Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis
IMPORTANCE: Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and m...
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| Veröffentlicht in: | JAMA neurology 2018-04, Vol.75 (4), p.428-435 |
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| description | IMPORTANCE: Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response. OBJECTIVE: To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis. DESIGN, SETTING AND PARTICIPANTS: This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded. MAIN OUTCOMES AND MEASURES: The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters. RESULTS: The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P |
| doi_str_mv | 10.1001/jamaneurol.2017.4842 |
| format | Article |
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Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response. OBJECTIVE: To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis. DESIGN, SETTING AND PARTICIPANTS: This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded. MAIN OUTCOMES AND MEASURES: The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters. RESULTS: The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P < .001). Radiological improvements were found in 4 (25%), 22 (56%), and 1 (11%) of patients with patterns 1, 2, and 3, respectively. The respective rates of response measured by changes in Expanded Disability Status Scale scores were 25%, 40%, and 0%. Brainstem involvement was a negative predictive factor for the functional therapy response (logarithmic odds ratio [logOR], −1.43; 95% CI, −3.21 to 0.17; P = .03), while immunoadsorption (as compared with plasma exchange) might be a positive predictive factor (logOR, 3.26; 95% CI, 0.75 to 8.13; P = .01). CONCLUSIONS AND RELEVANCE: This cohort study provides evidence that the response to apheresis treatment is associated with immunopathological patterns. Patients with both patterns 1 and 2 improved clinically after apheresis treatment, but pattern 2 patients who showed signs of a humoral immune response benefited most. Apheresis appears unlikely to benefit patients with pattern 3 lesions.</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2017.4842</identifier><identifier>PMID: 29404583</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adult ; Blood Component Removal - methods ; Cohort Studies ; Disability Evaluation ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis - immunology ; Multiple Sclerosis - pathology ; Multiple Sclerosis - therapy ; Online First ; Original Investigation ; Treatment Outcome</subject><ispartof>JAMA neurology, 2018-04, Vol.75 (4), p.428-435</ispartof><rights>Copyright 2018 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a427t-2d7e0b079fb78f6cd1b8c0a9435c90e1078df2e79111741148fd16ce856874ff3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2017.4842$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2017.4842$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,777,781,882,3327,27905,27906,76238,76241</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29404583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stork, Lidia</creatorcontrib><creatorcontrib>Ellenberger, David</creatorcontrib><creatorcontrib>Beißbarth, Tim</creatorcontrib><creatorcontrib>Friede, Tim</creatorcontrib><creatorcontrib>Lucchinetti, Claudia F</creatorcontrib><creatorcontrib>Brück, Wolfgang</creatorcontrib><creatorcontrib>Metz, Imke</creatorcontrib><title>Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis</title><title>JAMA neurology</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response. OBJECTIVE: To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis. DESIGN, SETTING AND PARTICIPANTS: This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded. MAIN OUTCOMES AND MEASURES: The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters. RESULTS: The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P < .001). Radiological improvements were found in 4 (25%), 22 (56%), and 1 (11%) of patients with patterns 1, 2, and 3, respectively. The respective rates of response measured by changes in Expanded Disability Status Scale scores were 25%, 40%, and 0%. Brainstem involvement was a negative predictive factor for the functional therapy response (logarithmic odds ratio [logOR], −1.43; 95% CI, −3.21 to 0.17; P = .03), while immunoadsorption (as compared with plasma exchange) might be a positive predictive factor (logOR, 3.26; 95% CI, 0.75 to 8.13; P = .01). CONCLUSIONS AND RELEVANCE: This cohort study provides evidence that the response to apheresis treatment is associated with immunopathological patterns. Patients with both patterns 1 and 2 improved clinically after apheresis treatment, but pattern 2 patients who showed signs of a humoral immune response benefited most. Apheresis appears unlikely to benefit patients with pattern 3 lesions.