Urine proteome uncover common mechanism between mucopolysaccharidosis type I and II

Abstract

Abstract Mucopolysaccharidosis (MPS) type I and II are two types of rare lysosomal storage diseases, which lead to the accumulation of glycosaminoglycans due to the lack of the enzyme alpha-L-iduronidase (IDUA) and iduronate 2-sulfatase (IDS) respectively. There are some similar pathogenic mechanisms and clinical phenotypes but also some specific minute manifestations between these two subtypes. To better understand the similarities in the pathogenesis and clinical symptoms of these two diseases and the mechanism of differential symptoms, we used TMT technology to analyze the differential protein profiles in the urine of MPS I and MPS II patients. We detected the differential proteins of MPS I and MPS II compared with the control group separately. After that, we focused on 227 differentially expressed proteins (DEPs) which showed consistent changes in the urine of both MPS I and MPS II. Parallel reaction monitoring (PRM) analysis verified that up-regulated HEXB and down-regulated HBA1 showed significant difference in the urine of both subtypes. In addition, we found 391 DEPs by comparative analysis of MPS I and MPS II proteomes and found that DHRS2 contributed to the difference between the two subtypes by PRM verification. Therefore, our study demonstrates the value of multi-sample proteomics combined analysis in exploring the similarities and differences of functional proteins between MPS I and MPS II, which provides a new idea for the clinical study of the characteristics of MPS subtypes and the exploration of common treatment options.