Gascón P, Sathe S S, Rameshwar P
Division of Hematology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
Am J Med. 1993 Jan;94(1):41-8. doi: 10.1016/0002-9343(93)90118-9.
Anemia is an important negative predictor for survival with disseminated Mycobacterium avium complex (MAC) infection in the acquired immunodeficiency syndrome (AIDS). We analyzed the differences in AIDS patients with and without MAC infection with regard to anemia, severity of human immunodeficiency virus (HIV) infection, bone marrow morphology, and bone marrow erythroid progenitor colony growth (BFU-E and CFU-E). In addition, we determined the in vitro effect of sera obtained from these patients on normal BFU-E and CFU-E. A possible role of macrophages in the suppression of erythropoiesis was examined by studying in vitro the effect of supernatants from MAC-infected macrophages on cultured BFU-E and CFU-E.
Hematocrit, serum levels of p24 antigen, erythropoietin, and CD4-positive cell count were determined in 14 AIDS patients with and 24 without MAC infection. Bone marrow erythropoietic and granulocytic progenitor cells from 15 normal individuals, from 12 AIDS patients with MAC infection, and from 10 AIDS patients without MAC infection were cultured on methylcellulose. In addition, progenitor cells from normal individuals were cultured in the presence, and in the absence, of sera obtained from AIDS patients with (14), or without (24), MAC infection. Last, we studied the effect of supernatants (SNs) from MAC and Mycobacterium tuberculosis-infected macrophages on erythropoietic progenitor cell growth.
The anemia in AIDS patients with MAC infection was associated with a selective suppression of erythropoietic progenitors despite bone marrow morphology that was indistinguishable from that in patients without MAC infection. The degree of anemia could not be explained on the basis of severity of HIV infection or a deficiency of erythropoietin production. Bone marrow mononuclear cells from AIDS patients with MAC generated significantly fewer erythroid progenitor colonies (BFU-E and CFU-E) than equivalent cells from AIDS patients without MAC infection (p < 0.05). Sera from MAC-infected AIDS patients were markedly inhibitory to the erythroid progenitors as compared with sera from patients without MAC infection (p < 0.001). SNs from MAC-infected macrophages were markedly inhibitory to the erythroid progenitors (BFU-E and CFU-E) as compared with the myeloid progenitors (CFU-GM).
The profound anemia in MAC-infected AIDS patients is due to suppression of erythroid progenitors by a soluble factor(s) in the serum. The data suggest that the soluble factor(s) is probably elaborated by macrophages.
贫血是获得性免疫缺陷综合征（AIDS）患者播散性鸟分枝杆菌复合体（MAC）感染生存的重要负面预测指标。我们分析了合并和未合并MAC感染的AIDS患者在贫血、人类免疫缺陷病毒（HIV）感染严重程度、骨髓形态以及骨髓红系祖细胞集落生长（爆式红系集落形成单位[BFU-E]和红系集落形成单位[CFU-E]）方面的差异。此外，我们测定了这些患者血清对正常BFU-E和CFU-E的体外作用。通过体外研究MAC感染巨噬细胞的上清液对培养的BFU-E和CFU-E的作用，探讨了巨噬细胞在抑制红细胞生成中的可能作用。
测定了14例合并MAC感染和24例未合并MAC感染的AIDS患者的血细胞比容、p24抗原血清水平、促红细胞生成素及CD4阳性细胞计数。将15名正常个体、12例合并MAC感染的AIDS患者和10例未合并MAC感染的AIDS患者的骨髓红系和粒系祖细胞在甲基纤维素上进行培养。此外，将正常个体的祖细胞在有或无合并（14例）或未合并（24例）MAC感染的AIDS患者血清存在的情况下进行培养。最后，我们研究了MAC和结核分枝杆菌感染巨噬细胞的上清液（SNs）对红系祖细胞生长的影响。
合并MAC感染的AIDS患者的贫血与红系祖细胞的选择性抑制有关，尽管其骨髓形态与未合并MAC感染的患者无明显差异。贫血程度不能用HIV感染严重程度或促红细胞生成素产生不足来解释。合并MAC感染的AIDS患者的骨髓单个核细胞产生的红系祖细胞集落（BFU-E和CFU-E）明显少于未合并MAC感染的AIDS患者的同等细胞（p<0.05）。与未合并MAC感染患者的血清相比，合并MAC感染的AIDS患者的血清对红系祖细胞有明显抑制作用（p<0.001）。与髓系祖细胞（CFU-GM）相比，MAC感染巨噬细胞的SNs对红系祖细胞（BFU-E和CFU-E）有明显抑制作用。
合并MAC感染的AIDS患者的严重贫血是由于血清中的一种或多种可溶性因子抑制了红系祖细胞。数据表明，这种可溶性因子可能是由巨噬细胞产生的。
