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Traditional pediatric massage exerted an antidepressant effect and activated IGF-1/Nrf2 pathway in CUMS-exposed adolescent rats
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.jneuroim.2025.578554
Xingxing Zhang , Que Liu , Siyuan Li , Rong Wu , Ying Xiong , Yuhang Wang , Yun Gu , Zhixiu Song , Jiaxuan Gong , Shaoyun Zhao
The activation of insulin-like growth factor-1 (IGF-1)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway contributes to enhance anti-inflammatory M2 microglia polarization and inhibit proinflammatory M1 microglia polarization, which is essential to resist neuroinflammation and thus resist depression. The prevalence of depression is high in adolescents, who are hypersensitive to chronic stress. Traditional pediatric massage (TPM) can effectively relieve depression. In this study, we investigated the action mechanism of TPM on preventing depression-like behaviors in adolescent rats exposed to chronic unpredictable mild stress (CUMS). In this investigation, we employed several behavioral tests and detections, including western blotting, immunofluorescence staining and RT-qPCR. The findings of this study demonstrated that TPM had an effectively antidepressant effect, maintained microglia polarization homeostasis and resisted neuroinflammation in the hippocampus in CUMS-exposed adolescent rats. With the treatment of picropodophyllin, the inhibitor of IGF-1 receptor, the antidepressant effect of TPM was blocked, along with inhibited IGF-1/Nrf2 pathway which were closely related with anti-inflammatory and anti-ferroptosis actions. The results suggest that TPM enhanced the resilience of adolescent rats to CUMS and exerted an antidepressant effect partially via activating IGF-1/Nrf2 pathway.
胰岛素样生长因子-1(IGF-1)/核因子-红细胞 2 相关因子 2(Nrf2)通路的激活有助于增强抗炎性 M2 小胶质细胞的极化,抑制促炎性 M1 小胶质细胞的极化,这对于抵御神经炎症进而抵御抑郁症至关重要。青少年是抑郁症的高发人群,他们对慢性压力非常敏感。传统小儿推拿(TPM)能有效缓解抑郁。在本研究中,我们探讨了传统小儿推拿对暴露于慢性不可预测轻度应激(CUMS)的青少年大鼠预防抑郁样行为的作用机制。在这项研究中,我们采用了多种行为测试和检测方法,包括西方印迹、免疫荧光染色和 RT-qPCR。研究结果表明,TPM具有有效的抗抑郁作用,能维持小胶质细胞极化平衡,并能抵抗CUMS暴露的青少年大鼠海马中的神经炎症。在IGF-1受体抑制剂吡咯茶碱的作用下,TPM的抗抑郁作用被阻断,同时IGF-1/Nrf2通路也被抑制,而IGF-1/Nrf2通路与抗炎和抗铁锈色素沉着作用密切相关。结果表明,TPM能增强青春期大鼠对CUMS的恢复能力,并部分通过激活IGF-1/Nrf2途径发挥抗抑郁作用。
{"title":"Traditional pediatric massage exerted an antidepressant effect and activated IGF-1/Nrf2 pathway in CUMS-exposed adolescent rats","authors":"Xingxing Zhang ,&nbsp;Que Liu ,&nbsp;Siyuan Li ,&nbsp;Rong Wu ,&nbsp;Ying Xiong ,&nbsp;Yuhang Wang ,&nbsp;Yun Gu ,&nbsp;Zhixiu Song ,&nbsp;Jiaxuan Gong ,&nbsp;Shaoyun Zhao","doi":"10.1016/j.jneuroim.2025.578554","DOIUrl":"10.1016/j.jneuroim.2025.578554","url":null,"abstract":"<div><div>The activation of insulin-like growth factor-1 (IGF-1)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway contributes to enhance anti-inflammatory M2 microglia polarization and inhibit proinflammatory M1 microglia polarization, which is essential to resist neuroinflammation and thus resist depression. The prevalence of depression is high in adolescents, who are hypersensitive to chronic stress. Traditional pediatric massage (TPM) can effectively relieve depression. In this study, we investigated the action mechanism of TPM on preventing depression-like behaviors in adolescent rats exposed to chronic unpredictable mild stress (CUMS). In this investigation, we employed several behavioral tests and detections, including western blotting, immunofluorescence staining and RT-qPCR. The findings of this study demonstrated that TPM had an effectively antidepressant effect, maintained microglia polarization homeostasis and resisted neuroinflammation in the hippocampus in CUMS-exposed adolescent rats. With the treatment of picropodophyllin, the inhibitor of IGF-1 receptor, the antidepressant effect of TPM was blocked, along with inhibited IGF-1/Nrf2 pathway which were closely related with anti-inflammatory and anti-ferroptosis actions. The results suggest that TPM enhanced the resilience of adolescent rats to CUMS and exerted an antidepressant effect partially via activating IGF-1/Nrf2 pathway.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578554"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rheumatoid meningitis in the absence of active synovitis: A potential association of semaphorin 4A
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-09 DOI: 10.1016/j.jneuroim.2025.578548
Keishu Murakami , Yoshiaki Nakayama , Shigeru Iwata , Seiji Emori , Shoko Yorozu , Takao Fujii , Katsuichi Miyamoto
