Background/Purpose:
Psoriatic arthritis (PsA) is a destructive inflammatory arthritis that develops
in approximately 30% of patients with cutaneous psoriasis. Th17 cells
infiltrate psoriatic skin and joints and are central to the pathogenesis of
PsA. The aim of this study was to identify Th17 cell signaling genes that are
dysregulated in the affected joint of PsA patients and if these differences are
detected in peripheral blood.

Methods: Synovial
fluid cells from 8 PsA and 4 gout patients undergoing routine joint aspirations
were obtained and stored in TRIzol reagent. RNA was isolated by phenol-chloroform
extraction and purified with RNeasy miniprep kits. Peripheral blood from 24 PsA
and 19 controls was stored in Tempus tubes and total RNA was extracted
according to the manufacturer’s instructions. Quantitative RT-PCR arrays were used
to profile expression of 84 genes related to the Th17 regulatory network in synovial
and peripheral blood cells. Expression was quantified by the ΔΔCt
method and fold change differences were compared in synovial cells by logistic
regression and in peripheral blood by Student’s t test (p<0.05).

Results: Out
of 16 genes significantly dysregulated in PsA compared to gout synovial cells,
15 genes were up-regulated and one gene (STAT4) was down-regulated (Table 1). In
peripheral blood, 5 genes (IL-15, CXCL6, CLEC7A, CD3D and TLR4) were elevated
and 21 genes, including IL-8, IL-17C, CD4, STAT3, NFKB1 and TGFB1, were reduced
in PsA compared to controls. Five genes (CD4, CLEC7A, CXCL6, NFKB1 and IL8)
were significantly altered in both synovial and peripheral blood cells of PsA
patients compared to controls (gout or normal). Additionally, gene expression
was compared in paired synovial and peripheral blood cells in 4 PsA patients.
Eight genes were increased and 13 genes were reduced in PsA synovial cells
compared to peripheral blood cells (Table 2).

Conclusion: We
identified gene expression differences that may distinguish PsA from other
inflammatory arthritides such as gout. Five genes (CD4, CLEC7A, CXCL6, NFKB1
and IL8) were altered in both synovial fluid and peripheral blood, potentiating
their use as biomarkers of PsA. Differences between synovial and peripheral
blood cells contribute to our understanding of the biology of PsA and warrant
further investigation.

Table 1: Differences in
expression of Th17 signaling genes (p<0.05) in synovial cells obtained from
patients with PsA compared to that obtained from gout

*Denotes genes that were dysregulated in synovial
and peripheral blood of PsA vs. controls (gout or normal)

Table 2: Expression of
Th17 signaling genes (p<0.05) in paired synovial and peripheral blood cells
of PsA patients