title: alpha1-acid glycoprotein as a putative biomarker for 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.
authors.affiliation: Department of Genetic Engineering, School of Biotechnology,Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India.
authors.forename: Nishma
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Voluntary Health Services, Leprosy Project, Shaktinagar,Erode 638315, Tamil Nadu, India.
authors.forename: Nallakandy P
authors.initials: NP
authors.lastname: Shankernarayan
authors.affiliation: Department of Genetic Engineering, School of Biotechnology,Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India.
authors.forename: Kuppamuthu
authors.initials: K
authors.lastname: Dharmalingam
mesh_terms: D015415:Biomarkers; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D004893:Erythema Nodosum / Q000097:blood / Q000175:diagnosis*; D006031:Glycosylation; D006801:Humans; D015440:Leprosy, Lepromatous / Q000097:blood / Q000175:diagnosis*; D009961:Orosomucoid / Q000032:analysis*; D020543:Proteome
chemical_list: D015415:Biomarkers; D009961:Orosomucoid; D020543:Proteome