Rheumatoid meningitis (RM) is a rare complication that can develop even in patients with inactive rheumatoid arthritis (RA). Currently, there are no reliable indicators that reflect the disease activity of RM, and its pathogenesis remains poorly understood. Herein, we presented three cases of RM without active synovitis and investigated the possible association between RM and semaphorin 4A (Sema4A). Two of the three patients with RM developed sudden onset of seizures, while one patient exhibited a slowly progressive gait disturbance and cognitive impairment. All the patients had inactive synovitis, positive anti-cyclic citrullinated peptide antibodies in the serum, high-intensity lesions on the cerebral surface on head magnetic resonance imaging, or a favorable response to glucocorticoids. Serum and cerebrospinal fluid (CSF) Sema4A levels in patients with RM were elevated during the acute phase compared to those in the remission phase. Serum Sema4A was significantly increased in patients with RM than in RA controls (23.8 ng/ml versus 7.48 ng/ml, p = 0.014), although there were no significant differences in RA disease activity between the two groups. Sema4A was expressed in a few infiltrating cells and stromal tissues of the RM leptomeninges. This is the first report to demonstrate that serum and CSF Sema4A levels correlate with the disease activity of RM sine active synovitis. The expression of Sema4A in the leptomeninges may be associated with RM pathogenesis.
{"title":"Rheumatoid meningitis in the absence of active synovitis: A potential association of semaphorin 4A","authors":"Keishu Murakami ,&nbsp;Yoshiaki Nakayama ,&nbsp;Shigeru Iwata ,&nbsp;Seiji Emori ,&nbsp;Shoko Yorozu ,&nbsp;Takao Fujii ,&nbsp;Katsuichi Miyamoto","doi":"10.1016/j.jneuroim.2025.578548","DOIUrl":"10.1016/j.jneuroim.2025.578548","url":null,"abstract":"<div><div>Rheumatoid meningitis (RM) is a rare complication that can develop even in patients with inactive rheumatoid arthritis (RA). Currently, there are no reliable indicators that reflect the disease activity of RM, and its pathogenesis remains poorly understood. Herein, we presented three cases of RM without active synovitis and investigated the possible association between RM and semaphorin 4A (Sema4A). Two of the three patients with RM developed sudden onset of seizures, while one patient exhibited a slowly progressive gait disturbance and cognitive impairment. All the patients had inactive synovitis, positive anti-cyclic citrullinated peptide antibodies in the serum, high-intensity lesions on the cerebral surface on head magnetic resonance imaging, or a favorable response to glucocorticoids. Serum and cerebrospinal fluid (CSF) Sema4A levels in patients with RM were elevated during the acute phase compared to those in the remission phase. Serum Sema4A was significantly increased in patients with RM than in RA controls (23.8 ng/ml versus 7.48 ng/ml, <em>p</em> = 0.014), although there were no significant differences in RA disease activity between the two groups. Sema4A was expressed in a few infiltrating cells and stromal tissues of the RM leptomeninges. This is the first report to demonstrate that serum and CSF Sema4A levels correlate with the disease activity of RM sine active synovitis. The expression of Sema4A in the leptomeninges may be associated with RM pathogenesis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578548"},"PeriodicalIF":2.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pediatric anti-CaVα2δ autoimmune encephalitis: A case report and literature review
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.jneuroim.2025.578550
Min Zhang, Xiaomei Zhu, Lifei Yu, Zhixu Fang, Yi Wang, Linmei Zhang
Anti-voltage-gated calcium channel alpha-2/delta subunit (anti-CaVα2δ) encephalitis is a rare autoimmune encephalitis (AE), with only two cases of anti-CaVα2δ AE have been reported in the literatureto date. The clinical characteristics and prognosis of this rare AE need to beexpanded.We present the case of a 9-year-oldgirl, who initially presented with fever and lymphadenitis, which progressed to headaches, drowsiness, frequent seizures, cognitive impairment, memory loss, and involuntary movements. Brain magnetic resonance imaging revealed lesions in the bilateral external capsule. Moreover, anti-CaVα2δ antibodies were detected (1,30) 3 and 5 weeks after symptom onset. Video electroencephalography revealed slow, severely diffuse, background activity with multifocal epileptiform discharges. Although the patient was administered a combined immunotherapy consisting of intravenous immunoglobulin, intravenous methylprednisolone, and rituximab, sheexhibited persistent neurological sequelae at the last follow-up (Modified Rankin Scale score of 4; Pediatric Quality of Life Inventory score of 75). Whileour case shares similar clinical characteristics with previously reported anti-CaVα2δ AE cases, our patientwas unresponsive to immunotherapy and experienced severe neurological sequelae during follow-up. This report broadens the clinical phenotype and prognosis associated with this rare condition, providing further information and clinical insights for the management of future cases.
