Different expression of fibrinopeptide A and related fragments in serum of type 1 diabetic patients with nephropathy.
Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease affecting about 0.12% of the world's population. Diabetic nephropathy (DN) is a major long-term complication of both types of diabetes and retains a high human, social and economic cost. Thus, the identification of markers for the early detection of DN represents a relevant target of diabetic research. The present work is a pilot study focused on proteomic analysis of serum of controls (n=9), IDDM patients (n=10) and DN patients (n=4) by the ClinProt profiling technology based on mass spectrometry. This approach allowed to identify a pattern of peptides able to differentiate the studied populations with sensitivity and specificity close to 100%. Variance of the results allowed to estimate the sample size needed to keep the expected False Discovery Rate low. Moreover, three peptides differentially expressed in the serum of patients as compared to controls were identified by LC-ESI MS/MS as the whole fibrinopeptide A peptide and two of its fragments, respectively. The two fragments were under-expressed in diabetic patients, while Fibrinopeptide A was over-expressed, suggesting that anomalous turnover of Fibrinopeptide A could be involved in the pathogenesis of DN.
Gianazza
E
E
Department of Experimental Medicine, University of Milano-Bicocca, via Cadore 48, 20052 Monza, Italy.
Mainini
V
V
Castoldi
G
G
Chinello
C
C
Zerbini
G
G
Bianchi
C
C
Galbusera
C
C
Stella
A
A
Mauri
G
G
Zoppis
I
I
Magni
F
F
Kienle
M Galli
MG
D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005344:Fibrinopeptide A / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D010865:Pilot Projects; D020543:Proteome / Q000032:analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D010446:Peptide Fragments; D020543:Proteome; D005344:Fibrinopeptide A