IMMUNE PATHOPHYSIOLOGY OF ACQUIRED APLASTIC-ANEMIA

Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anaemias, with the majority of patien ts responding to immunosuppressive therapy. In vitro, interferon (IFN) and tumour necrosis factor (TNF) inhibit haematopoiesis, including co lony formation by early and late progenitor cells and the generation o f long-term culture initiating cells (LTCIC). These lymphokines induce Fas antigen expression on CD34(+) cells and apoptosis within the haem atopoietic cell compartment. Local secretion of cytokines is far more potent than addition to long-term bone marrow cultures. Activated cyto toxic lymphocytes, high levels of INF gamma and TNF alpha, and increas ed Fas expression an CD34(+) marrow cells are present in patients. Hae matopoiesis is severely diminished in severe aplastic anaemia on prese ntation: CD34(+) cell numbers, colony forming cells and LTCIC are all markedly decreased. LTCIC numbers do not predict recovery. Blood cell counts increase in some cases in the absence of changed numbers of LTC IC, but recovered patients have higher and sometimes normal LTCIC numb ers. The mechanism by which chemical and biological agents incite alte red immunity remains unclear. Drug associations have been inferred fro m case reports and formal epidemiological studies, but have remained r efractory to systematic laboratory study. Whatever the initial events, immune system destruction of haematopoiesis plays a central role in t he development of acquired aplastic anaemia.