DEFECTIVE IRON SUPPLY FOR ERYTHROPOIESIS AND ADEQUATE ENDOGENOUS ERYTHROPOIETIN PRODUCTION IN THE ANEMIA ASSOCIATED WITH SYSTEMIC-ONSET JUVENILE CHRONIC ARTHRITIS

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with h igh levels of circulating interleukin-6 (IL-6) and is frequently compl icated by severe microcytic anemia whose pathogenesis is unclear. Ther efore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) l evels < 12 g/dL, evaluating erythroid progenitor proliferation, endoge nous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb lev el was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001), suggesting that the severity of anemia was directly proport ional to the degree of iron-deficient erythropoiesis. Serum ferritin r anged from 18 to 1,660 mu g/L and was unrelated to Hb level. Bone marr ow iron stores were markedly reduced in the three children investigate d, and they also showed increased serum transferrin receptor and norma l-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropo ietin (epo) production was appropriate for the degree of anemia as jud ged by both the observed to predicted log (serum epo) ratio (0.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these s ubjects with that of thalassemiapatients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transfe rrin receptor explained 61% of the variation i n Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intra venous iron administration resulted in normalization of serum transfer rin receptor. Defective iron supply to the erythron rather than blunte d epo production is the major cause of the microcytic anemia associate d with SoJCA. A true body-iron deficiency caused by decreased iron abs orption likely complicates long-lasting inflammation in the most anemi c children, and this can be recognized by high serum transferrin recep tor levels. Although oral iron is of no benefit, intravenous iron sacc harate is a safe and effective means for improving iron availability f or erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, the y are probably responsible for the observed abnormalities in iron meta bolism. Anemia of chronic disease encompasses a variety of anemic cond itions whose peculiar features may specifically correlate with the typ e of cytokine(s) predominantly released. (C) by The American Society o f Hematology