gms | German Medical Science

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which affects the synovium of joints and manifests clinically as a polyarthritis with typical symptoms such as pain, swelling, stiffness and limitations in joint function. RA patients exhibit increased activity of the peptidyl arginine deiminase (PAD) and consequently an enhanced citrullination of peptides. Autoantibodies, so-called ACPAs (anti-citrullinated protein antibodies), can be formed against these cyclic citrullinated peptides (CCP). Detection of ACPAs or rheumatoid factor (RF) indicates a seropositive RA, whereas seronegative RA patients are clinically conspicuous without detectable autoantibodies.

Methods: In the course of the UCA-Reg study, total RNA was isolated from 32 whole blood samples of RA patients and sequenced afterwards. The transcriptome analysis aimed to provide information on whether seronegative and seropositive RA can already be distinguished on mRNA level and to reveal if individual genes are differentially regulated in the two groups (seropositive and seronegative). Finally, bioinformatic data will be correlated with clinical parameters, subdivided into 30 categories (e.g., therapy, gender, severity of disease).

Results: First results of a principal component analysis (PCA) revealed clustering of the two patient groups. Seropositive and seronegative samples formed separate clusters. Furthermore, this finding correlated with the clinical observations.

Conclusion: Based on these first analyses, our study lead to the assumption that RA can already be distinguished on mRNA level and that seems to enable the characterization of seronegative and seropositive patients. These first findings will be validated by using a larger cohort. In addition, the role of individual genes in both clusters will be investigated more detailed in the course of differential gene expression analysis. Final objective of our study is the identification of new biomarkers for the diagnosis or prognosis of RA as well as revealing potential target genes for the development of new therapeutics and treatment strategies.