AUTHOR=Castañeda-Delgado Julio E. , Bastián-Hernandez Yadira , Macias-Segura Noe , Santiago-Algarra David , Castillo-Ortiz Jose D. , Alemán-Navarro Ana L. , Martínez-Tejada Pedro , Enciso-Moreno Leonor , Garcia-De Lira Yolanda , Olguín-Calderón Diana , Trouw Leendert A. , Ramos-Remus Cesar , Enciso-Moreno Jose A. TITLE=Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00285 DOI=10.3389/fimmu.2017.00285 ISSN=1664-3224 ABSTRACT=Background

Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual’s life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.

Methods

Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA−), and healthy controls were recruited at “Unidad de Artritis y Rheumatismo” (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.

Results

Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05).

Conclusion

Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.