TGFβ(1) and sCTLA-4 levels are increased in eltrombopag-exposed patients with ITP.
Some thrombopoietin receptor-agonists (TPR-As) have been developed and shown to be highly effective in the treatment of immune thrombocytopenic purpura (ITP). Soluble cytotoxic T-lymphocyte-associated antigen 4 (sCTLA-4) can modulate and terminate the immune response. Several reports have shown that sCTLA-4 levels are elevated in patients with some autoimmune disorders. However, sCTLA-4 levels have not previously been investigated in TPR-A exposed patients with ITP. We investigated the levels of transforming growth factor (TGF) β(1) and sCTLA-4 in ITP patients to determine the clinical association with TGFβ(1) and sCTLA-4 in TPR-A-exposed patients with ITP. Thirty-seven ITP patients were divided into 2 groups (TPR-A-exposed: 13 patients; unexposed: 24 patients). Doses of eltrombopag ranging from 12.5mg to 50mg were administered daily, and biochemical data obtained before and after eltrombopag administration were compared. Eltrombopag therapy significantly increased sCTLA-4 and TGFβ(1) levels relative to baseline in patients with ITP. In addition, plasma TGFβ(1) was positively correlated with platelet counts and sCTLA-4 in patients with ITP in the eltrombopag-exposed group. However, no significant change in the detection rate for anti-glycoprotein antibody was observed before and 24 weeks after eltrombopag treatment. These results suggest that eltrombopag can partially modulate some immune responses by TGFβ(1) and sCTLA-4, but it does not induce immune tolerance by 24 weeks after treatment.
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Shinya
S
Fujita
Takahisa
T
Nakanishi
Hideaki
H
Yoshimura
Masaaki
M
Hotta
Naoto
N
Nakamichi
Takeshi
T
Tamaki
Kazuyoshi
K
Ishii
Tomoki
T
Ito
Shosaku
S
Nomura
D001565:Benzoates / Q000008:administration & dosage*; D060908:CTLA-4 Antigen / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011696:Purpura, Thrombocytopenic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D011720:Pyrazoles / Q000008:administration & dosage*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D016896:Treatment Outcome
D001565:Benzoates; D060908:CTLA-4 Antigen; D006834:Hydrazines; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C520809:eltrombopag