</description><subject>Adult</subject><subject>Blood Component Removal - methods</subject><subject>Cohort Studies</subject><subject>Disability Evaluation</subject><subject>Female</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - pathology</subject><subject>Multiple Sclerosis - therapy</subject><subject>Online First</subject><subject>Original Investigation</subject><subject>Treatment Outcome</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdFuFCEUhonR2Kb2BYwxXHqzKzDMwNyYNKu1TWpsao2XhGUOHRpmGIFpsu_hA8tk69ZywyH_f_7DyYfQO0rWlBD68V4PeoQ5Br9mhIo1l5y9QMeMNnLV0Fq8PNS8PUKnKd2TciQhvOKv0RFrOeG1rI7Rn8_OWogwGkjYjTj3gG9gCmMq7xzw2dQXNbmEb0uhpx0OFl_r7GDMCf9yuccVvnAph0nnPvhw54z2foc3XqfkrIMOXw7DPD7Tl4QMcUxL2rfZZzd5wD-MhxjKrDfoldU-wenjfYJ-nn-53Vysrr5_vdycXa00ZyKvWCeAbIlo7VZI25iObqUhuuVVbVoClAjZWQaipZQKTimXtqONAVk3UnBrqxP0aZ87zdsBOlN2itqrKbpBx50K2qnnyuh6dRceVC1lzUhbAj48BsTwe4aU1eCSAe8LnDAnRdu2przhjBQr31tNWTFFsIcxlKiFqXpiqhamamFa2t7__8VD0z-CxfB2byjdT2ojCumm-guj66z7</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Stork, Lidia</creator><creator>Ellenberger, David</creator><creator>Beißbarth, Tim</creator><creator>Friede, Tim</creator><creator>Lucchinetti, Claudia F</creator><creator>Brück, Wolfgang</creator><creator>Metz, Imke</creator><general>American Medical Association</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180401</creationdate><title>Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis</title><author>Stork, Lidia ; Ellenberger, David ; Beißbarth, Tim ; Friede, Tim ; Lucchinetti, Claudia F ; Brück, Wolfgang ; Metz, Imke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a427t-2d7e0b079fb78f6cd1b8c0a9435c90e1078df2e79111741148fd16ce856874ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Blood Component Removal - methods</topic><topic>Cohort Studies</topic><topic>Disability Evaluation</topic><topic>Female</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - pathology</topic><topic>Multiple Sclerosis - therapy</topic><topic>Online First</topic><topic>Original Investigation</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stork, Lidia</creatorcontrib><creatorcontrib>Ellenberger, David</creatorcontrib><creatorcontrib>Beißbarth, Tim</creatorcontrib><creatorcontrib>Friede, Tim</creatorcontrib><creatorcontrib>Lucchinetti, Claudia F</creatorcontrib><creatorcontrib>Brück, Wolfgang</creatorcontrib><creatorcontrib>Metz, Imke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stork, Lidia</au><au>Ellenberger, David</au><au>Beißbarth, Tim</au><au>Friede, Tim</au><au>Lucchinetti, Claudia F</au><au>Brück, Wolfgang</au><au>Metz, Imke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis</atitle><jtitle>JAMA neurology</jtitle><addtitle>JAMA Neurol</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>75</volume><issue>4</issue><spage>428</spage><epage>435</epage><pages>428-435</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response. OBJECTIVE: To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis. DESIGN, SETTING AND PARTICIPANTS: This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded. MAIN OUTCOMES AND MEASURES: The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters. RESULTS: The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P < .001). Radiological improvements were found in 4 (25%), 22 (56%), and 1 (11%) of patients with patterns 1, 2, and 3, respectively. The respective rates of response measured by changes in Expanded Disability Status Scale scores were 25%, 40%, and 0%. Brainstem involvement was a negative predictive factor for the functional therapy response (logarithmic odds ratio [logOR], −1.43; 95% CI, −3.21 to 0.17; P = .03), while immunoadsorption (as compared with plasma exchange) might be a positive predictive factor (logOR, 3.26; 95% CI, 0.75 to 8.13; P = .01). CONCLUSIONS AND RELEVANCE: This cohort study provides evidence that the response to apheresis treatment is associated with immunopathological patterns. Patients with both patterns 1 and 2 improved clinically after apheresis treatment, but pattern 2 patients who showed signs of a humoral immune response benefited most. Apheresis appears unlikely to benefit patients with pattern 3 lesions.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>29404583</pmid><doi>10.1001/jamaneurol.2017.4842</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Medical Association Journal |
| subjects | Adult Blood Component Removal - methods Cohort Studies Disability Evaluation Female Humans Magnetic Resonance Imaging Male Middle Aged Multiple Sclerosis - immunology Multiple Sclerosis - pathology Multiple Sclerosis - therapy Online First Original Investigation Treatment Outcome |
| title | Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis |
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