Jan D Lunemann, Harald Hegen, Luisa María Villar, Konrad Rejdak, Augusto Sao-Aviles, Pere Carbonell-Mirabent, Jaume Sastre-Garriga, Neus Mongay-Ochoa, Klaus Berek, Sergio Martínez-Yélamos, Francisco Pérez-Miralles, Ahmed Abdelhak, Franziska Bachhuber, Hayrettin Tumani, Jan N Lycke, Igal Rosenstein, Roberto Alvarez-Lafuente, Tamara Castillo-Trivino, David Otaegui, Sara Llufriu, Yolanda Blanco, Antonio J Sánchez López, Juan Antonio Garcia Merino, Nicolas Fissolo, Lucia Gutierrez, Javier Villacieros-Álvarez, Enric Monreal, Adrián Valls-Carbó, Heinz Wiendl, Xavier Montalban, Manuel Comabella
{"title":"补体因素与原发性进展型多发性硬化症残疾进展的关系","authors":"Jan D Lunemann, Harald Hegen, Luisa María Villar, Konrad Rejdak, Augusto Sao-Aviles, Pere Carbonell-Mirabent, Jaume Sastre-Garriga, Neus Mongay-Ochoa, Klaus Berek, Sergio Martínez-Yélamos, Francisco Pérez-Miralles, Ahmed Abdelhak, Franziska Bachhuber, Hayrettin Tumani, Jan N Lycke, Igal Rosenstein, Roberto Alvarez-Lafuente, Tamara Castillo-Trivino, David Otaegui, Sara Llufriu, Yolanda Blanco, Antonio J Sánchez López, Juan Antonio Garcia Merino, Nicolas Fissolo, Lucia Gutierrez, Javier Villacieros-Álvarez, Enric Monreal, Adrián Valls-Carbó, Heinz Wiendl, Xavier Montalban, Manuel Comabella","doi":"10.1212/NXI.0000000000200270","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).</p><p><strong>Methods: </strong>Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).</p><p><strong>Results: </strong>In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; <i>p</i> = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; <i>p</i> = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; <i>p</i> = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; <i>p</i> = 0.025).</p><p><strong>Discussion: </strong>Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200270"},"PeriodicalIF":7.8000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226316/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.\",\"authors\":\"Jan D Lunemann, Harald Hegen, Luisa María Villar, Konrad Rejdak, Augusto Sao-Aviles, Pere Carbonell-Mirabent, Jaume Sastre-Garriga, Neus Mongay-Ochoa, Klaus Berek, Sergio Martínez-Yélamos, Francisco Pérez-Miralles, Ahmed Abdelhak, Franziska Bachhuber, Hayrettin Tumani, Jan N Lycke, Igal Rosenstein, Roberto Alvarez-Lafuente, Tamara Castillo-Trivino, David Otaegui, Sara Llufriu, Yolanda Blanco, Antonio J Sánchez López, Juan Antonio Garcia Merino, Nicolas Fissolo, Lucia Gutierrez, Javier Villacieros-Álvarez, Enric Monreal, Adrián Valls-Carbó, Heinz Wiendl, Xavier Montalban, Manuel Comabella\",\"doi\":\"10.1212/NXI.0000000000200270\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).</p><p><strong>Methods: </strong>Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).</p><p><strong>Results: </strong>In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; <i>p</i> = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; <i>p</i> = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; <i>p</i> = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; <i>p</i> = 0.025).</p><p><strong>Discussion: </strong>Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.</p>\",\"PeriodicalId\":19472,\"journal\":{\"name\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"volume\":\"11 4\",\"pages\":\"e200270\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226316/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200270\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200270","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.
Background and objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).
Methods: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).
Results: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025).
Discussion: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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