α 1-Acid glycoprotein as a putative biomarkerfor monitoring the development of the type II reactional stage of leprosy

Abstract

Leprosy, a spectral disease manifested on the basis of host immune responses, is complicated by its reactional stages, namely type I reversal reaction (RR) and type II erythema nodosum leprosum (ENL). These reactional stages are characterized by uncontrolled and aberrant immune responses. Biomarkers for reactional stages would aid in early diagnosis, efficient treatment, prevention of neurological complications and prediction of predisposition to reactional stages. In this study, comparative analysis of the serum proteome of leprosy patients by two-dimensional electrophoresis (2DE) followed by mass spectrometry showed differential expression of acute-phase protein alpha (1)-acid glycoprotein (AGP; also known as orosomucoid). AGP levels in untreated ENL cases were significantly higher than in lepromatous leprosy (LL; a non-reactional disease stage) (P=0.0126), RR (P=0.0176) and healthy controls (P=0.0030). These data were confirmed using ELISA. The levels of AGP decreased to normal levels after treatment with multidrug therapy and thalidomide (P =0.0167). In a follow-up study, AGP levels, which were high in the untreated ENL stage, decreased significantly at 5 days ( P=0.0084) and 21 days (P=0.0027) post-treatment. A stage-dependent increase in AGP in an LL patient who progressed into the ENL stage was also shown. Glycosylation analysis by 2DE showed differential expression of acidic glycoforms of AGP in untreated ENL cases. Changes in AGP concentration and differential expression of isoforms correlated with the inflammatory condition in ENL and also with the treatment regimen. Thus, initial validation of AGP as an ENL-specific biomarker and treatment indicator was shown in this study.

Gene Set Signature of Reversal Reaction Type I in Leprosy Patients

“…For example, alpha-1-acid glycoprotein (AGP), encoded by the ORM1 gene, is a potent inhibitor of neutrophil chemotaxis and superoxide anion generation [32]. The serum level of AGP is used as a biomarker of leprosy type-2 reactions and Crohn's Disease management [33], [34]. Elafin, coded by PI3 , can effectively de-activate neutrophil elastase thus preventing excessive tissue damage [35].…”

Pathogen Induced Changes in the Protein Profile of Human Tears from Fusarium Keratitis Patients

“…Proteomics is a valuable approach to find patterns of protein markers for a given disease [21]. Gel based proteomic approach has been used to show the alterations induced at the post translational level in an infectious disease [22], [23]. Proteomic analysis can provide insights about protein expression patterns, which are associated with various pathological conditions and the identification of those tear proteins and their posttranslational modifications have the potential to reveal the mechanism of the disease [19], [24]–[28].…”

Biomarker Discovery by Novel Sensors Based on Nanoproteomics Approaches

“…Another study identified differentially expressed proteins by MALDI-TOF and MALDI-TOF-MS/MS of leprosy patients and healthy individuals [70]. A significant increase in one of the isoforms of 2α chain of haptoglobin was determined in leprosy patients.…”