Shih-Chung Wang1, Kuender D Yang2,3, Ching-Yuang Lin4,5, Alex Y Huang6, Chien-Chou Hsiao1,7,8, Ming-Tsan Lin1, Yi-Giien Tsai1,7,8. 1. Division of Pediatric Hematology-Oncology, Department of Pediatrics, Changhua Christian Children's Hospital, Changhua City, Taiwan. 2. Mackay Children's Hospital, and Institute of Biomedical Sciences, Mackay Medical College, Taipei, Taiwan. 3. Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan. 4. Clinical Immunological Center, China Medical University Hospital, Taichung, Taiwan. 5. Division of Pediatric Nephrology, Childrens' Hospital, China Medical University, Taichung, Taiwan. 6. Division of Pediatric Hematology-Oncology, Department of Pediatrics, UH Rainbow Babies and Children's Hospital; Case Western Reserve University School of Medicine, Cleveland, Ohio. 7. School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 8. School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
BACKGROUND: This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. METHODS: We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 109 /L at 12 months after IVIG treatment. RESULTS: Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. CONCLUSIONS: Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.
BACKGROUND: This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. METHODS: We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 109 /L at 12 months after IVIG treatment. RESULTS:Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. CONCLUSIONS: Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.