Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies
Abstract Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2009-03, Vol.130 (3), p.252-258 |
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| creator | El Fassi, Daniel Banga, J. Paul Gilbert, Jacqueline A Padoa, Carolyn Hegedüs, Laszlo Nielsen, Claus H |
| description | Abstract Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66 ± 22%, upon treatment with rituximab and methimazole for 21 days ( p < 0.0001), compared to an increase by 33% on average (NS) in patients receiving methimazole alone ( p = 0.04 between groups). The overall levels of TRAbs decreased by around 15% in both groups. Within one year of follow-up, rituximab therapy mediated specific decreases in thyroid-peroxidase antibody- and IgM levels, whereas IgG levels were unaffected. The data indicate that rituximab therapy has differential effects on pathogenic and non-pathogenic autoantibodies, even when directed against the same antigen. The possible mechanisms underlying this hitherto unappreciated phenomenon are discussed. |
| doi_str_mv | 10.1016/j.clim.2008.09.007 |
| format | Article |
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Paul ; Gilbert, Jacqueline A ; Padoa, Carolyn ; Hegedüs, Laszlo ; Nielsen, Claus H</creator><creatorcontrib>El Fassi, Daniel ; Banga, J. Paul ; Gilbert, Jacqueline A ; Padoa, Carolyn ; Hegedüs, Laszlo ; Nielsen, Claus H</creatorcontrib><description>Abstract Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66 ± 22%, upon treatment with rituximab and methimazole for 21 days ( p < 0.0001), compared to an increase by 33% on average (NS) in patients receiving methimazole alone ( p = 0.04 between groups). The overall levels of TRAbs decreased by around 15% in both groups. Within one year of follow-up, rituximab therapy mediated specific decreases in thyroid-peroxidase antibody- and IgM levels, whereas IgG levels were unaffected. The data indicate that rituximab therapy has differential effects on pathogenic and non-pathogenic autoantibodies, even when directed against the same antigen. The possible mechanisms underlying this hitherto unappreciated phenomenon are discussed.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2008.09.007</identifier><identifier>PMID: 18964302</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Allergy and Immunology ; Animals ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; Antibody Formation - drug effects ; Autoantibodies - blood ; Autoantibody ; Autoimmunity ; B lymphocyte ; Bioactivity ; Biological and medical sciences ; CD20 ; CHO Cells ; Cricetinae ; Cricetulus ; Cyclic AMP - metabolism ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Graves Disease - drug therapy ; Graves Disease - immunology ; Graves' disease ; Humans ; Immunoglobulin ; Immunoglobulins, Thyroid-Stimulating - drug effects ; Immunoglobulins, Thyroid-Stimulating - metabolism ; Immunologic Factors - therapeutic use ; Immunotherapy ; Medical sciences ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Rituximab ; Thyroid. 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Paul</creatorcontrib><creatorcontrib>Gilbert, Jacqueline A</creatorcontrib><creatorcontrib>Padoa, Carolyn</creatorcontrib><creatorcontrib>Hegedüs, Laszlo</creatorcontrib><creatorcontrib>Nielsen, Claus H</creatorcontrib><title>Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Abstract Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66 ± 22%, upon treatment with rituximab and methimazole for 21 days ( p < 0.0001), compared to an increase by 33% on average (NS) in patients receiving methimazole alone ( p = 0.04 between groups). The overall levels of TRAbs decreased by around 15% in both groups. Within one year of follow-up, rituximab therapy mediated specific decreases in thyroid-peroxidase antibody- and IgM levels, whereas IgG levels were unaffected. The data indicate that rituximab therapy has differential effects on pathogenic and non-pathogenic autoantibodies, even when directed against the same antigen. The possible mechanisms underlying this hitherto unappreciated phenomenon are discussed.