Objective: To study the quantity and function of bone marrow (BM) Th17 cells in the blood cytopenia patients with positive BMMNC-Coombs test (IRP) and to explore the role of Th17 cells in the pathogenesis of the disease.
Methods: Forty-three untreated IRP patients, 34 recovered IRP patients and 13 healthy donors were enrolled in this study. The ratio of IL-23R(+)CD4(+)/CD4(+)cells in BM were examined by flow cytometry(FCM), the levels of IL-6, IL-23, IL-17 by ELISA, and the expressions of RORγt mRNA, STAT3 mRNA in BMMNC by semiquantitive RT-PCR.
Results: The ratio of IL-23R(+)CD4(+)/CD4(+)cells [(3.6 ± 3.1)%], the levels of IL-6[(26.21 ± 14.55) µg/L], IL-23[(2.23 ± 0.99) µg/L], IL-17[(2.54 ± 1.33) µg/L] and the expressions of RORγt mRNA (0.25 ± 0.08) and STAT3 mRNA (1.10 ± 0.16) in BMMNC of untreated IRP patients were significantly higher than those of recovered IRP patients[(2.0 ± 1.0)%, (9.08 ± 6.36) µg/L, (0.91 ± 0.76) µg/L, (1.28 ± 0.18) µg/L, 0.12 ± 0.08, 0.97 ± 0.12 respectively] (P < 0.05); there was no significiant difference between those of recovered IRP patients and normal controls [(1.9 ± 1.4)%, (14.63 ± 7.66) µg/L, (1.19 ± 0.98) µg/L, (1.50 ± 0.28) µg/L, 0.07 ± 0.05, 0.95 ± 0.13, respectively] (P > 0.05). In IRP group, there were significantly positive correlations between the ratios of IL-23R(+)CD4(+)/CD4(+)cells and CD5(+)CD19(+)/CD19(+) (P < 0.05), there were significantly positive correlations between the levels of IL-17 and CD5(+)CD19(+)/CD19(+), the quantity of BMMNC-antibody (r = 0.494 and 0.377, respectively) (P < 0.05); and so did between the expressions of RORγt mRNA and the ratio of CD5(+)CD19(+)/CD19(+), the quantity of BMMNC-antibody (r = 0.741 and 0.541, respectively) (P < 0.05), and between the ratio of IL-23R(+)CD4(+)/CD4(+) and the level of IL-17, the expression of STAT3 mRNA (r = 0.438 and 0.448, respectively) (P < 0.05).
Conclusions: There exists increased qunantity and hyperfunction of Th17 cells in the IRP patients which induce B cells hyperfunction and production of autoantibodies against the BM hematopoietic cells. Th17 cells might be a potential new therapeutic target of IRP.