Rituximab Exerts a Dual Effect in Pemphigus Vulgaris
Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting the skin and mucous membranes. Autoreactive CD4+ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV w...
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| Veröffentlicht in: | Journal of investigative dermatology 2008-12, Vol.128 (12), p.2850-2858 |
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| creator | Eming, Rüdiger Nagel, Angela Wolff-Franke, Sonja Podstawa, Eva Debus, Dirk Hertl, Michael |
| description | Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting the skin and mucous membranes. Autoreactive CD4+ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375mg per m2 body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4+ Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6–12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4+ Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3+CD4+ T lymphocytes and the frequency of tetanus toxoid-reactive CD4+ Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4+ Th cells. |
| doi_str_mv | 10.1038/jid.2008.172 |
| format | Article |
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Autoreactive CD4+ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375mg per m2 body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4+ Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6–12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4+ Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3+CD4+ T lymphocytes and the frequency of tetanus toxoid-reactive CD4+ Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4+ Th cells.</description><identifier>ISSN: 0022-202X</identifier><identifier>EISSN: 1523-1747</identifier><identifier>DOI: 10.1038/jid.2008.172</identifier><identifier>PMID: 18563178</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal, Murine-Derived ; Autoantibodies ; B-Lymphocytes - immunology ; CD3 Complex - biosynthesis ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; Dermatology ; Desmoglein 3 - metabolism ; Enzyme-linked immunosorbent assay ; Female ; Helper cells ; Humans ; Immunologic Factors - pharmacology ; Internet ; Lymphocytes B ; Lymphocytes T ; Male ; Middle Aged ; Pemphigus - drug therapy ; Pemphigus - immunology ; pemphigus vulgaris ; Peripheral blood ; Rituximab ; Skin diseases ; Surface area ; Tetanus ; Tetanus Toxoid - chemistry ; Th1 Cells - metabolism ; Th2 Cells - metabolism</subject><ispartof>Journal of investigative dermatology, 2008-12, Vol.128 (12), p.2850-2858</ispartof><rights>2008 The Society for Investigative Dermatology, Inc</rights><rights>Copyright Nature Publishing Group Dec 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-31341c8ec0ac131fc89577a2c6941e0d1a61713051b5ce718eca26ef9b9120c33</citedby><cites>FETCH-LOGICAL-c500t-31341c8ec0ac131fc89577a2c6941e0d1a61713051b5ce718eca26ef9b9120c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18563178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eming, Rüdiger</creatorcontrib><creatorcontrib>Nagel, Angela</creatorcontrib><creatorcontrib>Wolff-Franke, Sonja</creatorcontrib><creatorcontrib>Podstawa, Eva</creatorcontrib><creatorcontrib>Debus, Dirk</creatorcontrib><creatorcontrib>Hertl, Michael</creatorcontrib><title>Rituximab Exerts a Dual Effect in Pemphigus Vulgaris</title><title>Journal of investigative dermatology</title><addtitle>J Invest Dermatol</addtitle><description>Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting the skin and mucous membranes. Autoreactive CD4+ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375mg per m2 body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4+ Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6–12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4+ Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3+CD4+ T lymphocytes and the frequency of tetanus toxoid-reactive CD4+ Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4+ Th cells.</description><subject>Aged</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Murine-Derived</subject><subject>Autoantibodies</subject><subject>B-Lymphocytes - immunology</subject><subject>CD3 Complex - biosynthesis</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Dermatology</subject><subject>Desmoglein 3 - metabolism</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Helper cells</subject><subject>Humans</subject><subject>Immunologic Factors - pharmacology</subject><subject>Internet</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pemphigus - drug therapy</subject><subject>Pemphigus - immunology</subject><subject>pemphigus vulgaris</subject><subject>Peripheral blood</subject><subject>Rituximab</subject><subject>Skin diseases</subject><subject>Surface area</subject><subject>Tetanus</subject><subject>Tetanus Toxoid - chemistry</subject><subject>Th1 Cells - metabolism</subject><subject>Th2 Cells - metabolism</subject><issn>0022-202X</issn><issn>1523-1747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp90MFLHDEUx_EgLe5qvXkuQw_Fg7O-l8wkmWOxqxYWFKniLWQzb2yWmZ1tMlP0vzeyC4IUT-_y4Qfvy9gxwgxB6LOVr2ccQM9Q8T02xZKLHFWhPrEpAOc5B_4wYQcxrgBQFqXeZxPUpRSo9JQVt34Yn3xnl9n8icIQM5v9HG2bzZuG3JD5dXZD3eaPfxxjdj-2jzb4-IV9bmwb6Wh3D9ndxfz3-VW-uL78df5jkbsSYMgFigKdJgfWocDG6apUynInqwIJarQSFQoocVk6Upik5ZKaalkhByfEIfu-3d2E_u9IcTCdj47a1q6pH6ORlVIAEhI8-RAicA1KY1Um-u0dXfVjWKc3DE89pda6SOh0i1zoYwzUmE1IjcJzWjKv1U2qbl6rm1Q98a-7zXHZUf2Gd5kTkFtAqdY_T8FE52ntqPYhVTZ17_-__AJHmIyK</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Eming, Rüdiger</creator><creator>Nagel, Angela</creator><creator>Wolff-Franke, Sonja</creator><creator>Podstawa, Eva</creator><creator>Debus, Dirk</creator><creator>Hertl, Michael</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Rituximab Exerts a Dual Effect in Pemphigus Vulgaris</title><author>Eming, Rüdiger ; 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Autoreactive CD4+ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375mg per m2 body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4+ Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6–12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4+ Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3+CD4+ T lymphocytes and the frequency of tetanus toxoid-reactive CD4+ Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4+ Th cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18563178</pmid><doi>10.1038/jid.2008.172</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Murine-Derived Autoantibodies B-Lymphocytes - immunology CD3 Complex - biosynthesis CD4 antigen CD4-Positive T-Lymphocytes - immunology Dermatology Desmoglein 3 - metabolism Enzyme-linked immunosorbent assay Female Helper cells Humans Immunologic Factors - pharmacology Internet Lymphocytes B Lymphocytes T Male Middle Aged Pemphigus - drug therapy Pemphigus - immunology pemphigus vulgaris Peripheral blood Rituximab Skin diseases Surface area Tetanus Tetanus Toxoid - chemistry Th1 Cells - metabolism Th2 Cells - metabolism |
| title | Rituximab Exerts a Dual Effect in Pemphigus Vulgaris |
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