title: Urinary haptoglobin, alpha-1 anti-chymotrypsin and retinol binding protein identified by proteomics as potential biomarkers for lupus nephritis.
abstract: The study was aimed at identification by proteomics and validation by enzyme-linked immunosorbent assay (ELISA) of potential urinary biomarkers for lupus nephritis. Study subjects comprised 88 systemic lupus erythematosus (SLE) patients and 60 controls (rheumatoid arthritis, diabetes mellitus and healthy individuals). Based on the SLE disease activity index (SLEDAI), patients were classified as active renal (AR), active non-renal (ANR) or inactive disease (ID). Urinary proteins from a group of patients with AR or ID were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS/MS). The selected biomarkers were validated by ELISA using samples from all patients and controls. AR patients were followed-up for 12 months after start of therapy. Three urinary proteins, alpha-1 anti-chymotrypsin (ACT), haptoglobin (HAP) and retinol binding protein (RBP), were detected in patients with AR and not ID. Upon validation, ACT levels were higher in AR patients than the other groups (P < 0·001) and showed good correlation with renal SLEDAI (r = 0·577, P < 0·001) as well as SLEDAI (r = 0·461, P < 0·001). Similarly, HAP levels were > 10-fold higher in AR than other groups (P < 0·001) and correlated well with renal SLEDAI (r = 0·594, P < 0·001) and SLEDAI (r = 0·371, P < 0·01). RBP levels were also higher in AR patients than in other groups (P < 0·05), except diabetes, and showed moderate correlation with renal SLEDAI (r = 0·284, P < 0·008) and SLEDAI (r = 0·316, P < 0·003). Upon follow-up with treatment, levels of all three proteins declined at 6 and 12 months (P < 0·01). Multiple logistic regression identified ACT as the best marker to differentiate AR from ANR. Urinary HAP, ACT and RBP are potential biomarkers for lupus nephritis activity.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: A
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Clinical Immunology, JIPMER, Puducherry, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Negi
authors.affiliation: Department of Rheumatology, Nizam Institute of Medical Sciences, Hyderabad, India.
authors.forename: L
authors.initials: L
authors.lastname: Rajasekhar
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: R
authors.initials: R
authors.lastname: Misra
authors.affiliation: Biochemistry Division, Central Drug Research Institute, Lucknow, India.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: Biochemistry Division, Central Drug Research Institute, Lucknow, India.
authors.forename: V
authors.initials: V
authors.lastname: Chaturvedi
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.|Biochemistry Division, Central Drug Research Institute, Lucknow, India.
authors.forename: S
authors.initials: S
authors.lastname: Sinha
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003920:Diabetes Mellitus / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000652:urine*; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000652:urine; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine; D008297:Male; D040901:Proteomics / Q000379:methods; D012177:Retinol-Binding Proteins / Q000652:urine*; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D055815:Young Adult; D000514:alpha 1-Antichymotrypsin / Q000652:urine*
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D012177:Retinol-Binding Proteins; D000514:alpha 1-Antichymotrypsin
keywords: biomarkers; cyclophosphamide; glomerulonephritis; systemic lupus erythematosus