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Murine-Derived</subject><subject>Antibody Formation - drug effects</subject><subject>Autoantibodies - blood</subject><subject>Autoantibody</subject><subject>Autoimmunity</subject><subject>B lymphocyte</subject><subject>Bioactivity</subject><subject>Biological and medical sciences</subject><subject>CD20</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Cyclic AMP - metabolism</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Graves Disease - drug therapy</subject><subject>Graves Disease - immunology</subject><subject>Graves' disease</subject><subject>Humans</subject><subject>Immunoglobulin</subject><subject>Immunoglobulins, Thyroid-Stimulating - drug effects</subject><subject>Immunoglobulins, Thyroid-Stimulating - metabolism</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Immunotherapy</subject><subject>Medical sciences</subject><subject>Non tumoral diseases. Target tissue resistance. Benign neoplasms</subject><subject>Rituximab</subject><subject>Thyroid. Thyroid axis (diseases)</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2LFDEQhhtR3A_9Ax4kF_U0YyXdSScggizuKix4cD2HdFLtZOzujEl6df69aaZR8KCnJPBUUXmfqqpnFLYUqHi939rBj1sGILegtgDtg-qcckY3LdT84XoXgoqz6iKlPQBwxsTj6oxKJZoa2Hk130U0ecQpk9CTm2juMb0izic0CckPn3ck-jz_9KPpSDqg9b23ZhiOJKKbLSaSd0gOMZRH9mFauuTdMQbvSMp-nAeT_fSVmDkHM2XfBecxPake9WZI-HQ9L6sv1-_vrj5sbj_dfLx6d7uxTQt5I3pBQdqWN51TUNfcdS3va5S8MbQFZIpD21LmuJIgoaFWUdc4ymRnsZF9fVm9PPUtA36fMWU9-mRxGMyEYU5aCKkk5-1_QVYCFaxWBWQn0MaQUsReH2LJJh41Bb1Y0Xu9WNGLFQ1KFyul6Pnafe5GdH9KVg0FeLECJpV0-2gm69NvjlGqoPyxcG9OHJbQ7j1GnazHyaLzEW3WLvh_z_H2r_KCTIvPb3jEtA9znIoOTXViGvTnZX-W9SnZgmSK1b8A7k7BCQ</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>El Fassi, Daniel</creator><creator>Banga, J. 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Paul ; Gilbert, Jacqueline A ; Padoa, Carolyn ; Hegedüs, Laszlo ; Nielsen, Claus H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-6f6108c754bd90335db75f3e854a170e29507712d59808041c91d4d128bce48f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Murine-Derived</topic><topic>Antibody Formation - drug effects</topic><topic>Autoantibodies - blood</topic><topic>Autoantibody</topic><topic>Autoimmunity</topic><topic>B lymphocyte</topic><topic>Bioactivity</topic><topic>Biological and medical sciences</topic><topic>CD20</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Cyclic AMP - metabolism</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. 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Paul</creatorcontrib><creatorcontrib>Gilbert, Jacqueline A</creatorcontrib><creatorcontrib>Padoa, Carolyn</creatorcontrib><creatorcontrib>Hegedüs, Laszlo</creatorcontrib><creatorcontrib>Nielsen, Claus H</creatorcontrib><collection>Pascal-Francis</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>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Fassi, Daniel</au><au>Banga, J. 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| subjects | Allergy and Immunology Animals Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Murine-Derived Antibody Formation - drug effects Autoantibodies - blood Autoantibody Autoimmunity B lymphocyte Bioactivity Biological and medical sciences CD20 CHO Cells Cricetinae Cricetulus Cyclic AMP - metabolism Endocrinopathies Fundamental and applied biological sciences. Psychology Fundamental immunology Graves Disease - drug therapy Graves Disease - immunology Graves' disease Humans Immunoglobulin Immunoglobulins, Thyroid-Stimulating - drug effects Immunoglobulins, Thyroid-Stimulating - metabolism Immunologic Factors - therapeutic use Immunotherapy Medical sciences Non tumoral diseases. Target tissue resistance. Benign neoplasms Rituximab Thyroid. Thyroid axis (diseases) |
| title | Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies |
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