Brief Report: Expression of Interferon‐γ Receptor Genes in Peripheral Blood Mononuclear Cells Is Associated With Rheumatoid Arthritis and Its Radiographic Severity in African Americans

Abstract

BACKGROUND Factors responsible for radiographic severity of rheumatoid arthritis (RA) in African-Americans are poorly understood. We sought to identify genes whose expression in peripheral blood mononuclear cells (PBMCs) is associated with radiographic severity of RA. METHODS We initially performed quantitative real-time (qRT)-PCR for 182 genes based on plausible immune pathways in 40 African-American RA patients with extremes of radiographic damage (low versus high radiographic scores) and disease duration (early versus late) and 20 healthy African-American controls. In the second phase, we analyzed the expression of significantly associated candidate genes (IFNGR2 and its biological partner IFNGR1) with radiographic scores in 576 African-American RA patients and 51 controls not previously analyzed, accounting for autoantibody status and disease duration. RESULTS We found significant differences in IFNGR1 expression between RA and controls (P=6 × 10−14) and in IFNGR2 expression between those with erosions vs no erosions (P=0.01) (Wilcoxon sum test). We also found A significant correlations between IFNGR2 expression and radiographic scores (P=0.03 for erosions, P=0.04 for joint space narrowing, and P=0.03 for total radiographic score, zero-inflated negative binomial model) and annualized progression rate (P=0.0024, Spearman correlation). CONCLUSIONS These findings have important implications with respect to IFNγ for the pathogenesis of RA and may lead to identification of a biomarker for radiographic damage. Additional studies are needed to define cell subsets responsible for the association of IFNγ receptor gene expression with radiographic finding, which downstream mechanisms are involved, and generalizability to other RA populations.

Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23

“…This cytokine plays an important role in autoimmunity, since it is involved in macrophage activation, enhanced MHC expression on neighbouring cells, balancing Th1/Th2 cell differentiation, and inducing the secretion of other pro-inflammatory cytokines [66]. Although it has been shown that an increased expression of IFNGR1 in blood is associated with RA [67], we did not detect an effect of rs6927172 genotype on this gene’s expression levels in CD4+ and CD8+ T cells. eQTLs, though, are context-specific [6, 68–72] and, therefore, it would be interesting to explore whether the SNP influences IFNGR1 expression in other cell types and/or under different stimulatory conditions.…”

Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

“…Elevated expression of ACVR1B was reported in serous ovarian cancer (Dean et al 2017). The increased transcriptional expression of IFNGR1 was documented in several infection cases (Tang et al 2015;Dettleff et al 2017). The observed up-regulation of all these transcripts may be the result of host-pathogen D r a f t interactions in the sick pigs, however, further investigation is needed to help understand the dynamic regulation network.…”

Genetic influences on susceptibility to rheumatoid arthritis in African-Americans

“…Because EBNA3C accentuates the effects of E2F6 and ZBTB7A, it seems possible that the C allele of rs9974603 and the T allele of rs9975155 serve to increase binding of these transcription factors to the IFNGR2 promoter, thereby increasing IFNGR2 expression in RA. We have recently shown that increased expression of IFNGR2 in peripheral blood mononuclear cells (PBMCs) is strongly associated with radiographic severity of RA in our Consortium for Longitudinal Evaluation of Early Arthritis Registry (CLEAR) AA cohort (72). Prior evidence suggests that increased expression of IFNGR2 in RA is most likely to occur in T cells (73), B cells or macrophages (74).…”