{"title":"Pediatric anti-CaVα2δ autoimmune encephalitis: A case report and literature review","authors":"Min Zhang,&nbsp;Xiaomei Zhu,&nbsp;Lifei Yu,&nbsp;Zhixu Fang,&nbsp;Yi Wang,&nbsp;Linmei Zhang","doi":"10.1016/j.jneuroim.2025.578550","DOIUrl":"10.1016/j.jneuroim.2025.578550","url":null,"abstract":"<div><div>Anti-voltage-gated calcium channel alpha-2/delta subunit (anti-CaVα2δ) encephalitis is a rare autoimmune encephalitis (AE), with only two cases of anti-CaVα2δ AE have been reported in the literatureto date. The clinical characteristics and prognosis of this rare AE need to beexpanded.We present the case of a 9-year-oldgirl, who initially presented with fever and lymphadenitis, which progressed to headaches, drowsiness, frequent seizures, cognitive impairment, memory loss, and involuntary movements. Brain magnetic resonance imaging revealed lesions in the bilateral external capsule. Moreover, anti-CaVα2δ antibodies were detected (1,30) 3 and 5 weeks after symptom onset. Video electroencephalography revealed slow, severely diffuse, background activity with multifocal epileptiform discharges. Although the patient was administered a combined immunotherapy consisting of intravenous immunoglobulin, intravenous methylprednisolone, and rituximab, sheexhibited persistent neurological sequelae at the last follow-up (Modified Rankin Scale score of 4; Pediatric Quality of Life Inventory score of 75). Whileour case shares similar clinical characteristics with previously reported anti-CaVα2δ AE cases, our patientwas unresponsive to immunotherapy and experienced severe neurological sequelae during follow-up. This report broadens the clinical phenotype and prognosis associated with this rare condition, providing further information and clinical insights for the management of future cases.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"401 ","pages":"Article 578550"},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and characteristics of a novel CD8αα T cell subset in a refractory myasthenia gravis patient
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.jneuroim.2025.578551
Yujia Liu , Hanxiao Sun , Yingchen Xu , Binbin Xuan , Guofang Xia , Jifeng Tang , Jinpiao Lin , Ailian Du , Huiming Sheng
Myasthenia gravis (MG) is an autoimmune disease that impairs neuromuscular transmission. Autoantibodies and cellular immunity mediate the immunopathology of MG, yet the mechanism of CD8+ T cells in this process remains elucidated. In this study, we discovered a novel subset of CD8αα+ T cells in the peripheral blood of an 18-year-old Chinese man diagnosed as MG, who has undergone thymectomy and persistent myasthenia crisis. Designated as CD161neg T cell, this subset was characterized by TCRαβ+CD8αα+PLZF+Vα7.2+ but notably lacked CD161, distinct from mucosal-associated invariant T (MAIT) cells known for high CD161. The patient exhibited unusually high levels of CD161neg T cells compared to other MG patients, which fluctuated with infections but not MG severity. RNA sequencing revealed that CD161neg T cells lacked the genes characteristic of mature MAIT cells including CCR6, CXCR6, ZBTB16, and IL18RAP, but expressed cytotoxic T cell-related genes GZMH and IFNG. This study shed new light on the heterogeneity and complexity of CD8αα+ T cells in MG patients with thymoma.
