Background/Purpose: Psoriatic arthritis is an inflammatory musculoskeletal disease which develops in 30% of patients with psoriasis. Our previous peripheral blood microarray study identified CXCL10, NOTCH2NL, HAT1, and SETD2 as differentially expressed between PsA and psoriasis patients without arthritis (PsC). This study aimed to determine gene expression in leukocyte subsets to elucidate their functions in psoriatic disease.

Methods: Peripheral blood mononuclear cells were isolated using Ficoll paque separation from PsA and PsC patients not receiving biologic therapy and healthy controls (HC). T cells (CD3+), monocytes (CD14+), and NK cells (CD56+) were separated by positive selection. mRNA was extracted using RNeasy miniprep kits and qPCR performed with 75ng mRNA to determine CXCL10, CXCR3, NOTCH2NL, IL-17A, HAT1, and SETD2 gene expression. A two-way ANOVA with Bonferroni’s post-hoc test was used to determine significant differences (p<0.05).

Results: Gene expression was measured in 15 PsA (mean age 59, 60% males), 15 PsC (mean age 57, 67% males), and HC (mean age 54, 60% males). Expression of IL-17A in monocytes was 18.42-fold greater in PsA patients than PsC (p<0.0001) and 31.36-fold greater in PsA than HCs (p<0.0001). There were no other significant differences in gene expression between disease groups in each given cell type. However, in T cells, CXCL10 was elevated in PsA compared to PsC (1.42-fold) and HC (2.47-fold). A similar trend was found for the receptor, CXCR3, where expression was higher in PsA than PsC (1.18-fold) and HC (1.13-fold). Finally, SETD2 expression in PsA was higher than PsC (1.65-fold) and HC (1.28-fold) in T cells. CXCL10 expression in monocytes (p<0.0001; 11.1-fold) and NK cells (p<0.0001; 2.04-fold) was higher than in T cells. Expression of CXCR3 was higher in T cells compared to monocytes (p<0.0001; 208.17-fold) and NK cells (p<0.0001; 1.3-fold). HAT1 was more highly expressed in T cells as compared to monocytes (p=0.0003; 3.41-fold) and NK cells (p=0.0274; 1.48-fold). Expression of SETD2 was elevated in T cells compared to monocytes (p=0.0007; 3.2-fold) and NK cells (p=0.0082; 1.22-fold). NOTCH2NL expression was elevated in T cells compared to monocytes (p=0.0154; 2.43-fold).

Conclusion: Genes of interest were differentially expressed in leukocyte subsets. The higher expression of these genes in PsA compared to PsC and HCs could provide insight into their role in driving the development of PsA. Knowing which cell types are predominantly involved with expression of certain biomarkers will aid in developing targeted treatments.