Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies
Summary Background Therapies targeting the T cell‐mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T‐cell counts in both compartments have be...
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| Veröffentlicht in: | British journal of dermatology (1951) 2008-07, Vol.159 (1), p.91-96 |
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| creator | Van Lingen, R.G. Körver, J.E.M. Van De Kerkhof, P.C.M. Berends, M.A.M. Van Rens, D.W.A. Langewouters, A.M. Boezeman, J.B.M. Seyger, M.M.B. De Jong, E.M.G.J. |
| description | Summary
Background Therapies targeting the T cell‐mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T‐cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them.
Objectives To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune‐targeted antipsoriatic therapies.
Methods Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T‐cell subsets and simultaneously T‐cell subsets were isolated from PB specimens by flow cytometry.
Results The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T‐cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T‐cell subsets were significantly decreased. With respect to etanercept, few significant changes in T‐cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status.
Conclusions Treatment with efalizumab establishes successful recompartmentalization of T‐cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept‐treated patients, a significant clinical response is no guarantee for significant changes in T‐cell subsets in the different compartments. Reductions in T‐cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T‐cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept. |
| doi_str_mv | 10.1111/j.1365-2133.2008.08618.x |
| format | Article |
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Background Therapies targeting the T cell‐mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T‐cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them.
Objectives To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune‐targeted antipsoriatic therapies.
Methods Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T‐cell subsets and simultaneously T‐cell subsets were isolated from PB specimens by flow cytometry.
Results The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T‐cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T‐cell subsets were significantly decreased. With respect to etanercept, few significant changes in T‐cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status.
Conclusions Treatment with efalizumab establishes successful recompartmentalization of T‐cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept‐treated patients, a significant clinical response is no guarantee for significant changes in T‐cell subsets in the different compartments. Reductions in T‐cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T‐cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/j.1365-2133.2008.08618.x</identifier><identifier>PMID: 18476954</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Antibodies, Monoclonal - therapeutic use ; compartmentalization ; Dermatologic Agents - therapeutic use ; Epidermis - drug effects ; Etanercept ; Female ; Flow Cytometry ; Humans ; Immunoglobulin G - therapeutic use ; Immunosuppressive Agents - therapeutic use ; Male ; Middle Aged ; peripheral blood ; psoriasis ; Psoriasis - drug therapy ; Psoriasis - immunology ; Receptors, Tumor Necrosis Factor - therapeutic use ; Severity of Illness Index ; skin ; T cells ; T-Lymphocyte Subsets - drug effects ; T-Lymphocyte Subsets - immunology ; Treatment Outcome</subject><ispartof>British journal of dermatology (1951), 2008-07, Vol.159 (1), p.91-96</ispartof><rights>2008 The Authors. Journal Compilation © 2008 British Association of Dermatologists</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4368-23adc611c8018686d51b886b701eb9ade41097bbef64beb6bb6ed89efe93570e3</citedby><cites>FETCH-LOGICAL-c4368-23adc611c8018686d51b886b701eb9ade41097bbef64beb6bb6ed89efe93570e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2133.2008.08618.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2133.2008.08618.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18476954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Lingen, R.G.</creatorcontrib><creatorcontrib>Körver, J.E.M.</creatorcontrib><creatorcontrib>Van De Kerkhof, P.C.M.</creatorcontrib><creatorcontrib>Berends, M.A.M.</creatorcontrib><creatorcontrib>Van Rens, D.W.A.</creatorcontrib><creatorcontrib>Langewouters, A.M.</creatorcontrib><creatorcontrib>Boezeman, J.B.M.</creatorcontrib><creatorcontrib>Seyger, M.M.B.</creatorcontrib><creatorcontrib>De Jong, E.M.G.J.</creatorcontrib><title>Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies</title><title>British journal of dermatology (1951)</title><addtitle>Br J Dermatol</addtitle><description>Summary
Background Therapies targeting the T cell‐mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T‐cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them.
Objectives To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune‐targeted antipsoriatic therapies.
Methods Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T‐cell subsets and simultaneously T‐cell subsets were isolated from PB specimens by flow cytometry.
Results The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T‐cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T‐cell subsets were significantly decreased. With respect to etanercept, few significant changes in T‐cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status.
