Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Abstract

AimsAnaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subsequent to diminished erythropoiesis as a result of an immune-mediated suppression of erythroid colony formation. MethodsWe studied 61 CHF patients and 20 healthy control subjects. Circulating primitive haematopoietic (CD34+) and erythroid precursor cells were quantified by flow cytometry. Circulating erythroid progenitors (BFU-E) were cultured in methylcellulose in the presence and absence of monocytes and sera, and with anti-TNFα neutralising antibodies. ResultsDespite higher erythropoietin levels, anaemic patients exhibited lower absolute reticulocyte counts and reticulocyte production indices (P<0.001) than non-anaemic patients and healthy controls. Diminished erythropoiesis was paralleled by attenuated circulating CD34+, erythroid progenitor and precursor cells in anaemic patients (all P<0.01). Depletion of monocytes from cultures derived only from anaemic patients enhanced BFU-E growth (P=0.03). Only the addition of monocytes and sera from anaemic patients suppressed autologous or allogeneic BFU-E colony formation (P=0.02). Serum TNFα levels were highest in anaemic patients and anti-TNFα neutralising antibodies partly abrogated the inhibitory effects of anaemic sera on erythroid colony growth (P=0.03). ConclusionUnexplained anaemia in patients with CHF results partly from suppressed erythropoiesis and monocytes, via a direct effect of TNFα on erythroid cells, orchestrate a degree of this suppression.