Bone marrow and peripheral blood HLA-G in hematologic diseases presenting with impaired erythropoiesis

The HLA-G molecule is expressed in few tissues and cells, such as erythroid precursors, in which it has been associated with cell signaling, maturation, and proliferation. Considering that the daily production of erythrocytes is massive, the bone marrow sHLA-G levels are higher than in peripheral plasma, and little attention has been devoted to the role of HLA-G in disorders presenting with defective erythropoiesis, we hypothesized that bone marrow could be a major source of sHLA-G to plasma. We investigated HLA-G (soluble-sHLA-G and membrane-bound) in patients presenting hematologic disorders with impaired erythropoiesis (n = 61, including myeloproliferative neoplasm-MPN, myelodysplastic neoplasm-MDS, aplastic anemia-AA, inherited bone marrow failure-BMF, secondary erythrocytosis-SE), and in healthy individuals. Indeed, sHLA-G levels (ELISA) in bone marrow of healthy individuals were higher compared to patients (p < 0.001), and we observed an overall positive correlation between bone marrow and peripheral blood sHLA-G (p < 0.05). The logistic regression showed that the lower sHLAG plasma bone marrow levels the greater the probability of developing impaired erythropoiesis (p < 0.001). In MDS patients and controls, HLA-G (flow cytometry) was expressed on myeloid precursor cells, followed by erythroid precursors and proerythroblasts, and was not expressed on differentiated erythroid cells. The use of recombinant erythropoietin (rEPO) in MDS patients (n = 3) increased the expression of HLA-G in myeloid precursors, in which HLA-G was normally expressed. Decreased bone marrow sHLA-G level is a shared feature among patients with impaired erythropoiesis and rEPO may increase HLA-G cell expression in MDS patients, corroborating the role of HLA-G along erythrocyte development.