{"title":"Identification and characteristics of a novel CD8αα T cell subset in a refractory myasthenia gravis patient","authors":"Yujia Liu ,&nbsp;Hanxiao Sun ,&nbsp;Yingchen Xu ,&nbsp;Binbin Xuan ,&nbsp;Guofang Xia ,&nbsp;Jifeng Tang ,&nbsp;Jinpiao Lin ,&nbsp;Ailian Du ,&nbsp;Huiming Sheng","doi":"10.1016/j.jneuroim.2025.578551","DOIUrl":"10.1016/j.jneuroim.2025.578551","url":null,"abstract":"<div><div>Myasthenia gravis (MG) is an autoimmune disease that impairs neuromuscular transmission. Autoantibodies and cellular immunity mediate the immunopathology of MG, yet the mechanism of CD8<sup>+</sup> T cells in this process remains elucidated. In this study, we discovered a novel subset of CD8αα<sup>+</sup> T cells in the peripheral blood of an 18-year-old Chinese man diagnosed as MG, who has undergone thymectomy and persistent myasthenia crisis. Designated as CD161<sup>neg</sup> T cell, this subset was characterized by TCRαβ<sup>+</sup>CD8αα<sup>+</sup>PLZF<sup>+</sup>Vα7.2<sup>+</sup> but notably lacked CD161, distinct from mucosal-associated invariant T (MAIT) cells known for high CD161. The patient exhibited unusually high levels of CD161<sup>neg</sup> T cells compared to other MG patients, which fluctuated with infections but not MG severity. RNA sequencing revealed that CD161<sup>neg</sup> T cells lacked the genes characteristic of mature MAIT cells including <em>CCR6</em>, <em>CXCR6</em>, <em>ZBTB16</em>, and <em>IL18RAP</em>, but expressed cytotoxic T cell-related genes <em>GZMH</em> and <em>IFNG</em>. This study shed new light on the heterogeneity and complexity of CD8αα<sup>+</sup> T cells in MG patients with thymoma.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578551"},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerebellar ataxia and depression associated with anti-RhoGTPase-activating protein 26 antibody: A case report
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.jneuroim.2025.578547
Haitao Ren , Mange Liu , Min Qian, Yingmai Yang, Guan Hongzhi
Neuroimmune disorders associated with anti-RhoGTPase-activating protein 26 immunoglobulin G (IgG) autoantibodies (ARHGAP26; also termed anti-Ca) are infrequent and manifest a significant diversity in clinical presentations, including cerebellar ataxia, psychotic disorders, and cognitive impairments. This case report describes a middle-aged female who developed subacute cerebellar ataxia and depression. Detection of anti-ARHGAP26 IgG in both serum and cerebrospinal fluid (CSF) led to her diagnosis of primary autoimmune cerebellar ataxia, supported by her medical history of Sjögren's syndrome and the identification of CSF-specific oligoclonal bands. After undergoing sequential immunotherapy including corticosteroid, intravenous immunoglobulin, plasma exchange, mycophenolate mofetil and rituximab, her Scale for the Assessment and Rating of Ataxia score improved from 28.5 to 18, demonstrating partial recovery. This case highlights the necessity of considering an autoimmune etiology in patients presenting with subacute cerebellar ataxia and suggests that testing for ARHGAP26-IgG is warranted also when psychocognitive impairment is clinically evident. Early initiation of immunotherapy is important to enhance patient outcomes.
{"title":"Cerebellar ataxia and depression associated with anti-RhoGTPase-activating protein 26 antibody: A case report","authors":"Haitao Ren ,&nbsp;Mange Liu ,&nbsp;Min Qian,&nbsp;Yingmai Yang,&nbsp;Guan Hongzhi","doi":"10.1016/j.jneuroim.2025.578547","DOIUrl":"10.1016/j.jneuroim.2025.578547","url":null,"abstract":"<div><div>Neuroimmune disorders associated with anti-RhoGTPase-activating protein 26 immunoglobulin G (IgG) autoantibodies (ARHGAP26; also termed anti-Ca) are infrequent and manifest a significant diversity in clinical presentations, including cerebellar ataxia, psychotic disorders, and cognitive impairments. This case report describes a middle-aged female who developed subacute cerebellar ataxia and depression. Detection of anti-ARHGAP26 IgG in both serum and cerebrospinal fluid (CSF) led to her diagnosis of primary autoimmune cerebellar ataxia, supported by her medical history of Sjögren's syndrome and the identification of CSF-specific oligoclonal bands. After undergoing sequential immunotherapy including corticosteroid, intravenous immunoglobulin, plasma exchange, mycophenolate mofetil and rituximab, her Scale for the Assessment and Rating of Ataxia score improved from 28.5 to 18, demonstrating partial recovery. This case highlights the necessity of considering an autoimmune etiology in patients presenting with subacute cerebellar ataxia and suggests that testing for ARHGAP26-IgG is warranted also when psychocognitive impairment is clinically evident. Early initiation of immunotherapy is important to enhance patient outcomes.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578547"},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endocrine disrupting chemicals in early MS disease activity
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-07 DOI: 10.1016/j.jneuroim.2025.578546
Tzu-Ying Chuang , Brenna A. LaBarre , Osman Corbali , Brian C. Healy , Shrishti Saxena , Talia B. Feldman , Eunnindy Sanon , Taylor J. Saraceno , Tanuja Chitnis

Background and objectives

Epidemiological data shows that the prevalence of multiple sclerosis (MS) and the female-to-male sex ratio among MS patients are increasing over time. Endocrine disrupting chemicals (EDCs) are ubiquitous and increasingly recognized for effects on estrogen signaling. This study aimed to determine whether there was an association between EDC levels and disease severity in newly diagnosed, female MS patients.

