Evaluation of Stroma in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome–Affected Bone Marrows and Correlation With CD4 Counts

Abstract

Little is known about cellular and extracellular composition of fibrosis in bone marrows in the context of human immunodeficiency virus/acquired immunodeficiency syndrome. To evaluate the stromal composition of bone marrows affected by human immunodeficiency virus/ acquired immunodeficiency syndrome and to correlate this with laboratory parameters including CD4 lymphocyte counts. We evaluated extracellular matrix and stromal cell composition in bone marrows and correlated these results with hematologic parameters. Extracellular matrix, stromal cells, and smooth muscle differentiation were evaluated by immunohistochemistry for collagen type IV expression and reticulin staining, an antibody directed against low-affinity nerve growth factor receptor (a marker of adventitial reticular cells), and actin staining, respectively. Concurrent laboratory information was collected, including white blood cell count, hemoglobin, platelet count, CD4 count, CD8 count, CD4/CD8 ratio, and absolute lymphocyte count. Bone marrows of 35 patients with human immunodeficiency virus/acquired immunodeficiency syndrome were evaluated. Correlation of reticulin, low-affinity nerve growth factor receptor, actin, and collagen IV staining with hematologic parameters. More than half of the bone marrows showed moderate to severe reticulin fibrosis. The degree of reticulin fibrosis was correlated with the degree of low-affinity nerve growth factor receptor expression (P = .048). Actin expression was identified in only 3 of 35 cases and collagen IV in only 5 of 35 cases. No statistical relationship between degree of fibrosis and CD4 count was identified. Lower levels of low-affinity nerve growth factor receptor expression were associated with CD4 counts of >100 (P = .04). Marrow fibrosis was present in almost all cases studied (97%), and the staining of adventitial reticular cells correlated with the degree of reticulin fibrosis. There does not appear to be a correlation between CD4 count and degree of fibrosis, suggesting that the mechanism of fibrosis is independent of disease status.