Lysosome-related proteins may have changes in the urinary exosomes of patients with acute gout attack.

Abstract

Background: The autophagy-lysosome is intricately linked to the development of gout. At present, the diagnosis and monitoring of gout are mainly invasive tests, which cannot predict the occurrence of gout in the acute phase, and bring new pain to patients. This study focuses on the changes of lysosome-related proteins in urinary exosomes of patients with acute gout attack to explore the potential noninvasive biomarkers clinical application value.

Methods: Urine samples were collected from the subject and exosomes were extracted. To explore the differentially expressed proteins in urinary exosomes among acute gout patients (AD group), intermittent gout patients (ID group) and normal controls (NC group) by DIA mass spectrometry. Urinary exosomal lysosome associated proteins were analyzed and receiver operating characteristic (ROC) curves of differentially expressed proteins were drawn to evaluate their clinical value in monitoring acute gout attack.

Results: A total of 1896 proteins were detected between AD group and ID group, of which 121 proteins were differentially expressed (FC > 1.5 and p < 0.05). There were three lysosomal-related proteins differentially expressed in urinary exosomes between AD group and ID group. Compared with the ID group, the expression of Cathepsin Z (CTSZ) and AP-1 complex subunit beta-1 (AP1B1) was increased, while the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2) was decreased in AD group. The ROC analysis showed that CTSZ, AP1B1 and LAMP2 had a strong ability to predict acute gout attack, with AUC of 0.826, 0.847 and 0.882, respectively.

Conclusions: There are many specific protein changes in the urinary exosomes of patients with acute gout attack. The urinary exosomes of patients with acute gout attack may exhibit alterations in lysosome-related proteins, particularly CTSZ, AP1B1, and LAMP2, which may become potential biomarkers for monitoring acute gout attack.