Conclusions Treatment with efalizumab establishes successful recompartmentalization of T‐cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept‐treated patients, a significant clinical response is no guarantee for significant changes in T‐cell subsets in the different compartments. Reductions in T‐cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T‐cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.</description><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>compartmentalization</subject><subject>Dermatologic Agents - therapeutic use</subject><subject>Epidermis - drug effects</subject><subject>Etanercept</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>peripheral blood</subject><subject>psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - immunology</subject><subject>Receptors, Tumor Necrosis Factor - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>skin</subject><subject>T cells</subject><subject>T-Lymphocyte Subsets - drug effects</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Treatment Outcome</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctu1TAQhi0EoofCKyCv2CXYceILEgsobYG2IFAREhvLdibgQ27YTjnlGXhoEnJUlmU2HtnfN7b1I4QpyelcT7c5ZbzKCspYXhAicyI5lfnuDtrcHNxFG0KIyIji7AA9iHFLCGWkIvfRAZWl4KoqN-j3R2jhyvQO8NBgN3SjCamDPpnW_zLJD_2yf5k5aFscJxshRdwMAbvW996ZFvtuDMMVLA72PR7jELyJPj7D0DTg0uL7rpt6yJIJXyFBjU2f_Aom73D6BsGMHuJDdK8xbYRH-_UQfTo5vjx6nZ2_P31z9OI8cyXjMiuYqR2n1ElCJZe8rqiVkltBKFhlaigpUcJaaHhpwXJrOdRSQQOKVYIAO0RP1rnzy39MEJPufFx-aHoYpqi5KoRSorgVLIiigvNqBuUKujDEGKDRY_CdCdeaEr1Eprd6SUYvyeglMv03Mr2b1cf7OybbQf1P3Gc0A89X4Kdv4fq_B-uXb18t3exnq-9jgt2Nb8J3zQUTlf787lRX5dmHorr4os_YH1Vft-U</recordid><startdate>200807</startdate><enddate>200807</enddate><creator>Van Lingen, R.G.</creator><creator>Körver, J.E.M.</creator><creator>Van De Kerkhof, P.C.M.</creator><creator>Berends, M.A.M.</creator><creator>Van Rens, D.W.A.</creator><creator>Langewouters, A.M.</creator><creator>Boezeman, J.B.M.</creator><creator>Seyger, M.M.B.</creator><creator>De Jong, E.M.G.J.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200807</creationdate><title>Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies</title><author>Van Lingen, R.G. ; Körver, J.E.M. ; Van De Kerkhof, P.C.M. ; Berends, M.A.M. ; Van Rens, D.W.A. ; Langewouters, A.M. ; Boezeman, J.B.M. ; Seyger, M.M.B. ; De Jong, E.M.G.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4368-23adc611c8018686d51b886b701eb9ade41097bbef64beb6bb6ed89efe93570e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>compartmentalization</topic><topic>Dermatologic Agents - therapeutic use</topic><topic>Epidermis - drug effects</topic><topic>Etanercept</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Male</topic><topic>Middle Aged</topic><topic>peripheral blood</topic><topic>psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - immunology</topic><topic>Receptors, Tumor Necrosis Factor - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>skin</topic><topic>T cells</topic><topic>T-Lymphocyte Subsets - drug effects</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Lingen, R.G.</creatorcontrib><creatorcontrib>Körver, J.E.M.</creatorcontrib><creatorcontrib>Van De Kerkhof, P.C.M.</creatorcontrib><creatorcontrib>Berends, M.A.M.</creatorcontrib><creatorcontrib>Van Rens, D.W.A.</creatorcontrib><creatorcontrib>Langewouters, A.M.</creatorcontrib><creatorcontrib>Boezeman, J.B.M.</creatorcontrib><creatorcontrib>Seyger, M.M.B.</creatorcontrib><creatorcontrib>De Jong, E.M.G.J.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Lingen, R.G.</au><au>Körver, J.E.M.</au><au>Van De Kerkhof, P.C.M.</au><au>Berends, M.A.M.</au><au>Van Rens, D.W.A.</au><au>Langewouters, A.M.</au><au>Boezeman, J.B.M.</au><au>Seyger, M.M.B.</au><au>De Jong, E.M.G.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2008-07</date><risdate>2008</risdate><volume>159</volume><issue>1</issue><spage>91</spage><epage>96</epage><pages>91-96</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><abstract>Summary
Background Therapies targeting the T cell‐mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T‐cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them.
Objectives To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune‐targeted antipsoriatic therapies.
Methods Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T‐cell subsets and simultaneously T‐cell subsets were isolated from PB specimens by flow cytometry.
Results The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T‐cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T‐cell subsets were significantly decreased. With respect to etanercept, few significant changes in T‐cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status.
Conclusions Treatment with efalizumab establishes successful recompartmentalization of T‐cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept‐treated patients, a significant clinical response is no guarantee for significant changes in T‐cell subsets in the different compartments. Reductions in T‐cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T‐cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18476954</pmid><doi>10.1111/j.1365-2133.2008.08618.x</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Antibodies, Monoclonal - therapeutic use compartmentalization Dermatologic Agents - therapeutic use Epidermis - drug effects Etanercept Female Flow Cytometry Humans Immunoglobulin G - therapeutic use Immunosuppressive Agents - therapeutic use Male Middle Aged peripheral blood psoriasis Psoriasis - drug therapy Psoriasis - immunology Receptors, Tumor Necrosis Factor - therapeutic use Severity of Illness Index skin T cells T-Lymphocyte Subsets - drug effects T-Lymphocyte Subsets - immunology Treatment Outcome |
| title | Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies |
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