Preclinical Alterations in the Serum of COL(IV)A3(-)/(-) Mice as Early Biomarkers of Alport Syndrome.
The efficiency of the inhibition of the angiotensin converting enzyme, the most widely used therapy for the Alport syndrome, depends on the onset of the therapy-the earlier the better. Hence, early progressive biomarkers are urgently required to allow for preclinical diagnosis, an early start of possible therapy as well as the monitoring of this therapy. In the present study, an improved comprehensive and precise proteomic approach has been applied to the serum of juvenile Alport-mice, nontreated and treated, and wild-type controls of various ages to search for biomarkers. With a total of 2542 stringently altered proteins, the serum composition clearly shows a dependency on age, that is, stage, and therapy. Initially, the serum constituents indicate an enhanced extracellular matrix remodeling, cell damage, and the production of particular acute phase proteins. A panel of 15 potential biomarker candidates has been identified. In later stages, renal filtration failure and systemic acute phase reaction determine the composition of the serum; an effect that is well-known for manifested human Alport syndrome. With a small number of mouse urine samples, for example, the proteomic results for gelsolin could be verified using ELISA. Once verified in man, these early biomarkers would allow for a sensitive and specific diagnosis of the Alport syndrome in children as well as facilitate the monitoring of a possible therapy.
Institute of Biochemistry I, University Hospital Jena , Nonnenplan 2-4, 07740 Jena, Germany.|Clinic of Neurology, University Hospital Jena , Erlanger Allee 101, 07740 Jena, Germany.
Petra
P
Muckova
Institute of Biochemistry I, University Hospital Jena , Nonnenplan 2-4, 07740 Jena, Germany.
Sindy
S
Wendler
Department of Nephrology and Rheumatology, University Medicine Göttingen , Robert-Koch Str. 40, 37075 Göttingen, Germany.
Diana
D
Rubel
Institute of Biochemistry I, University Hospital Jena , Nonnenplan 2-4, 07740 Jena, Germany.
Rita
R
Büchler
Institute of Biochemistry I, University Hospital Jena , Nonnenplan 2-4, 07740 Jena, Germany.
Mandy
M
Alert
Department of Nephrology and Rheumatology, University Medicine Göttingen , Robert-Koch Str. 40, 37075 Göttingen, Germany.
Oliver
O
Gross
Institute of Biochemistry I, University Hospital Jena , Nonnenplan 2-4, 07740 Jena, Germany.
Heidrun
H
Rhode
D000818:Animals; D001324:Autoantigens / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000302:isolation & purification; D002648:Child; D024141:Collagen Type IV / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D042241:Early Diagnosis; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009394:Nephritis, Hereditary / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
D001324:Autoantigens; D015415:Biomarkers; D001798:Blood Proteins; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain
noninvasive biomarkers; preclinical diagnosis; serum proteome; therapy monitoring