title: Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.
abstract: Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with both accelerated platelet destruction and impaired platelet production. We and others have described impaired regulatory CD4(+)CD25(hi) T cells (Treg) numbers and/or suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients, but information on the immunologic responses of treated patients are lacking. We studied the immunologic profile of chronic ITP patients before (n = 10) and during treatment with thrombopoietin receptor (TPO-R) agonists (n = 9). Treg activity, as measured by suppression of proliferation of autologous CD4(+) CD25(-) cells, was improved in patients on treatment (P < .05), and the improvement correlated with reduction in interleukin-2-producing CD4(+) cells, consistent with dampening of immune responses. There was a concomitant increase in total circulating transforming growth factor-β1 (TGF-β1) levels (P = .002) in patients on treatment, and the levels of TGF-β1 correlated with the degree of improvement in platelet counts (r = .8, P = .0002). This suggests that platelets in patients on TPO-R treatment may play a role in improving Treg function, either directly or indirectly by enhanced release of TGF-β1 as a result of greater platelet turnover. In conclusion, our findings suggest that thrombopoietic agents in patients with ITP have profound effects to restore immune tolerance.
authors.affiliation: Laboratory of Complement Biology, New York Blood Center, New York, NY, USA.
authors.forename: Weili
authors.initials: W
authors.lastname: Bao
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Susanne
authors.initials: S
authors.lastname: Heck
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.forename: Marissa
authors.initials: M
authors.lastname: Karpoff
authors.forename: Nayla
authors.initials: N
authors.lastname: Boulad
authors.forename: Karina
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology; D023201:CD40 Ligand / Q000097:blood; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000276:immunology*; D034061:Thrombopoiesis / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D055815:Young Adult
chemical_list: D053628:Receptors, Thrombopoietin; D053773:Transforming Growth Factor beta1; D023201:CD40 Ligand