Methods

This exploratory observational cohort study enrolled female patients, ages 18–60, via written informed consent from the Brigham MS Center. Enrollment criteria included diagnosis with MS within the past 5 years and completion of a questionnaire about potential EDC exposures. Exclusion criteria were intravenous steroids in the past 30 days. Collection processes and materials were designed to avoid EDC contamination. Urine samples were analyzed by NSF International (Ann Arbor, Michigan).
Primary outcome measures were MRI parameters and clinical disease activity, including multivariable analysis adjusting for MS treatment types. Spearman correlation test was used for analysis and between group comparisons were conducted with one-way ANOVA.
Results: 68 patients with MS were enrolled. In the phthalates, mEOHP was negatively correlated with T2 lesion volume over time (R value = −0.522, p-value = 0.002, Bonferroni adjusted p = 0.03). For the phenols, triclocarban was negatively associated with cheese consumption (R value = −0.402, p = 0.001, Bonferroni adjusted p = 0.012) There was no association between EDCs and disease activity or demographic factors, nor significant correlation with exposure to household plastics.

Conclusion

This exploratory study identified a negative correlation between triclocarban and cheese consumption. Longitudinally, phthalate metabolite mEOHP was negatively correlated with T2 lesion volume over time. Exposure to EDCs may affect the early disease course in MS, and expansion of research efforts is warranted.
{"title":"Endocrine disrupting chemicals in early MS disease activity","authors":"Tzu-Ying Chuang ,&nbsp;Brenna A. LaBarre ,&nbsp;Osman Corbali ,&nbsp;Brian C. Healy ,&nbsp;Shrishti Saxena ,&nbsp;Talia B. Feldman ,&nbsp;Eunnindy Sanon ,&nbsp;Taylor J. Saraceno ,&nbsp;Tanuja Chitnis","doi":"10.1016/j.jneuroim.2025.578546","DOIUrl":"10.1016/j.jneuroim.2025.578546","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Epidemiological data shows that the prevalence of multiple sclerosis (MS) and the female-to-male sex ratio among MS patients are increasing over time. Endocrine disrupting chemicals (EDCs) are ubiquitous and increasingly recognized for effects on estrogen signaling. This study aimed to determine whether there was an association between EDC levels and disease severity in newly diagnosed, female MS patients.</div></div><div><h3>Methods</h3><div>This exploratory observational cohort study enrolled female patients, ages 18–60, via written informed consent from the Brigham MS Center. Enrollment criteria included diagnosis with MS within the past 5 years and completion of a questionnaire about potential EDC exposures. Exclusion criteria were intravenous steroids in the past 30 days. Collection processes and materials were designed to avoid EDC contamination. Urine samples were analyzed by NSF International (Ann Arbor, Michigan).</div><div>Primary outcome measures were MRI parameters and clinical disease activity, including multivariable analysis adjusting for MS treatment types. Spearman correlation test was used for analysis and between group comparisons were conducted with one-way ANOVA.</div><div>Results: 68 patients with MS were enrolled. In the phthalates, mEOHP was negatively correlated with T2 lesion volume over time (R value = −0.522, <em>p</em>-value = 0.002, Bonferroni adjusted <em>p</em> = 0.03). For the phenols, triclocarban was negatively associated with cheese consumption (R value = −0.402, <em>p</em> = 0.001, Bonferroni adjusted <em>p</em> = 0.012) There was no association between EDCs and disease activity or demographic factors, nor significant correlation with exposure to household plastics.</div></div><div><h3>Conclusion</h3><div>This exploratory study identified a negative correlation between triclocarban and cheese consumption. Longitudinally, phthalate metabolite mEOHP was negatively correlated with T2 lesion volume over time. Exposure to EDCs may affect the early disease course in MS, and expansion of research efforts is warranted.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578546"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain network alteration was associated with ‘no evidence of disease activity’ status in patients with relapsing-remitting multiple sclerosis
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-07 DOI: 10.1016/j.jneuroim.2025.578549
Zichun Yan , Xiaolin Yang , Bing Lin , Qiyuan Zhu , Zhuowei Shi , Yaou Liu , Shuang Ding , Xiaohua Wang , Zhengyu Chen , Xiaoya Chen , Yuhui Xu , Yang Tang , Jinzhou Feng , Yongmei Li

Background

The associations between the monthly rate of topological property change (mrTPC) in the structural and functional connectivity network (SCN, FCN) and achieving no evidence of disease activity (NEDA) in relapsing-remitting multiple sclerosis (RRMS) patients taking oral disease-modifying therapies (DMTs) remain insufficiently explored.

