Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. It is known that treatment modalities are not equally effective for both skin and joint disease, indicating that there are different pathomechanisms driving each component.  For example, TNF antagonists are relatively effective treatments for both psoriasis vulgaris and skin/joint manifestations of PsA. However, results from the set of emerging IL-17 antagonists for psoriasis show marked psoriatic lesional skin improvement, but less robust results for PsA joint symptoms. The purpose of this study was to determine differential gene expression between matched lesional skin and affected synovial tissue in patients with psoriatic arthritis to better define the inflammatory pathways of PsA in both skin and joint pathogenesis.

Methods: Matched lesional psoriatic skin samples and synovial samples from inflamed joints were obtained from subjects with PsA (n=13).  Gene expression analysis was conducted using Affymetrix HGU133 2.0 plus arrays.  The gene expression profile of each diseased tissue was then compared to that of corresponding normal tissue.  We considered differentially expressed genes (DEGs) with a cut-off of fold change >2.0 and false discovery rate <0.01.  Results were confirmed using RT-PCR with coupled directed pre-amplification.  Ingenuity Pathway Analysis (IPA) was utilized to identify canonical pathways among differentially expressed genes. 

Results:  Principal components analysis demonstrates that there is a clear difference between gene expression patterns of skin and synovium from psoriatic arthritis patients even when adjusted for tissue specificity.   The total number of DEGs after adjustment for tissue specificity in both skin and synovium was 2532.  The number of genes shared by both was 518.  The number of genes unique to the skin was 686 and to synovium was 1328. IPA revealed that the role of IL17A in psoriasis was significant in lesional skin but not in synovial tissue.  RT-PCR confirmed the marked expression of IL17A, IL17F, and IL22 in lesional skin compared to inflamed synovium (p<0.05). TNF was present in both tissues without any significant difference between the two. There was no correlation at the messenger level of IL17A, IL17F, IL22 and TNF between pairs of skin and synovium from the same subject.

Conclusion: These results demonstrate that gene expression differs greatly between matched pairs of lesional psoriatic skin and synovium from inflamed joints in patients with PsA.  Our results support clinical trial data that indicate psoriatic arthritis skin and joint disease are both responsive to TNF antagonists whereas skin shows better results when compared to joints with IL17 antagonists.  Genes selectively expressed in PsA synovium might direct future therapies for this condition.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-17-expression-is-low-in-psoriatic-arthritis-synovium-compared-to-expression-in-matched-skin-lesions/