Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights
Objective To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication. Methods In this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐...
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Veröffentlicht in: | Annals of neurology 2024-10, Vol.96 (4), p.704-714 |
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creator | Mangioris, Georgios Pittock, Sean J. Yang, Binxia Fryer, James P. Harmsen, William S. Dubey, Divyanshu Flanagan, Eoin P. Lopez‐Chiriboga, Sebastian A. McKeon, Andrew Mills, John R. Vodopivec, Ivana Tobin, W. Oliver Toledano, Michel Aksamit, Allen J. Zekeridou, Anastasia |
description | Objective
To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.
Methods
In this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17A, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and tumor necrosis factor [TNF]‐alpha) in a multiplexed automated immunoassay system (ELLA; Bio‐Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011–02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin‐4 immunoglobulin G positivity, non‐inflammatory disorders, and healthy individuals were used as controls.
Results
A total of 32 NS patients (59% women; median age, 59 years [19–81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin‐4 immunoglobulin G positive, and 34 patients with non‐inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL‐2, IL‐6, IL‐10, IL‐13, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and TNF‐alpha levels were significantly higher in NS patients compared with non‐inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL‐6, CXCL9, CXCL10, GM‐CSF, interferon‐gamma, and TNF‐alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL‐6, IL‐10, IL‐13, CXCL9, CXL10, GM‐CSF, and TNF‐alpha associated with measures of disease activity.
Interpretation
NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B‐cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704–714 |
doi_str_mv | 10.1002/ana.27024 |
format | Article |
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To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.
Methods
In this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17A, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and tumor necrosis factor [TNF]‐alpha) in a multiplexed automated immunoassay system (ELLA; Bio‐Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011–02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin‐4 immunoglobulin G positivity, non‐inflammatory disorders, and healthy individuals were used as controls.
Results
A total of 32 NS patients (59% women; median age, 59 years [19–81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin‐4 immunoglobulin G positive, and 34 patients with non‐inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL‐2, IL‐6, IL‐10, IL‐13, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and TNF‐alpha levels were significantly higher in NS patients compared with non‐inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL‐6, CXCL9, CXCL10, GM‐CSF, interferon‐gamma, and TNF‐alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL‐6, IL‐10, IL‐13, CXCL9, CXL10, GM‐CSF, and TNF‐alpha associated with measures of disease activity.
Interpretation
NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B‐cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704–714</description><identifier>ISSN: 0364-5134</identifier><identifier>ISSN: 1531-8249</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.27024</identifier><identifier>PMID: 39031103</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Aquaporins ; Autoimmune diseases ; Biomarkers - blood ; Biomarkers - cerebrospinal fluid ; BLyS protein ; Case-Control Studies ; Central nervous system ; Central Nervous System Diseases - blood ; Central Nervous System Diseases - cerebrospinal fluid ; Central Nervous System Diseases - diagnosis ; Cerebrospinal fluid ; Chemokines ; Chemokines - blood ; Chemokines - cerebrospinal fluid ; CXCL10 protein ; CXCL13 protein ; Cytokines ; Cytokines - blood ; Cytokines - cerebrospinal fluid ; Diagnosis ; Diagnosis, Differential ; Differential diagnosis ; Disorders ; Female ; Gadolinium ; Helper cells ; Humans ; IgG antibody ; Immunoassay ; Immunoglobulin G ; Immunoglobulins ; Inflammatory diseases ; Interferon ; Interleukin 6 ; Lymphocytes ; Lymphocytes T ; Lymphoma ; Macrophages ; Male ; Middle Aged ; Multiple sclerosis ; Nervous system ; Nervous system diseases ; Pleocytosis ; Sarcoidosis ; Sarcoidosis - blood ; Sarcoidosis - cerebrospinal fluid ; Sarcoidosis - diagnosis ; Tumor necrosis factor ; Tumor necrosis factor-TNF</subject><ispartof>Annals of neurology, 2024-10, Vol.96 (4), p.704-714</ispartof><rights>2024 American Neurological Association.</rights><rights>2024 American Neurological Association</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2434-4aa8f092c8711f4557b1390c1beaf472a6079108c6aa27e3182c3b586d2991c93</cites><orcidid>0000-0001-5653-5600 ; 0000-0002-6661-2910 ; 0000-0002-1960-9065 ; 0000-0001-5051-1739 ; 0000-0001-6865-9045 ; 0000-0001-6856-8143 ; 0000-0002-9046-7880 ; 0000-0002-6140-5584 ; 0000-0002-8141-2394</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.27024$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.27024$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39031103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mangioris, Georgios</creatorcontrib><creatorcontrib>Pittock, Sean J.</creatorcontrib><creatorcontrib>Yang, Binxia</creatorcontrib><creatorcontrib>Fryer, James P.</creatorcontrib><creatorcontrib>Harmsen, William S.</creatorcontrib><creatorcontrib>Dubey, Divyanshu</creatorcontrib><creatorcontrib>Flanagan, Eoin P.</creatorcontrib><creatorcontrib>Lopez‐Chiriboga, Sebastian A.</creatorcontrib><creatorcontrib>McKeon, Andrew</creatorcontrib><creatorcontrib>Mills, John R.</creatorcontrib><creatorcontrib>Vodopivec, Ivana</creatorcontrib><creatorcontrib>Tobin, W. Oliver</creatorcontrib><creatorcontrib>Toledano, Michel</creatorcontrib><creatorcontrib>Aksamit, Allen J.</creatorcontrib><creatorcontrib>Zekeridou, Anastasia</creatorcontrib><title>Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.
