Naturally Occurring Regulatory T Cells and Interleukins 10 and 12 in the Pathogenesis of Idiopathic Warm Autoimmune Hemolytic Anemia

Objectives: Naturally occurring regulatory T cells (nTregs) play an important role in immunologic tolerance and control immune-mediated pathology in murine models of autoimmune hemolytic anemia. Our aim was to measure nTregs and levels of interleukin (IL) 10 and IL-12 in peripheral blood mononuclear cell (PBMC) cultures from patients with idiopathic warm autoimmune hemolytic anemia (wAIHA) in an attempt to unravel some of the mysteries behind the pathogenesis of this autoimmune disorder. Methods: Twenty-seven patients with idiopathic wAIHA and 15 age- and sex-matched controls underwent flow cytometric analysis of CD4(+)CD25(high)FoxP3(+)T cells (nTregs) and analysis by enzyme-linked immunosorbent assay of IL-10 and IL-12 in the supernatants of basal and lipopolysaccharide (LPS)-stimulated PBMC cultures. Results: The mean (SD) percentage of circulating CD4(+) nTregs in peripheral blood was significantly lower in patients (4.63\%{[}1.0\%]) than in controls (9.76\% {[}0.78\%]) (P<.001). PBMCs from patients had significantly higher basal levels of IL-10 and IL-12, with a dramatic reduction in responsiveness to LPS in vitro compared to controls. There was a significantly negative correlation between the percentage of nTregs and reticulocyte count (RC), basal IL-10, and LPS-stimulated IL-10, and a significantly positive correlation with haptoglobin (Hp) (P<.05). Basal IL-10 and LPS-stimulated IL-10 were positively correlated with RC (P<.001 in both cases) and negatively correlated with Hp (P<.01 and P<.05, respectively). Conclusion: Our study indicates that a reduced percentage of nTregs and IL-10/1L-12 imbalance may play an essential role in the onset and/or maintenance of this AIHA.