Methods

This was a retrospective study conducted with RRMS patients treated with oral DMTs or untreated between January 2019 and June 2023. All participants underwent baseline and follow-up clinical evaluations and MRI scans. Initially, NEDA statuses of all participants were assessed. Then, the mrTPCs from SCN and FCN were calculated. Finally, the baseline characteristics and mrTPCs were inserted into logistic regression models to explore their associations with achieving NEDA status.

Results

A total of 58 RRMS patients were included, with 46 in the treated group and 12 in the untreated group. A greater percentage of treated RRMS patients achieved NEDA3+ (60.87 % vs. 25.00 %) or NEDA4+ (21.74 % vs. 8.33 %) statuses. Patients with oral DMTs (P = 0.032) and lower contrast-enhancing lesions (CELs) count (P = 0.009) were more likely to achieve NEDA3+ status. Nomograms based on the mrTPCs revealed SCN_NLe_SMA.R (P = 0.042) and FCN_NLe_PCL.L (P = 0.050) were significant for the NEDA3 or NEDA 4 model. Both the above models performed well (AUC: 0.756 and 0.722, respectively).

Conclusions

Specifically altered mrTPC was linked to NEDA status in RRMS patients on oral DMTs. Although the specific mechanisms for each NEDA status may differ and need further investigation, these findings can help clinicians personalize RRMS treatment and monitoring.
{"title":"Brain network alteration was associated with ‘no evidence of disease activity’ status in patients with relapsing-remitting multiple sclerosis","authors":"Zichun Yan ,&nbsp;Xiaolin Yang ,&nbsp;Bing Lin ,&nbsp;Qiyuan Zhu ,&nbsp;Zhuowei Shi ,&nbsp;Yaou Liu ,&nbsp;Shuang Ding ,&nbsp;Xiaohua Wang ,&nbsp;Zhengyu Chen ,&nbsp;Xiaoya Chen ,&nbsp;Yuhui Xu ,&nbsp;Yang Tang ,&nbsp;Jinzhou Feng ,&nbsp;Yongmei Li","doi":"10.1016/j.jneuroim.2025.578549","DOIUrl":"10.1016/j.jneuroim.2025.578549","url":null,"abstract":"<div><h3>Background</h3><div>The associations between the monthly rate of topological property change (mrTPC) in the structural and functional connectivity network (SCN, FCN) and achieving no evidence of disease activity (NEDA) in relapsing-remitting multiple sclerosis (RRMS) patients taking oral disease-modifying therapies (DMTs) remain insufficiently explored.</div></div><div><h3>Methods</h3><div>This was a retrospective study conducted with RRMS patients treated with oral DMTs or untreated between January 2019 and June 2023. All participants underwent baseline and follow-up clinical evaluations and MRI scans. Initially, NEDA statuses of all participants were assessed. Then, the mrTPCs from SCN and FCN were calculated. Finally, the baseline characteristics and mrTPCs were inserted into logistic regression models to explore their associations with achieving NEDA status.</div></div><div><h3>Results</h3><div>A total of 58 RRMS patients were included, with 46 in the treated group and 12 in the untreated group. A greater percentage of treated RRMS patients achieved NEDA3+ (60.87 % vs. 25.00 %) or NEDA4+ (21.74 % vs. 8.33 %) statuses. Patients with oral DMTs (<em>P</em> = 0.032) and lower contrast-enhancing lesions (CELs) count (<em>P</em> = 0.009) were more likely to achieve NEDA3+ status. Nomograms based on the mrTPCs revealed SCN_NLe_SMA.R (<em>P</em> = 0.042) and FCN_NLe_PCL.L (<em>P</em> = 0.050) were significant for the NEDA3 or NEDA 4 model. Both the above models performed well (AUC: 0.756 and 0.722, respectively).</div></div><div><h3>Conclusions</h3><div>Specifically altered mrTPC was linked to NEDA status in RRMS patients on oral DMTs. Although the specific mechanisms for each NEDA status may differ and need further investigation, these findings can help clinicians personalize RRMS treatment and monitoring.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578549"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute corticosteroid-responsive post-infection myositis in adults
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-03 DOI: 10.1016/j.jneuroim.2025.578543
Yirong Yang , Min Zhu , Yusen Qiu , Dandan Tan , Si Luo , Menghua Li , Yanyan Yu , Meihong Zhou , Daojun Hong
Functional disability myalgia is a common condition that frequently leads to significant disability, but its diagnosis is challenging because of its diverse etiologies. While hereditary myalgia has been wells tudied, infection-related myalgia, particularly post-infection forms, remains underrecognized. In this study, six adult patients with severe post-infection myalgia were described. The mean age of onset for these patients was 63.2 ± 16.2 years. All patients experienced myalgia and muscle weakness in the proximal muscles of the lower limbs, which occurred 1–4 weeks after the recovery from symptoms of suspected viral infection, resulting in a significant functional disability. Laboratory tests revealed that creatine kinase levels were not elevated, yet increases in C-reactive protein, erythrocyte sedimentation rate, and interleukin-6 levels were observed. Muscle MRI demonstrated significant edema in the lower limb muscles of 5 patients, while muscle biopsy indicated mild inflammatory myopathy changes in 5 patients. Severe muscle pain were unresponsive to nonsteroidal anti-inflammatory drugs but showed a significant response to steroids, and most patients had favorable prognoses. These clinical features differed from previously documented cases of post-infection myositis, suggesting a distinct subset of infection-related myalgia. Our findings highlighted the importance of recognizing this condition in adults and suggested the need for broader diagnostic criteria to better classify infection-related myopathies.
