Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation
BackgroundAlthough the diagnosis is mainly dependent on the detection of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody titers in CSF and disease severity and prognosis in anti-NMDAR enceph...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971659/full |
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| author | Yuchen Li Keyu Yang Fang Zhang Jing Wang Huijun Shen Miaomiao Liu Junhong Guo Jie Wang |
| author_facet | Yuchen Li Keyu Yang Fang Zhang Jing Wang Huijun Shen Miaomiao Liu Junhong Guo Jie Wang |
| author_sort | Yuchen Li |
| collection | DOAJ |
| description | BackgroundAlthough the diagnosis is mainly dependent on the detection of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody titers in CSF and disease severity and prognosis in anti-NMDAR encephalitis patients. Here, we aimed to extensively identify CSF biomarkers related to the occurrence, development, and prognosis of anti-NMDAR encephalitis using a high-throughput proteomic approach.MethodsA CSF cytokine antibody array containing 80 cytokines and inflammatory mediators related to immune and inflammatory responses was applied to identify biomarker candidates in individual CSF samples from a well-characterized cohort comprising patients with anti-NMDAR encephalitis (n = 6) and controls (n = 6). Validation and specific detection were performed in an extended cohort consisting of anti-NMDAR encephalitis patients (n = 13), controls (n = 13), and viral encephalitis (n = 13) by enzyme-linked immunosorbent assay (ELISA). Additionally, the levels of some inflammatory proteins in three groups in cohort 2 reported in previous literatures that may be involved in the development of anti-NMDAR encephalitis were also tested by ELISA. Correlations between candidate biomarkers and clinical characteristics of anti-NMDAR encephalitis patients were analyzed.ResultsThree differentially expressed cytokines and inflammatory mediators were screened from the 80-cytokine array in cohort 1. Functional enrichment analysis results suggested that these differentially expressed proteins were related to autophagy, immune/inflammatory responses, cell death, and other processes. In cohort 2, the elevations of cellular inhibitor of apoptosis protein-1 (cIAP-1), macrophage colony-stimulating factor (MCSF), CXC chemokine ligand 13 (CXCL13), and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in anti-NMDAR encephalitis were validated by ELISA. Linear regression revealed that the levels of CSF CXCL13 and cIAP-1 were positively correlated with the highest modified Rankin scale (mRS) score in the acute phase (p < 0.05). The level of cIAP-1 was positively correlated with the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score (p < 0.05).ConclusionThese biomarkers show promising functions to evaluate severity or prognosis of anti-NMDAR encephalitis. The biological processes of immune/inflammatory responses, altered levels of autophagy, and the tumor necrosis factor (TNF) signal pathway may be involved in the pathophysiology of anti-NMDAR encephalitis to some extent. |
| first_indexed | 2024-04-13T18:12:42Z |
| format | Article |
| id | doaj.art-0147561984f74dd8909303b71c032aec |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T18:12:42Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-0147561984f74dd8909303b71c032aec2022-12-22T02:35:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.971659971659Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigationYuchen Li0Keyu Yang1Fang Zhang2Jing Wang3Huijun Shen4Miaomiao Liu5Junhong Guo6Jie Wang7Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Critical Care Medicine, Aerospace Center Hospital, Beijing, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Neurology, First Hospital of Shanxi Medical University, Taiyuan, ChinaBackgroundAlthough the diagnosis is mainly dependent on the detection of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody titers in CSF and disease severity and prognosis in anti-NMDAR encephalitis patients. Here, we aimed to extensively identify CSF biomarkers related to the occurrence, development, and prognosis of anti-NMDAR encephalitis using a high-throughput proteomic approach.MethodsA CSF cytokine antibody array containing 80 cytokines and inflammatory mediators related to immune and inflammatory responses was applied to identify biomarker candidates in individual CSF samples from a well-characterized cohort comprising patients with anti-NMDAR encephalitis (n = 6) and controls (n = 6). Validation and specific detection were performed in an extended cohort consisting of anti-NMDAR encephalitis patients (n = 13), controls (n = 13), and viral encephalitis (n = 13) by enzyme-linked immunosorbent assay (ELISA). Additionally, the levels of some inflammatory proteins in three groups in cohort 2 reported in previous literatures that may be involved in the development of anti-NMDAR encephalitis were also tested by ELISA. Correlations between candidate biomarkers and clinical characteristics of anti-NMDAR encephalitis patients were analyzed.ResultsThree differentially expressed cytokines and inflammatory mediators were screened from the 80-cytokine array in cohort 1. Functional enrichment analysis results suggested that these differentially expressed proteins were related to autophagy, immune/inflammatory responses, cell death, and other processes. In cohort 2, the elevations of cellular inhibitor of apoptosis protein-1 (cIAP-1), macrophage colony-stimulating factor (MCSF), CXC chemokine ligand 13 (CXCL13), and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in anti-NMDAR encephalitis were validated by ELISA. Linear regression revealed that the levels of CSF CXCL13 and cIAP-1 were positively correlated with the highest modified Rankin scale (mRS) score in the acute phase (p < 0.05). The level of cIAP-1 was positively correlated with the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score (p < 0.05).ConclusionThese biomarkers show promising functions to evaluate severity or prognosis of anti-NMDAR encephalitis. The biological processes of immune/inflammatory responses, altered levels of autophagy, and the tumor necrosis factor (TNF) signal pathway may be involved in the pathophysiology of anti-NMDAR encephalitis to some extent.https://www.frontiersin.org/articles/10.3389/fimmu.2022.971659/fullanti-N-methyl-D-aspartate receptor encephalitiscytokinesbiomarkerscerebrospinal fluidproteomics |
| spellingShingle | Yuchen Li Keyu Yang Fang Zhang Jing Wang Huijun Shen Miaomiao Liu Junhong Guo Jie Wang Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation Frontiers in Immunology anti-N-methyl-D-aspartate receptor encephalitis cytokines biomarkers cerebrospinal fluid proteomics |
| title | Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation |
| title_full | Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation |
| title_fullStr | Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation |
| title_full_unstemmed | Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation |
| title_short | Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation |
| title_sort | identification of cerebrospinal fluid biomarker candidates for anti n methyl d aspartate receptor encephalitis high throughput proteomic investigation |
| topic | anti-N-methyl-D-aspartate receptor encephalitis cytokines biomarkers cerebrospinal fluid proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971659/full |
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