Methods
In this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17A, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and tumor necrosis factor [TNF]‐alpha) in a multiplexed automated immunoassay system (ELLA; Bio‐Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011–02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin‐4 immunoglobulin G positivity, non‐inflammatory disorders, and healthy individuals were used as controls.
Results
A total of 32 NS patients (59% women; median age, 59 years [19–81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin‐4 immunoglobulin G positive, and 34 patients with non‐inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL‐2, IL‐6, IL‐10, IL‐13, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and TNF‐alpha levels were significantly higher in NS patients compared with non‐inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL‐6, CXCL9, CXCL10, GM‐CSF, interferon‐gamma, and TNF‐alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL‐6, IL‐10, IL‐13, CXCL9, CXL10, GM‐CSF, and TNF‐alpha associated with measures of disease activity.
Interpretation
NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B‐cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704–714</description><subject>Adult</subject><subject>Aged</subject><subject>Aquaporins</subject><subject>Autoimmune diseases</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>BLyS protein</subject><subject>Case-Control Studies</subject><subject>Central nervous system</subject><subject>Central Nervous System Diseases - blood</subject><subject>Central Nervous System Diseases - cerebrospinal fluid</subject><subject>Central Nervous System Diseases - diagnosis</subject><subject>Cerebrospinal fluid</subject><subject>Chemokines</subject><subject>Chemokines - blood</subject><subject>Chemokines - cerebrospinal fluid</subject><subject>CXCL10 protein</subject><subject>CXCL13 protein</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - cerebrospinal fluid</subject><subject>Diagnosis</subject><subject>Diagnosis, Differential</subject><subject>Differential diagnosis</subject><subject>Disorders</subject><subject>Female</subject><subject>Gadolinium</subject><subject>Helper cells</subject><subject>Humans</subject><subject>IgG antibody</subject><subject>Immunoassay</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins</subject><subject>Inflammatory diseases</subject><subject>Interferon</subject><subject>Interleukin 6</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Macrophages</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Nervous system</subject><subject>Nervous system diseases</subject><subject>Pleocytosis</subject><subject>Sarcoidosis</subject><subject>Sarcoidosis - blood</subject><subject>Sarcoidosis - cerebrospinal fluid</subject><subject>Sarcoidosis - diagnosis</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-TNF</subject><issn>0364-5134</issn><issn>1531-8249</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1P3DAQhq2qCLbAoX-gitRLewjM2M6He1uFAishQALOkeN1dk0Te7GToj33j2MI9IDEyRrrmUea9yXkK8IRAtBjaeURLYDyT2SGGcO0pFx8JjNgOU8zZHyPfAnhHgBEjrBL9pgAhghsRv5V2uvGu7AxVnbJaTeaZVJtB_fHWJ1IG4e17qfp2rvWdDokxiaVtoOPC5fa_3VjSG62YdB9ciO9cmbpggm_khMjV9aFwagX0aLvR-s2cli7zq3i58IGs1oP4YDstLIL-vD13Sd3p79vq_P04upsUc0vUkU54ymXsmxBUFUWiC3PsqLBeIjCRsuWF1TmUAiEUuVS0kIzLKliTVbmSyoEKsH2yY_Ju_HuYdRhqHsTlO46aXW8oWZQUpEJRllEv79D793oY0KRQsryHAR_pn5OlIoBBq_beuNNL_22Rqifm6ljM_VLM5H99mocm14v_5NvVUTgeAIeY8bbj031_HI-KZ8Ans2Xzw</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>Mangioris, Georgios</creator><creator>Pittock, Sean J.</creator><creator>Yang, Binxia</creator><creator>Fryer, James P.</creator><creator>Harmsen, William S.</creator><creator>Dubey, Divyanshu</creator><creator>Flanagan, Eoin P.</creator><creator>Lopez‐Chiriboga, Sebastian A.</creator><creator>McKeon, Andrew</creator><creator>Mills, John R.</creator><creator>Vodopivec, Ivana</creator><creator>Tobin, W. Oliver</creator><creator>Toledano, Michel</creator><creator>Aksamit, Allen J.