{"title":"Acute corticosteroid-responsive post-infection myositis in adults","authors":"Yirong Yang ,&nbsp;Min Zhu ,&nbsp;Yusen Qiu ,&nbsp;Dandan Tan ,&nbsp;Si Luo ,&nbsp;Menghua Li ,&nbsp;Yanyan Yu ,&nbsp;Meihong Zhou ,&nbsp;Daojun Hong","doi":"10.1016/j.jneuroim.2025.578543","DOIUrl":"10.1016/j.jneuroim.2025.578543","url":null,"abstract":"<div><div>Functional disability myalgia is a common condition that frequently leads to significant disability, but its diagnosis is challenging because of its diverse etiologies. While hereditary myalgia has been wells tudied, infection-related myalgia, particularly post-infection forms, remains underrecognized. In this study, six adult patients with severe post-infection myalgia were described. The mean age of onset for these patients was 63.2 ± 16.2 years. All patients experienced myalgia and muscle weakness in the proximal muscles of the lower limbs, which occurred 1–4 weeks after the recovery from symptoms of suspected viral infection, resulting in a significant functional disability. Laboratory tests revealed that creatine kinase levels were not elevated, yet increases in C-reactive protein, erythrocyte sedimentation rate, and interleukin-6 levels were observed. Muscle MRI demonstrated significant edema in the lower limb muscles of 5 patients, while muscle biopsy indicated mild inflammatory myopathy changes in 5 patients. Severe muscle pain were unresponsive to nonsteroidal anti-inflammatory drugs but showed a significant response to steroids, and most patients had favorable prognoses. These clinical features differed from previously documented cases of post-infection myositis, suggesting a distinct subset of infection-related myalgia. Our findings highlighted the importance of recognizing this condition in adults and suggested the need for broader diagnostic criteria to better classify infection-related myopathies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578543"},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143305168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical and neuroimaging findings of patients with glial fibrillary acidic protein-immunoglobulin G-like anti-astrocytic antibodies in cerebrospinal fluid
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-03 DOI: 10.1016/j.jneuroim.2025.578545
Akio Kimura, Akira Takekoshi, Takayoshi Shimohata
We report the clinical and neuroimaging findings of patients with glial fibrillary acidic protein (GFAP)-immunoglobulin G (IgG)-like anti-astrocytic antibodies in their cerebrospinal fluid. We identified 28 patients whose IgG reacted with astrocytes in a tissue-based assay but did not react with GFAPα in a cell-based assay. Many patients presented with fever and/or headache, followed by consciousness disturbance, meningeal irritation, hyperreflexia, and urinary disturbance. Three patients each showed perivascular radial gadolinium enhancement or longitudinally extensive spinal cord lesions on magnetic resonance imaging. Thirteen of 14 patients responded to the immunotherapies. We suggest that these patients exhibited immunotherapy-responsive inflammatory neurological disorders with cerebrospinal fluid GFAP-IgG-like anti-astrocytic antibodies.
