Premium
Reduced TGF‐β1 in patients with aplastic anaemia in vivo and in vitro
Author(s) -
Rizzo S.,
Killick S. B.,
Patel S.,
Ball S. E.,
Wadhwa M.,
Dilger P.,
GordonSmith E. C.,
Gibson F. M.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01761.x
Subject(s) - bone marrow , cytokine , aplastic anemia , medicine , stromal cell , haematopoiesis , peripheral blood mononuclear cell , stem cell , endocrinology , immunology , biology , in vitro , biochemistry , genetics
Transforming growth factor β (TGF‐β) 1 is a ubiquitous bifunctional cytokine implicated in the regulation of haemopoietic stem cells and bone marrow stromal cells. We analysed sera from 63 patients with aplastic anaemia and describe a significant reduction of TGF‐β1 that was directly related to their treatment status. Untreated patients ( n = 35), patients who did not respond ( n = 15) and those with a partial response ( n = 23) to treatment had significantly lower TGF‐β1 than the normal control group ( n = 55), P < 0.0001, P < 0.0001 and P = 0.002 respectively. Patients in complete remission ( n = 15) exhibited TGF‐β1 serum levels comparable to the control group. In addition, there was a correlation ( r = 0.83, P < 0.0001) between serum TGF‐β1 and platelet count at time of sample. We have demonstrated that the primary source of TGF‐β1 in peripheral blood mononuclear cell (PBMC) cultures was not CD3‐positive cells. These data indicate aplastic anaemia is associated with a decreased TGF‐β1 expression in peripheral blood circulation, which may be a direct consequence of thrombocytopenia. In vitro stromal layers grown from aplastic patient bone marrow ( n = 14) produced significantly lower levels of TGF‐β1 ( P = 0.02) when compared to normal stroma ( n = 15). In the aplastic anaemia bone marrow compartment we postulate that accessory cells down‐regulate TGF‐β1 expression to allow stem cell cycling to counteract hypoplasia. As TGF‐β1 is important in the regulation of haemopoiesis, dysregulation of this cytokine in combination with previously described abnormal cytokine expression may contribute significantly to the pathophysiology of aplastic anaemia by exacerbating primary stem cell defects.