Immune correlates of steroid responsiveness in ITP

University Of Pennsylvania, Philadelphia PA

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Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Each year millions of people in the United States take steroids (glucocorticoids) under the direction of their physicians. Oral steroids are a standard first-line therapy for autoimmune disorders such as immune thrombocytopenia (ITP). Patients with ITP suffer from antibody-mediated destruction of platelets and can have life-threatening bleeding. As physicians, we do not know how long to give steroids for ITP or at what dose and we do not understand why they work to quiet the immune system in some patients but not in others. Herein we propose to perform ancillary studies on circulating lymphocytes of human subjects who are enrolled in the ITP^2 study, a randomized clinical trial designed to compare prednisone to dexamethasone for the treatment of newly diagnosed ITP. Approximately 50% of new ITP patients appear to have a lasting response to dexamethasone whereas only 5-15% of ITP patients respond similarly to oral prednisone. In order to gain insights into the basis of the immune defect in ITP, why dexamethasone appears to work better than prednisone and why only some patients respond to steroids, we will: 1. determine if dexamethasone yields a different response from prednisone in B and T lymphocyte subsets over time;2. determine if steroid non-responders are more likely to have complex lymphocyte defects or fail to re-set their antibody repertoire or both and 3. use flow cytometric fingerprinting analysis and quantitative mass spectrometry to compare candidate biomarkers in B cells of ITP patients who respond vs. those who fail to respond to steroid therapy. These studies will teach us about the nature of lymphocyte defects in new-onset ITP, provide insights into how steroids work in ITP and potentially yield biomarkers of steroid responsiveness. These studies are relevant not only to ITP, but potentially also to a much larger range of autoimmune and inflammatory conditions for which steroids are administered. This is a study of the immune defects that underlie primary immune thrombocytopenia (ITP) in adults. The study may also improve our understanding of how prednisone and dexamethasone influence lymphocyte subsets and B cell repertoire and may result in the identification of biomarkers that predict steroid responsiveness. These findings may help guide therapy in future patients with ITP as well as potentially in patients with other autoimmune or inflammatory conditions.