Mucin mutations and aberrant expression are associated with the pathogenesis of immune thrombocytopenia

Abstract Purpose Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease of unknown aetiology. In this study, we aimed to identify the mutations and aberrant expression of mucins associated with ITP pathogenesis. Methods First, we investigated the DNA mutation profile of bone marrow samples from patients with ITP (n = 20) by using next-generation sequencing (NGS). In addition, MUC3A, MUC5B and MUC6 were mutated in all patients with ITP. ELISA (enzyme-linked immunoassay) was used to measure MUC3A, MUC5B and MUC6 levels in the plasma of bone marrow fluid mononuclear cells (BMMCs) and peripheral blood mononuclear cells (PBMCs). Real-time quantitative PCR was used to study the mRNA expression levels of MUC3A, MUC5B and MUC6 in BMMCs and PBMCs. Results The results indicated that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. MUC3A levels were not significantly different among the three groups, whereas MUC5B and MUC6 expression were significantly down-regulated in patients with ITP compared with healthy controls. In addition, serum MUC5B and MUC6 levels were significantly higher in patients with ITP in clinical remission than in patients with active ITP. Conclusions Taken together, these results suggest that genetic alterations and the aberrant serum expression of mucins might be involved in the pathogenesis of ITP.