Lower level of IL-35 and its reduced inhibition in Th17 cells in patients with bone marrow mononuclear cells Coombs test-positive hemocytopenia

摘要

Interleukin (IL)-35 is the latest member of IL-12 family, which plays an important role in other autoimmune diseases. Bone marrow mononuclear cells Coombs test-positive hemocytopenia, also termed immunorelated hemocytopenia (IRH) is a type of autoimmune-associated diseases. The present study investigated the relationship of IL-35 in patients with IRH. A total of 43 patients with IRH and 19 normal controls were enrolled in the current study. Serum levels of IL-35 and IL-17 in peripheral blood were evaluated by ELISA. Regulatory T cells (Tregs) level was detected by flow cytometry and IL-35 subunits mRNA in Treg was determined using reverse transcription-quantitative polymerase chain reaction: Epstein-Barr virus induced 3 (EBI3) and IL-12α chain p35. Effect of IL-35 on T helper 17 cells (Th17) cells was determined by mix-culture of IL-35 with CD4⁺ T lymphocytes. Serum level of IL-35 was decreased in untreated patients with IRH compared with remission patients (P<0.01) and was significantly associated with clinical indexes. Frequency of IL-35 produced Tregs was lower and IL-35 subunits mRNA in CD4⁺CD25⁺ Tregs were decreased in patients with IRH compared with health controls (P<0.01). Serum level of IL-17 was increased in patients with IRH (P<0.01) and there was a negative correlation between IL-35 and IL-17 (r=−0.553; P<0.01). The production of Th17 cells and IL-17A mRNA expression were reduced (P<0.05) after mix-culture of CD4⁺ T lymphocytes with IL-35 compared with mix-culture of CD4⁺ T lymphocytes without IL-35. In conclusion, the present study revealed that IL-35 may be a monitoring indicator of IRH occurrence and progression. IL-35 level was lower and the inhibition on Th17 cells was reduced in the patients with IRH.