</creator><creator>Zekeridou, Anastasia</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5653-5600</orcidid><orcidid>https://orcid.org/0000-0002-6661-2910</orcidid><orcidid>https://orcid.org/0000-0002-1960-9065</orcidid><orcidid>https://orcid.org/0000-0001-5051-1739</orcidid><orcidid>https://orcid.org/0000-0001-6865-9045</orcidid><orcidid>https://orcid.org/0000-0001-6856-8143</orcidid><orcidid>https://orcid.org/0000-0002-9046-7880</orcidid><orcidid>https://orcid.org/0000-0002-6140-5584</orcidid><orcidid>https://orcid.org/0000-0002-8141-2394</orcidid></search><sort><creationdate>202410</creationdate><title>Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights</title><author>Mangioris, Georgios ; Pittock, Sean J. ; Yang, Binxia ; Fryer, James P. ; Harmsen, William S. ; Dubey, Divyanshu ; Flanagan, Eoin P. ; Lopez‐Chiriboga, Sebastian A. ; McKeon, Andrew ; Mills, John R. ; Vodopivec, Ivana ; Tobin, W. Oliver ; Toledano, Michel ; Aksamit, Allen J. ; Zekeridou, Anastasia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2434-4aa8f092c8711f4557b1390c1beaf472a6079108c6aa27e3182c3b586d2991c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aquaporins</topic><topic>Autoimmune diseases</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>BLyS protein</topic><topic>Case-Control Studies</topic><topic>Central nervous system</topic><topic>Central Nervous System Diseases - blood</topic><topic>Central Nervous System Diseases - cerebrospinal fluid</topic><topic>Central Nervous System Diseases - diagnosis</topic><topic>Cerebrospinal fluid</topic><topic>Chemokines</topic><topic>Chemokines - blood</topic><topic>Chemokines - cerebrospinal fluid</topic><topic>CXCL10 protein</topic><topic>CXCL13 protein</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - cerebrospinal fluid</topic><topic>Diagnosis</topic><topic>Diagnosis, Differential</topic><topic>Differential diagnosis</topic><topic>Disorders</topic><topic>Female</topic><topic>Gadolinium</topic><topic>Helper cells</topic><topic>Humans</topic><topic>IgG antibody</topic><topic>Immunoassay</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulins</topic><topic>Inflammatory diseases</topic><topic>Interferon</topic><topic>Interleukin 6</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Macrophages</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Nervous system</topic><topic>Nervous system diseases</topic><topic>Pleocytosis</topic><topic>Sarcoidosis</topic><topic>Sarcoidosis - blood</topic><topic>Sarcoidosis - cerebrospinal fluid</topic><topic>Sarcoidosis - diagnosis</topic><topic>Tumor necrosis factor</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mangioris, Georgios</creatorcontrib><creatorcontrib>Pittock, Sean J.</creatorcontrib><creatorcontrib>Yang, Binxia</creatorcontrib><creatorcontrib>Fryer, James P.</creatorcontrib><creatorcontrib>Harmsen, William S.</creatorcontrib><creatorcontrib>Dubey, Divyanshu</creatorcontrib><creatorcontrib>Flanagan, Eoin P.</creatorcontrib><creatorcontrib>Lopez‐Chiriboga, Sebastian A.</creatorcontrib><creatorcontrib>McKeon, Andrew</creatorcontrib><creatorcontrib>Mills, John R.</creatorcontrib><creatorcontrib>Vodopivec, Ivana</creatorcontrib><creatorcontrib>Tobin, W. Oliver</creatorcontrib><creatorcontrib>Toledano, Michel</creatorcontrib><creatorcontrib>Aksamit, Allen J.</creatorcontrib><creatorcontrib>Zekeridou, Anastasia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mangioris, Georgios</au><au>Pittock, Sean J.</au><au>Yang, Binxia</au><au>Fryer, James P.</au><au>Harmsen, William S.</au><au>Dubey, Divyanshu</au><au>Flanagan, Eoin P.</au><au>Lopez‐Chiriboga, Sebastian A.</au><au>McKeon, Andrew</au><au>Mills, John R.</au><au>Vodopivec, Ivana</au><au>Tobin, W. Oliver</au><au>Toledano, Michel</au><au>Aksamit, Allen J.</au><au>Zekeridou, Anastasia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2024-10</date><risdate>2024</risdate><volume>96</volume><issue>4</issue><spage>704</spage><epage>714</epage><pages>704-714</pages><issn>0364-5134</issn><issn>1531-8249</issn><eissn>1531-8249</eissn><abstract>Objective
To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.
