Mikroribonukleinsäuren (miRNA) als Biomarker für juvenile idiopathische Arthritis-assoziierte Uveitis (JIAU)

Grunddaten zu diesem Projekt

Beschreibung

Uveitis is a vision-threatening disease occurring in children and adults. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, and 1 in 10 patients in Germany will develop an associated severe sight-threatening anterior uveitis (JIAU) within their first four years of JIA onset. JIAU patients are typically HLA-B27 negative, antinuclear antibodies (ANA) positive, and uveitis is characterized by insidious onset, chronic course, and common development of vision threatening complications. Treatment and prognosis are hampered by not well-defined pathogenesis, probably involving both innate and adaptive immune responses. Biomarkers for disease occurrence, severity and course of JIAU will ease an appropriate uveitis management and prediction. The aim of the study is to identify a panel of circulating micro ribonucleic acids (miRNAs) with biomarker potential for uveitis associated with JIA. Firstly, expression levels of serum miRNAs in JIA patients with active or inactive uveitis shall be profiled by small RNA sequencing and compared. Subsequent comparison of the differentially expressed miRNAs with miRNA profiles in JIA patients without uveitis shall define the candidate miRNAs specific for active JIAU. Disease-relevant provenance of these candidate miRNAs shall then be validated by RT-qPCR in iris and aqueous humor (AqH) samples from JIAU patients, where also insight into potential molecular mechanisms of validated miRNAs shall be obtained through correlation with transcriptomics data generated by RNA sequencing (RNA-seq). The properties of validated serum miRNAs as biomarkers for JIAU (sensitivity and specificity) shall be assessed through machine learning algorithms using JIA-unrelated control groups. The results may further point out whether miRNAs will allow predicting JIAU -susceptibility, disease course, response to treatment, and may disclose pathogenic mechanisms in the JIAU analyzed.