{"title":"Clinical and neuroimaging findings of patients with glial fibrillary acidic protein-immunoglobulin G-like anti-astrocytic antibodies in cerebrospinal fluid","authors":"Akio Kimura,&nbsp;Akira Takekoshi,&nbsp;Takayoshi Shimohata","doi":"10.1016/j.jneuroim.2025.578545","DOIUrl":"10.1016/j.jneuroim.2025.578545","url":null,"abstract":"<div><div>We report the clinical and neuroimaging findings of patients with glial fibrillary acidic protein (GFAP)-immunoglobulin G (IgG)-like anti-astrocytic antibodies in their cerebrospinal fluid. We identified 28 patients whose IgG reacted with astrocytes in a tissue-based assay but did not react with GFAPα in a cell-based assay. Many patients presented with fever and/or headache, followed by consciousness disturbance, meningeal irritation, hyperreflexia, and urinary disturbance. Three patients each showed perivascular radial gadolinium enhancement or longitudinally extensive spinal cord lesions on magnetic resonance imaging. Thirteen of 14 patients responded to the immunotherapies. We suggest that these patients exhibited immunotherapy-responsive inflammatory neurological disorders with cerebrospinal fluid GFAP-IgG-like anti-astrocytic antibodies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578545"},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143305169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MicroRNA signatures of CD4+ T cell subsets in healthy and multiple sclerosis subjects determined by small RNA-sequencing
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jneuroim.2025.578531
Slobodan Culina , Pierre-Henri Commère , Elodie Turc , Axel Jouy , Sandra Pellegrini , Thomas Roux , Milena Hasan , Marc Monot , Frédérique Michel
Diverse CD4+ T cell subsets with specialized functions operate at different phases of the immune response. Among these are phenotypically and functionally characterized naïve, central memory (CM), effector memory (EM), and regulatory (Treg) cells. Using small RNA-sequencing, we have profiled miRNAs in these cell subsets from healthy subjects and untreated patients with relapsing-remitting multiple sclerosis (RRMS). MiRNA genomic clustering and abundance were also investigated. From the 60 most differentially expressed miRNAs, broad and highly selective core signatures were determined for naïve and memory cells at homeostasis, while miR-146a-5p was strongly upregulated in Treg cells. In line with other studies, a 5-miRNA core was identified for naïve cells (miR-125b-5p, miR-99a-5p, miR-365a-3p, miR-365b-3p, miR-193b-3p). In memory cells, a number of identical miRNAs were more expressed in EM than CM cells, supporting the progressive T cell differentiation model. This was particularly the case for an 8-miRNA core (members from miR-23a∼27a∼24–2, miR-23b∼27b∼24–1, miR-221∼222 clusters, miR-22-3p, miR-181c-5p) and for the large ChrXq27.3 miR-506∼514 cluster. Interestingly, most of these miRNAs were reported to negatively regulate cell proliferation and survival. Finally, we found that the miRNA core signatures of naïve and memory CD4+ T cells were conserved in RRMS patients. Only few miRNAs were quantitatively modified and, among these, miR-1248 was validated to be downregulated in EM cells. Overall, this study expands and provides novel insights into miRNA profiling of CD4+ T cell subsets that may be useful for further investigations.
{"title":"MicroRNA signatures of CD4+ T cell subsets in healthy and multiple sclerosis subjects determined by small RNA-sequencing","authors":"Slobodan Culina ,&nbsp;Pierre-Henri Commère ,&nbsp;Elodie Turc ,&nbsp;Axel Jouy ,&nbsp;Sandra Pellegrini ,&nbsp;Thomas Roux ,&nbsp;Milena Hasan ,&nbsp;Marc Monot ,&nbsp;Frédérique Michel","doi":"10.1016/j.jneuroim.2025.578531","DOIUrl":"10.1016/j.jneuroim.2025.578531","url":null,"abstract":"<div><div>Diverse CD4<sup>+</sup> T cell subsets with specialized functions operate at different phases of the immune response. Among these are phenotypically and functionally characterized naïve, central memory (CM), effector memory (EM), and regulatory (Treg) cells. Using small RNA-sequencing, we have profiled miRNAs in these cell subsets from healthy subjects and untreated patients with relapsing-remitting multiple sclerosis (RRMS). MiRNA genomic clustering and abundance were also investigated. From the 60 most differentially expressed miRNAs, broad and highly selective core signatures were determined for naïve and memory cells at homeostasis, while miR-146a-5p was strongly upregulated in Treg cells. In line with other studies, a 5-miRNA core was identified for naïve cells (miR-125b-5p, miR-99a-5p, miR-365a-3p, miR-365b-3p, miR-193b-3p). In memory cells, a number of identical miRNAs were more expressed in EM than CM cells, supporting the progressive T cell differentiation model. This was particularly the case for an 8-miRNA core (members from miR-23a∼27a∼24–2, miR-23b∼27b∼24–1, miR-221∼222 clusters, miR-22-3p, miR-181c-5p) and for the large ChrXq27.3 miR-506∼514 cluster. Interestingly, most of these miRNAs were reported to negatively regulate cell proliferation and survival. Finally, we found that the miRNA core signatures of naïve and memory CD4<sup>+</sup> T cells were conserved in RRMS patients. Only few miRNAs were quantitatively modified and, among these, miR-1248 was validated to be downregulated in EM cells. Overall, this study expands and provides novel insights into miRNA profiling of CD4<sup>+</sup> T cell subsets that may be useful for further investigations.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"401 ","pages":"Article 578531"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of neuroimmunology
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