Methods
In this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17A, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and tumor necrosis factor [TNF]‐alpha) in a multiplexed automated immunoassay system (ELLA; Bio‐Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011–02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin‐4 immunoglobulin G positivity, non‐inflammatory disorders, and healthy individuals were used as controls.
Results
A total of 32 NS patients (59% women; median age, 59 years [19–81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin‐4 immunoglobulin G positive, and 34 patients with non‐inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL‐2, IL‐6, IL‐10, IL‐13, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and TNF‐alpha levels were significantly higher in NS patients compared with non‐inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL‐6, CXCL9, CXCL10, GM‐CSF, interferon‐gamma, and TNF‐alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL‐6, IL‐10, IL‐13, CXCL9, CXL10, GM‐CSF, and TNF‐alpha associated with measures of disease activity.
Interpretation
NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B‐cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704–714</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>39031103</pmid><doi>10.1002/ana.27024</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5653-5600</orcidid><orcidid>https://orcid.org/0000-0002-6661-2910</orcidid><orcidid>https://orcid.org/0000-0002-1960-9065</orcidid><orcidid>https://orcid.org/0000-0001-5051-1739</orcidid><orcidid>https://orcid.org/0000-0001-6865-9045</orcidid><orcidid>https://orcid.org/0000-0001-6856-8143</orcidid><orcidid>https://orcid.org/0000-0002-9046-7880</orcidid><orcidid>https://orcid.org/0000-0002-6140-5584</orcidid><orcidid>https://orcid.org/0000-0002-8141-2394</orcidid></addata></record> |
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recordid | cdi_proquest_miscellaneous_3082959323 |
source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
subjects | Adult Aged Aquaporins Autoimmune diseases Biomarkers - blood Biomarkers - cerebrospinal fluid BLyS protein Case-Control Studies Central nervous system Central Nervous System Diseases - blood Central Nervous System Diseases - cerebrospinal fluid Central Nervous System Diseases - diagnosis Cerebrospinal fluid Chemokines Chemokines - blood Chemokines - cerebrospinal fluid CXCL10 protein CXCL13 protein Cytokines Cytokines - blood Cytokines - cerebrospinal fluid Diagnosis Diagnosis, Differential Differential diagnosis Disorders Female Gadolinium Helper cells Humans IgG antibody Immunoassay Immunoglobulin G Immunoglobulins Inflammatory diseases Interferon Interleukin 6 Lymphocytes Lymphocytes T Lymphoma Macrophages Male Middle Aged Multiple sclerosis Nervous system Nervous system diseases Pleocytosis Sarcoidosis Sarcoidosis - blood Sarcoidosis - cerebrospinal fluid Sarcoidosis - diagnosis Tumor necrosis factor Tumor necrosis factor-TNF |
title | Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T01%3A46%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cerebrospinal%20Fluid%20Cytokine%20and%20Chemokine%20Profiles%20in%20Central%20Nervous%20System%20Sarcoidosis:%20Diagnostic%20and%20Immunopathologic%20Insights&rft.jtitle=Annals%20of%20neurology&rft.au=Mangioris,%20Georgios&rft.date=2024-10&rft.volume=96&rft.issue=4&rft.spage=704&rft.epage=714&rft.pages=704-714&rft.issn=0364-5134&rft.eissn=1531-8249&rft_id=info:doi/10.1002/ana.27024&rft_dat=%3Cproquest_cross%3E3082959323%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3123660943&rft_id=info:pmid/39031103&rfr_iscdi=true |