{"id":{"repo_id":"birmingham","oai_identifier":"oai:etheses.bham.ac.uk:691"},"canonical_url":"https://search.dev.ndltd.org/etd/birmingham/oai:etheses.bham.ac.uk:691","repository":{"repo_id":"birmingham","name":"University of Birmingham","base_url":"https://etheses.bham.ac.uk/cgi/oai2"},"display":{"title":"Probing the sensitivity of autoantibody production to B cell depletion by Rituximab","abstract":"Rituximab, a monoclonal antibody directed against the human CD20 antigen, causes profound depletion of all B cells. When used in patients with autoimmune disease, IgG autoantibody titres often fall whilst serum IgG anti-tetanus toxoid antibody titres are unaffected. Antibodies of both these antibody specificities have features associated with production by long-lived CD20- plasma cells that should be resistant to Rituximab. Reasons for the differential loss of these apparently similar types of antibody were investigated. Initial experiments established multiplexed bead assays to measure, in parallel, serum titres of multiple antibody specificities. Paired acute and convalescent sera, from 11 patients treated with Rituximab for Wegener‟s granulomatosis, were then studied. During 5 months after treatment, and following clinical remission, IgG anti-Proteinase 3 autoantibody titres fell gradually. All other measured antibody titres remained little changed. These findings favour the hypothesis that autoantibody producing plasma cells are sustained by disease related inflammation. Subsequent experimental studies support a wider hypothesis -that inflamed sites can support increased plasma cell numbers. In the prolific humoral response of QM mice to immunisation with NP-Ficoll, concurrent infection with attenuated Salmonella enterica serovar Typhimurium increases splenic capacity to support plasma cells. The enhanced support may reflect locally increased IL-6 production.","abstract_html":"Rituximab, a monoclonal antibody directed against the human CD20 antigen, causes profound depletion of all B cells. When used in patients with autoimmune disease, IgG autoantibody titres often fall whilst serum IgG anti-tetanus toxoid antibody titres are unaffected. Antibodies of both these antibody specificities have features associated with production by long-lived CD20- plasma cells that should be resistant to Rituximab. Reasons for the differential loss of these apparently similar types of antibody were investigated. Initial experiments established multiplexed bead assays to measure, in parallel, serum titres of multiple antibody specificities. Paired acute and convalescent sera, from 11 patients treated with Rituximab for Wegener‟s granulomatosis, were then studied. During 5 months after treatment, and following clinical remission, IgG anti-Proteinase 3 autoantibody titres fell gradually. All other measured antibody titres remained little changed. These findings favour the hypothesis that autoantibody producing plasma cells are sustained by disease related inflammation. Subsequent experimental studies support a wider hypothesis -that inflamed sites can support increased plasma cell numbers. In the prolific humoral response of QM mice to immunisation with NP-Ficoll, concurrent infection with attenuated Salmonella enterica serovar Typhimurium increases splenic capacity to support plasma cells. The enhanced support may reflect locally increased IL-6 production.","abstract_has_math":false,"creators":["Ferraro, Alastair James"],"institution":"University of Birmingham","degree_name":"d_ph","degree_level":"d_ph","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07","date_published":"2010-07","updated_at":"2026-07-24T01:11:06Z","subjects":["RA Public aspects of medicine"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["mrc"]},{"key":"dc:creator","label":"Author","values":["Ferraro, Alastair James"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07"]},{"key":"dc:date.issued","label":"Date","values":["2010-07"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["College of Medical & Dental Sciences","School of Immunity and Infection"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Birmingham"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["http://etheses.bham.ac.uk//id/eprint/691/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["d_ph"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["d_ph"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["RA Public aspects of medicine"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://etheses.bham.ac.uk//id/eprint/691/1/Ferraro10PhD.pdf","http://etheses.bham.ac.uk//id/eprint/691/2/Decl_IS_FerraroPhD.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Rituximab, a monoclonal antibody directed against the human CD20 antigen, causes profound depletion of all B cells. When used in patients with autoimmune disease, IgG autoantibody titres often fall whilst serum IgG anti-tetanus toxoid antibody titres are unaffected. Antibodies of both these antibody specificities have features associated with production by long-lived CD20- plasma cells that should be resistant to Rituximab. Reasons for the differential loss of these apparently similar types of antibody were investigated. Initial experiments established multiplexed bead assays to measure, in parallel, serum titres of multiple antibody specificities. Paired acute and convalescent sera, from 11 patients treated with Rituximab for Wegener‟s granulomatosis, were then studied. During 5 months after treatment, and following clinical remission, IgG anti-Proteinase 3 autoantibody titres fell gradually. All other measured antibody titres remained little changed. These findings favour the hypothesis that autoantibody producing plasma cells are sustained by disease related inflammation. Subsequent experimental studies support a wider hypothesis -that inflamed sites can support increased plasma cell numbers. In the prolific humoral response of QM mice to immunisation with NP-Ficoll, concurrent infection with attenuated Salmonella enterica serovar Typhimurium increases splenic capacity to support plasma cells. The enhanced support may reflect locally increased IL-6 production."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Probing the sensitivity of autoantibody production to B cell depletion by Rituximab"]}]}],"canonical_facts":{"dc:contributor.sponsor":["mrc"],"dc:creator":["Ferraro, Alastair James"],"dc:date":["2010-07"],"dc:date.issued":["2010-07"],"dc:description.abstract":["Rituximab, a monoclonal antibody directed against the human CD20 antigen, causes profound depletion of all B cells. When used in patients with autoimmune disease, IgG autoantibody titres often fall whilst serum IgG anti-tetanus toxoid antibody titres are unaffected. Antibodies of both these antibody specificities have features associated with production by long-lived CD20- plasma cells that should be resistant to Rituximab. Reasons for the differential loss of these apparently similar types of antibody were investigated. Initial experiments established multiplexed bead assays to measure, in parallel, serum titres of multiple antibody specificities. Paired acute and convalescent sera, from 11 patients treated with Rituximab for Wegener‟s granulomatosis, were then studied. During 5 months after treatment, and following clinical remission, IgG anti-Proteinase 3 autoantibody titres fell gradually. All other measured antibody titres remained little changed. These findings favour the hypothesis that autoantibody producing plasma cells are sustained by disease related inflammation. Subsequent experimental studies support a wider hypothesis -that inflamed sites can support increased plasma cell numbers. In the prolific humoral response of QM mice to immunisation with NP-Ficoll, concurrent infection with attenuated Salmonella enterica serovar Typhimurium increases splenic capacity to support plasma cells. 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