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dc.contributor.advisorYocum, David E.en_US
dc.contributor.authorHammaker, Deepa Rajan
dc.creatorHammaker, Deepa Rajanen_US
dc.date.accessioned2013-05-09T09:29:37Z
dc.date.available2013-05-09T09:29:37Z
dc.date.issued1999en_US
dc.identifier.urihttp://hdl.handle.net/10150/289074
dc.description.abstractObjectives. To (a) determine the immunological effects of a PRIMATIZED® anti-CD4 antibody alone or in combination with methotrexate in RA patients, (b) determine the immunological effects of a chimeric anti-CD25 antibody in RA patients who are partially refractive to methotrexate and (c) compare interleukin-15 levels in the serum of RA patients and healthy controls and determine if there is a correlation between this cytokine and serum TNF-α, CD 122 expression, and disease activity. Patients and methods. (a) Eight RA patients were selected, four received anti-CD4+ placebo and the other four received anti-CD4+ methotrexate for 4 weeks. The immunological effects were assessed on peripheral blood by flow cytometry and thymidine incorporation assays. (b) Six RA patients were given anti-CD25 antibody (0.02-60mg) along with methotrexate for 26 days. The immunological effects were assessed on peripheral blood by flow cytometry, thymidine assays, and ELISA. (c) Blood and disease activity from twenty-one RA patients were obtained and serum IL-15 and TNF-α levels were measured by ELISA. IL-15R β chain (CD 122) expression was measured by flow cytometry. Results. (a) The anti-CD4 antibody caused a selective and significant decrease in the number of CD4+ T cells. No inhibition of PHA or mitogenic antibody stimulated proliferation was observed. (b) The anti-CD25 antibody caused a significant decrease in the percent CD25+ cells. The antibody bound CD25 and prevented interaction of IL-2 and IL-2R. Anti-CD25 antibody caused a significant decrease in PHA or mitogenic antibody stimulated proliferation. Clinically, the anti-CD25 antibody caused a significant decrease in the number of tender and swollen joints. (c) Elevated serum IL-15 was measured in 10 out of 21 RA patients but not in controls. No correlation was observed between IL-15 and TNF-α, CD122 expression or disease activity. Conclusions. (a) Methotrexate did not alter the effects of the PRIMATIZED® anti-CD4 antibody. Changes in antibody development processes have yielded two antibodies with different functions. (b) Anti-CD25 induced decrease in CD25+ T cells was associated with clinical benefit. The exact mechanisms of action are not clear. (c) Serum IL-15 levels in RA may be a more sensitive indicator of inflammation than TNF-α and may be a valuable tool in diagnosis.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectBiology, Molecular.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectHealth Sciences, Immunology.en_US
dc.titleMonoclonal antibody therapy of rheumatoid arthritisen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest9960255en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b40274391en_US
refterms.dateFOA2018-05-27T17:13:39Z
html.description.abstractObjectives. To (a) determine the immunological effects of a PRIMATIZED® anti-CD4 antibody alone or in combination with methotrexate in RA patients, (b) determine the immunological effects of a chimeric anti-CD25 antibody in RA patients who are partially refractive to methotrexate and (c) compare interleukin-15 levels in the serum of RA patients and healthy controls and determine if there is a correlation between this cytokine and serum TNF-α, CD 122 expression, and disease activity. Patients and methods. (a) Eight RA patients were selected, four received anti-CD4+ placebo and the other four received anti-CD4+ methotrexate for 4 weeks. The immunological effects were assessed on peripheral blood by flow cytometry and thymidine incorporation assays. (b) Six RA patients were given anti-CD25 antibody (0.02-60mg) along with methotrexate for 26 days. The immunological effects were assessed on peripheral blood by flow cytometry, thymidine assays, and ELISA. (c) Blood and disease activity from twenty-one RA patients were obtained and serum IL-15 and TNF-α levels were measured by ELISA. IL-15R β chain (CD 122) expression was measured by flow cytometry. Results. (a) The anti-CD4 antibody caused a selective and significant decrease in the number of CD4+ T cells. No inhibition of PHA or mitogenic antibody stimulated proliferation was observed. (b) The anti-CD25 antibody caused a significant decrease in the percent CD25+ cells. The antibody bound CD25 and prevented interaction of IL-2 and IL-2R. Anti-CD25 antibody caused a significant decrease in PHA or mitogenic antibody stimulated proliferation. Clinically, the anti-CD25 antibody caused a significant decrease in the number of tender and swollen joints. (c) Elevated serum IL-15 was measured in 10 out of 21 RA patients but not in controls. No correlation was observed between IL-15 and TNF-α, CD122 expression or disease activity. Conclusions. (a) Methotrexate did not alter the effects of the PRIMATIZED® anti-CD4 antibody. Changes in antibody development processes have yielded two antibodies with different functions. (b) Anti-CD25 induced decrease in CD25+ T cells was associated with clinical benefit. The exact mechanisms of action are not clear. (c) Serum IL-15 levels in RA may be a more sensitive indicator of inflammation than TNF-α and may be a valuable tool in diagnosis.


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