Session Type: Abstract Submissions (ACR)
Background/Purpose: Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis that develops in 30% of patients with cutaneous psoriasis (PsC). Joint inflammation in PsA is mediated in part by natural killer (NK) cells which are an important arm of the innate immune system. We have previously shown that PsA is associated with activating ligands of NK cell receptors, including the killer cell immunoglobulin-like receptors (KIRs) and NKGD2. Toll-like receptors (TLRs) and Th17 cells are components of the innate immune response which have been implicated in other inflammatory arthridities such as rheumatoid arthritis and ankylosing spondylitis. We sought to determine whether a dysregulation in these pathways is also found in PsA.
Methods: Total RNA was isolated from peripheral blood of 20 PsA, 17 PsC, and 19 control subjects. Quantitative RT-PCR arrays (SABiosciences) were used to profile expression of 155 genes related to the Th17 regulatory network and toll-like receptor signaling. Expression was quantified using the ΔΔCt method and fold change differences between groups was determined by Student’s t-test (p<0.05 cutoff).
Results: Out of 30 genes significantly dysregulated in psoriatic disease patients (PsA & PsC), two (TLR9 and IL13) were dysregulated greater than 1.5-fold (a 50% increase). 6 genes were significantly dysregulated less than 1.5-fold in PsC patients compared to controls, and one gene (IL23R) was increased 1.6-fold (p=0.049). In PsA patients compared to controls, 9 out of 45 significant genes were dysregulated greater than 1.5-fold: CLEC7A, CLEC4E, CXCL10, CXCL6, IL2, IL15, LY96, TBK1 and TLR9. Comparing PsA to PsC patients, 4 out of 50 significant genes were dysregulated greater than 1.4-fold (LY96, TBK1, CXCL10 and TLR4) and 13 of 50 significant genes were dysregulated less than 1.5-fold, including CD4, CD8A, CXCL5, NFATC2, SYK, TBX21, IRAK2 and RELA.
Conclusion: A majority of the changes observed in PsA were related to TLR signaling. LY96 dysregulation was previously identified in microarray analyses of PsA compared to PsC patients and controls. Over-expression of TLR3 and TLR4 in synovial tissue from patients with early RA has also been reported. Future studies will validate these results, examine the role of TLR signaling pathways in PsA, and determine whether they can serve as biomarkers of PsA susceptibility in patients with PsC.
D. D. Gladman,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/examining-a-role-for-th17-regulation-and-toll-like-receptor-signaling-in-psoriatic-arthritis/