Proteomic profiling of immunoglobulin A nephropathy in serum using magnetic bead based sample fractionation and matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

I A nephropathy (IgAN) is characterized by renal mesangial deposits of IgA. It can often lead to end stage renal disease (ESRD), and there is no known treatment proven to prevent ESRD in IgAN. It requires successful early detection along with adequate treatment for IgAN classification and diagnosis. Percutaneous renal biopsy is currently the only means to make a definite diagnosis. Unfortunately, biopsies are inconvenient, invasive and painful, and can result in some complications. Proteomics is a new, exciting, and largely unexplored area in IgAN. Preliminary studies have shown that this technique may provide a novel means of diagnosing IgAN, and it may have an additional value as a prognostic tool.1 Serum proteome analysis has the potential to facilitate disease diagnosis and therapeutic monitoring, because serum is more easily accessible and widely collected compared to biopsy specimens that contains >10,000 different proteins and peptides.2 Advances in mass spectrometry (MS) now could display thousands of peptides using trace quantity of serum.3,4 The goal of this study was to obtain the serum peptide fingerprint in IgAN patients, to assess the utility of peptide profiling in a small sample population to identify potential biomarkers of IgAN, and to launch preliminary work for better understanding of the pathogenesis and early diagnosis of IgAN from an integrated perspective of proteomics. We conducted this study in the Central Laboratory of the Department of Nephrology, 181 Hospital, Guilin, Guangxi Province, China from October 2009 to March 2010, using a novel platform called ClinPro Tools.5 Thirty-three patients with biopsy confirmed IgAN (15-51 years old, 14 males, 19 females) were studied. Thirteen healthy volunteers (28-51 years old, 7 males, 6 females) served as normal controls, and 12 minimal change nephrotic syndrome (MCNS) (16-45 old, 9 males, 3 females), 10 membranous nephropathy (15-43 old, 9 males, 1 females), and 10 focal segmental glomerulosclerosis (FSGS) (22-59 years old, 8 males, 2 female) served as disease controls. This study was approved by the Ethics Committee of the institution. Data analysis was carried out using ClinPro Tools software 2.2 (Bruker Daltonik, Bremen, Germany). Statistical significance of different quantity of peptides was determined by means of Welch’s t-tests. A p-value of <0.05 was considered statistically significant. Class prediction model was set up by Genetic Algorithm (GA). In our study, we successfully demonstrated that peak amount and peak area of peptide panels by magnetic