Abstract

Different types of proteases may play influential roles across a spectrum of diseases. Correspondingly, protease inhibitors have been known to play crucial roles in the patho-physiology of diseases. We hypothesize the activity of the broad spectrum protease inhibitor, alpha-2-macroglobulin (A2M) may hold unexplored roles in diseases as well. Clinically measuring levels of variant proteases in combination with the monitoring of A2M, in plasma, can be a novel approach to further our understanding of diseases related to protease activity. There is evidence showing administration of purified human A2M to animal models with bacteria induced septic shock using Pseudomonas aeruginosa resulted in the reversal of the pathological effect. In addition, recent evidence has also shown the beneficial effects of treatment with autologous A2M in post-traumatic osteoarthritis patients. We investigated the relationship of protease activity and concentration of A2M in plasma of chronic ill patients in Bangladesh. Blood was collected to prepare plasma from patients (n=20) of different categories: severe burn, cancer of different types, enteric fever with psychosis, chronic pancreatitis, chronic liver diseases, different types of kidney diseases, different types of pulmonary diseases, diabetes and hypertension. As control, plasma was prepared from healthy volunteers (n=20) without any known disease(s). Plasma concentrations of A2M were measured by sandwich ELISA (Enzyme– Linked Immunosorbent Assay) and protease activity assay were done by protease activity assay kit. In this study, we have found that all chronically ill patients (n=20) with a verity of diseases, A2M concentration went down significantly (p<0.001) compared to the concentration of normal healthy individuals (n=20). On contrary, the protease activity level were increased significantly (p<0.001) in all chronically ill patients (n=20) compared the activity of normal healthy individuals (n=20). These results clearly indicated an inverse relationship of A2M to the protease activity in chronically ill patients in Bangladesh which may be a novel approach to further our understanding of pathophysiology of diseases related to protease activity.

Keywords: Autologous protein; Immune system; Chronic diseases; Prevention of diseases; Patho-physiology of diseases