Ultrastructure of the bone marrow in HIV infection: evidence of dyshaemopoiesis and stromal cell damage.

The ultrastructure of bone marrow cells was studied in nine patients infected with the human immunodeficiency virus (HIV). Two of these (cases 1 and 3) were thrombocytopenic, had never suffered from opportunistic infections and had not received any drugs prior to the time of study. A number of ultrastructural abnormalities were found in a variable proportion of the affected cell types in all nine patients. These were: (a) an increased prevalence of multivesicular bodies within several cell types and of abnormalities of the nuclear membrane in neutrophil granulocytes, (b) an increase in the size of the Golgi apparatus and in the quantity of endoplasmic reticulum in neutrophil granulocytes, (c) dysplastic features, including multiple long intranuclear clefts and large cytoplasmic vacuoles in some erythroblasts and (d) vacuolation of the plasma cells. Other abnormalities seen in a proportion of the patients were: (a) cylindrical confronting cisternae (CCC) in some of the lymphocytes, macrophages (phagocytic reticular cells), non-phagocytic reticular cells (including adventitial cells) and endothelial cells of marrow sinusoids, (b) tubuloreticular structures (TRS) in some lymphocytes, plasma cells, monocytes and endothelial cells and (c) precipitates of protein within occasional erythroblasts and marrow reticulocytes. There was also a striking and hitherto undescribed abnormality of the structure of the nucleus in intersinusoidal and perisinusoidal non-phagocytic reticular cells. This was seen in six patients, including case 3, and was characterized by the extensive detachment of masses of abnormally electron-dense heterochromatin from the nuclear membrane, the presence of a uniformly thin layer of electron-dense material at the inner surface of the areas of nuclear membrane denuded of heterochromatin masses and an abnormal electron lucency of areas containing euchromatin. The CCC and TRS were found in the six patients with the lowest number of circulating CD4-positive T cells. The precipitation of protein within erythroid cells may have been caused by the oxidant effect of dapsone or high doses of co-trimoxazole. The abnormalities in the stromal cells and in particular the nuclear changes seen in the non-phagocytic reticular cells support the possibility that one of the mechanisms underlying the cytopenia in patients infected with HIV may be a disturbance of the microenvironmental regulation of haemopoiesis.