C Skoglund1, A L Carlsen2, M Weiner3, T Kurz1, Thomas Hellmark4, P Eriksson5, N H H Heegaard6, M Segelmark3. 1. Department of Medical and Health Sciences, Linköping University, Sweden. 2. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark. 3. Department of Medical and Health Sciences, and Department of Nephrology, Linköping University, Sweden. 4. Department of Clinical Sciences, Lund University, Sweden. 5. Department of Clinical and Experimental Medicine, and Department of Rheumatology, Linköping University, Sweden. 6. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, and Department of Clinical Biochemistry and Pharmacology, University of Southern Denmark, Odense, Denmark.
Abstract
OBJECTIVES: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV. METHODS: Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data. RESULTS: Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels. CONCLUSIONS: In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.
OBJECTIVES: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV. METHODS: Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data. RESULTS: Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels. CONCLUSIONS: In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.
Authors: Peter Lamprecht; Anja Kerstein; Sebastian Klapa; Susanne Schinke; Christian M Karsten; Xinhua Yu; Marc Ehlers; Jörg T Epplen; Konstanze Holl-Ulrich; Thorsten Wiech; Kathrin Kalies; Tanja Lange; Martin Laudien; Tamas Laskay; Timo Gemoll; Udo Schumacher; Sebastian Ullrich; Hauke Busch; Saleh Ibrahim; Nicole Fischer; Katrin Hasselbacher; Ralph Pries; Frank Petersen; Gesche Weppner; Rudolf Manz; Jens Y Humrich; Relana Nieberding; Gabriela Riemekasten; Antje Müller Journal: Front Immunol Date: 2018-04-09 Impact factor: 7.561