS. All the models (NMOSD vs. MS, NMOSD vs. MOGAD, and MS vs. MOGAD) exhibited a significant predictive value and accuracy (>85%). Conclusions: NMOSD, MS, and MOGAD may be different in pathogenesis, and several immunological biomarkers can serve as potential classifiers clinically.
MeSH term(s)	Aquaporin 4 ; Autoantibodies ; Central Nervous System/pathology ; Humans ; Multiple Sclerosis/diagnosis ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Retrospective Studies
Chemical Substances	Aquaporin 4 ; Autoantibodies ; Myelin-Oligodendrocyte Glycoprotein
Language	English
Publishing date	2021-11-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1184368-8
ISSN	1423-0216 ; 1021-7401
ISSN (online)	1423-0216
ISSN	1021-7401
DOI	10.1159/000519835
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Article ; Online: B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

Tian, Dai-Shi / Qin, Chuan / Dong, Ming-Hao / Heming, Michael / Zhou, Luo-Qi / Wang, Wen / Cai, Song-Bai / You, Yun-Fan / Shang, Ke / Xiao, Jun / Wang, Di / Li, Chun-Rui / Zhang, Min / Bu, Bi-Tao / Meyer Zu Hörste, Gerd / Wang, Wei

EMBO molecular medicine

2024 Volume 16, Issue 4, Page(s) 966–987

Abstract: B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly ... ...

Abstract	B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms underlying the therapeutic efficacy of CAR-T cells in these patients, longitudinal single-cell RNA and TCR sequencing was conducted on serial blood samples post infusion as well as their matching infusion products. By tracking the temporal evolution of CAR-T phenotypes, we demonstrated that proliferating cytotoxic-like CD8 clones were the main effectors in autoimmunity, whereas compromised cytotoxic and proliferation signature and profound mitochondrial dysfunction in CD8
MeSH term(s)	Humans ; Immunotherapy, Adoptive ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Multiple Myeloma/therapy ; B-Cell Maturation Antigen/genetics ; Cell Lineage ; Myasthenia Gravis/therapy ; T-Lymphocytes ; Immunoglobulin G
Chemical Substances	B-Cell Maturation Antigen ; Immunoglobulin G
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.1038/s44321-024-00043-z
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Article ; Online: Aquaporin-4 antibody positive neuromyelitis optica spectrum disorder subsequent to rhabdomyolysis: a case report and literature review.

Shang, Ke / Qin, Chuan / Bu, Bi-Tao / Tian, Dai-Shi

The International journal of neuroscience

2019 Volume 129, Issue 9, Page(s) 930–932

Abstract: Rhabdomyolysis could be caused by various mechanisms including autoimmune reaction. Here, we reported a case of 76-year-old-woman diagnosed with aquaporin-4 (AQP4) IgG positive neuromyelitis optica spectrum disorder (NMOSD) following rhabdomyolysis. ... ...

Abstract	Rhabdomyolysis could be caused by various mechanisms including autoimmune reaction. Here, we reported a case of 76-year-old-woman diagnosed with aquaporin-4 (AQP4) IgG positive neuromyelitis optica spectrum disorder (NMOSD) following rhabdomyolysis. After a review of literature, we propose that physical injury of skeletal muscle cells may lead to the production of AQP4 IgG and this AQP4 IgG might further decrease in the stability of skeletal muscle cells creating a positive feedback loop. HyperCKemia might be an inducement of NMOSD.
MeSH term(s)	Aged ; Aquaporin 4/blood ; Autoantibodies/blood ; Female ; Humans ; Neuromyelitis Optica/blood ; Neuromyelitis Optica/diagnostic imaging ; Neuromyelitis Optica/etiology ; Rhabdomyolysis/blood ; Rhabdomyolysis/complications ; Rhabdomyolysis/diagnostic imaging
Chemical Substances	AQP4 protein, human ; Aquaporin 4 ; Autoantibodies
Language	English
Publishing date	2019-03-01
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	3061-2
ISSN	1563-5279 ; 1543-5245 ; 0020-7454
ISSN (online)	1563-5279 ; 1543-5245
ISSN	0020-7454
DOI	10.1080/00207454.2019.1579718
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