Elevated Dipeptidyl Peptidase IV (DPP-IV) Activity in Plasma from Patients with Various Lysosomal Diseases.

Agnieszka Ługowska,Małgorzata Bednarska-Makaruk,Jolanta Kubalska,Jolanta Wierzba,Barbara Perkowska-Sumiła,Ekaterina Zakharova,Hanna Mierzewska,Galina Baydakova,Tomasz Kmieć,Krystyna Szymańska,Alex Ilyushkina,Ałła Graban,Anna Tylki-Szymańska

doi:10.3390/diagnostics11020320

Abstract

Increased activity of dipeptidyl peptidase IV (DPP-IV) was reported earlier in patients with different types of mucopolysaccharidoses. DPP-IV (also known as CD26 lymphocyte T surface antigen) is a transmembrane protein showing protease activity. This enzyme displays various functions in the organism and plays an important role in multiple processes like glucose metabolism, nociception, cell-adhesion, psychoneuroendocrine regulation, immune response and cardiovascular adaptation. In order to evaluate DPP-IV in lysosomal storage diseases (LSD), we examined its activity in plasma samples from 307 patients affected with 24 different LSDs and in 75 control persons. Our results revealed elevated DPP-IV activity especially in individuals affected with mucolipidosis II/III, alpha-mannosidosis, and mucopolysaccharidoses types III, II, and I (p < 0.05). In other LSDs the DPP-IV activity was still significantly increased, but to a lesser extent. In patients with Gaucher disease, ceroid lipofuscinosis type 1 (CLN1), Niemann–Pick disease type C and A, Krabbe and Pompe diseases, gangliosidosis GM2 and metachromatic leukodystrophy discreet or no changes in DPP-IV activity were observed. DPP-IV may serve as a first-tier diagnostic procedure or additional biochemical analysis in recognizing patients with some LSDs. DPP-IV may become an object of basic research for a better understanding of LSDs.

Highlights

Lysosomal storage diseases (LSDs) belong to a group of inherited metabolic disorders with a frequency ranging from about 1 in 4000 to 1 in 13,000 live births [1,2,3,4]
Due to the fact that some LSDs are treated with enzyme replacement therapy (ERT), substrate reduction therapy (SRT), pharmacological chaperones or hematopoietic stem cell transplantation (HSCT), there is a special need for quick diagnostic procedure and a tool for monitoring of LSD therapy
Screening for the dipeptidyl peptidase IV (DPP-IV) activity in plasma samples from patients with different lysosomal diseases (LSDs) revealed elevated activity of this enzyme, especially in individuals affected with mucolipidosis II/III, alpha-mannosidosis and mucopolysaccharidoses types III, II and I

Summary

Introduction

Lysosomal storage diseases (LSDs) belong to a group of inherited metabolic disorders with a frequency ranging from about 1 in 4000 to 1 in 13,000 live births [1,2,3,4]. Due to the fact that some LSDs are treated with enzyme replacement therapy (ERT), substrate reduction therapy (SRT), pharmacological chaperones or hematopoietic stem cell transplantation (HSCT), there is a special need for quick diagnostic procedure and a tool for monitoring of LSD therapy. In this aspect, biomarkers seem to play an important role, since they enable neonatal or selective screening, can serve as an additional diagnostic parameter or can be used for monitoring of treatment efficacy

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