Peripheral monocytes and CD4⁺ cells are potential Sources for increased circulating levels of TGF‐β and substance P in autoimmune myelofibrosis

Abstract

Myelofibrosis is an uncommon phenomenon associated with a variety of neoplastic and inflammatory processes. Although there is evidence that cytokines elaborated by clonal malignant hematopoietic cells are implicated in myelofibrosis in primary hematologic disorders, there has been little data to date on the pathophysiology of myelofibrosis in autoimmune disorders. Here we report a case of autoimmune myelofibrosis with pancytopenia. Peripheral blood monocytes and CD4-positive lymphocytes produced significantly elevated levels of transforming growth factor b (TGF-b) compared to similar cells from healthy volunteer controls. TGF-b has been implicated in the pathogenesis of myelofibrosis associated with primary hematological malignancies. Furthermore, substance P, previously linked to myelofibrosis, was also detected in elevated levels in the patient's serum and correlated negatively with the levels of the patient's blood counts. These findings suggest a role for both TGF-b and substance P in the pathophysiology of autoimmune myelofibrosis. This is the first report of deregulated production of TGF-b by monocytes in the pathobiology of autoimmune myelofibrosis. Am.

Autoimmune Myelofibrosis Accompanied by Sjögren's Syndrome in a 47, XXX/46, XX Mosaic Woman

“…In the present case, reticulin fibrosis was present in the marrow, and there were lymphocytic infiltrates and aggregates composed There are few data regarding the pathophysiology of myelofibrosis in patients with autoimmune disorders. Harrison et al reported a case of AIMF with pancytopenia in which peripheral blood monocytes and CD4-positive lymphocytes produced significantly elevated levels of transforming growth factor β (TGF-β), compared to that observed in similar cells obtained from healthy volunteer controls (9). Furthermore, substance P was also detected at an elevated level in the patient's serum and was found to be negatively correlated with blood counts.…”

“…2). A chromosomal analysis of peripheral blood lymphocytes demonstrated findings of 47, XXX [21]/46, XX [9]. Therefore, the chromosomal anomaly was congenital, and the patient was considered to be a 47, XXX/46, XX mosaic woman.…”

Cord Blood Transplantation Provided Long-term Remission in a Case of Adult T-cell Leukemia-lymphoma (ATL) with Myelofibrosis

“…Several cytokines, such as TGF-β1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (b-FGF), have been reported to stimulate fibrotic changes in the bone marrow (3,23). CD4-positive lymphocytes of patients with peripheral T-cell lymphoma and autoimmune disease have been reported to produce TGF-β1, leading to the formation of MF (7,24). In our case, persistent MF and elevated serum TGF-β1 levels were observed even after the reduction of CD4-positive lymphocytes by chemotherapy.…”

Primary autoimmune myelofibrosis in a 36-year-old patient presenting with isolated extreme anemia

“…It probably involves the production of fibrogenic cytokines (such as transforming growth factor-β and the peptide substance P) by inflammatory cells [9]. The primary treatment of AIMF is corticosteroids [3, 7], with most patients having a rapid response in cytopenias but usually mild or no improvement in myelofibrosis [3].…”