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Abstract Number: 0343

Co-expression of DC-STAMP and CX3CR1: Biomarkers for Tissue Resident Osteoclasts in Psoriatic Arthritis

Maria de la Luz Garcia-Hernandez1, Javier Rangel-Moreno2, Ananta Paine3, Benjamin Korman3, Marc Nuzzo4, Lihi Eder5 and Christopher Ritchlin3, 1University of Rochester, Rochester, NY, 2University of Rochester Medical Center, Rochester, NY, 3Department of Medicine, University of Rochester Medical Center, Rochester, NY, 4Department of Medicine, University of Rochester Medical Center, Rochester, 5Women’s College Research Institute, University of Toronto, Toronto, ON, Canada

Meeting: ACR Convergence 2020

Keywords: Biomarkers, bone biology, Bone Resorption, Psoriatic arthritis, rheumatoid arthritis

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Session Information

Date: Friday, November 6, 2020

Session Title: Spondyloarthritis Including Psoriatic Arthritis – Diagnosis, Manifestations, & Outcomes Poster I: Psoriatic Arthritis

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Psoriatic arthritis (PsA) patients often experience joint damage mediated by osteoclasts (OC). Although PsA pathogenesis is poorly understood, the production of the cytokines IL-17, IL 23, and TNF are implicated in disease initiation and progression. TNF and IL-17 induce the expression of CX3CR1 and the CX3CR1-Fractalkine (FKN) axis promotes inflammation and bone damage in rheumatoid arthritis (RA). In addition, a tissue-resident OC that expresses CX3CR1 was identified in murine arthritis and RA synovial tissue1. Dendritic Cell-Surface Transmembrane Protein (DC-STAMP) is expressed on OC precursors (OCP). We found that DC-STAMP-/- mouse fibroblasts exposed to TNF do not secrete FKN and that DC-STAMP-/- x TNFTg arthritic mice show impaired migration of CX3CR1+ monocytes to joints. The purpose of this study is to identify whether DC-STAMP and CX3CR1 are co-expressed on OCP in the blood and synovial tissue of PsA patients.

Methods:

We collected blood from 23 psoriatic (Ps) and 10 PsA patients to measure serum IL-17 and TNF by multiplex assay. We assessed the frequency of CD14+CX3CR1+DCSTAMP+ monocytes in the blood of Ps and PsA patients and controls. We used immunofluorescence to enumerate TNF and IL-17-producing cells in biopsies of non-lesional (NL) and lesional (L) skin of Ps and PsA patients, and qPCR to calculate fold changes in TNF and IL-17 mRNA expression in skin biopsies (L, NL). We enumerated DC-STAMP+CX3CR1+ monocyte subsets in 3 synovial and 5 PsA L skin biopsies.

Results: We found low serum TNF levels (Ps, 4.6 ± 1.05 vs PsA, 13.98 ± 6.8, p=0.04), high IL-17 mRNA expression (Ps, 40-fold ± 7.6 vs PsA, 4.6-fold, p = 0.04) and an increased number of IL-17+ cells in L skin of Ps patients (Ps, 31.5 ± 3.3 vs PsA, 7.0 ± 2.6, p = 0.0001). In contrast, PsA patients had higher systemic levels of TNF, lower IL-17 mRNA expression, and poor infiltration of IL-17+ cells in L skin. Interestingly, we visualized higher numbers of TNF-expressing cells in PsA synovial tissue than skin. Flow cytometry analysis showed an increased frequency of CD45+CD14+DC-STAMP+CX3CR1+ circulating monocytes in PsA (2.3%), compared to Ps (0.6%) and controls (0.001%). Intriguingly, DC-STAMP+CX3CR1+CD14+ and DC-STAMP+CX3CR1+ CD14– monocytes were present only in synovial tissue, while a unique subset of CX3CR1–DC-STAMP+CD14+ cells was present in PsA but not psoriasis skin biopsies.

Conclusion: These findings highlight the divergence of TNF and IL-17 expression in the serum and skin of psoriasis and PsA patients. The co-expression of CX3CR1 and DC-STAMP present only in synovial cells supports the presence of a tissue-resident OC that arises from precursors in the skin and blood.

1Hasegawa T. Nat Immuno. 2019;20:1631


Disclosure: M. Garcia-Hernandez, None; J. Rangel-Moreno, None; A. Paine, None; B. Korman, None; M. Nuzzo, None; L. Eder, AbbVie, 2, 5, 8, Eli Lilly, 2, 5, Pfizer Inc, 2, 5, UCB, 2, 5, 8, Celgene, 5, Novartis, 5; C. Ritchlin, None.

To cite this abstract in AMA style:

Garcia-Hernandez M, Rangel-Moreno J, Paine A, Korman B, Nuzzo M, Eder L, Ritchlin C. Co-expression of DC-STAMP and CX3CR1: Biomarkers for Tissue Resident Osteoclasts in Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/co-expression-of-dc-stamp-and-cx3cr1-biomarkers-for-tissue-resident-osteoclasts-in-psoriatic-arthritis/. Accessed January 15, 2021.
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