Background/Purpose:

Approximately
25% of psoriasis (Ps) patients develop into psoriatic arthritis (PsA) within 10 years. This Ps-to-PsA
transition paradigm provides a unique opportunity to recognize preclinical symptoms
to prevent further joint destruction by early intervention. Early
identification of Ps patients prone to develop PsA,
however, has been challenging due to diverse Ps clinical features, limited
understanding of the molecular events, and the absence of reliable biomarkers.
To fill up these gaps, we focused our studies on DC-STAMP (Dendritic Cell-Specific
Transmembrane Protein), a
7-pass transmembrane protein essential for osteoclast
(OC) differentiation. We previously demonstrated an elevated frequency of DC-STAMP+
osteoclast precursors (OCP) in PsA patients,
suggesting DC-STAMP may serve as a surrogate to monitor DC-STAMP+ OCPs in human blood. To further validate DC-STAMP as a
potential biomarker in psoriatic disease diagnosis, herein, we evaluated the circulating
OCP frequency, DC-STAMP+ cell frequency, DC-STAMP expression level in healthy control (HC), Ps, and PsA patients.

Methods:

21 PsA, 36 Ps and 20 HC
were recruited for this study from the International Psoriatic
Arthritis Research Team (IPART) registry. We
set up a standard operating procedure (SOP) by collecting blood from 20 HC one week apart. DAS28/DAS44, ESR, CRP, PASI score and disease duration years were collected. The
numbers of OCP were assessed by in vitro culture, and
the frequency of circulating DC-STAMP+ cells and DC-STAMP expression level (by mean
fluorescence intensity (MFI)) were determined by
flow cytometry analysis.

Results:

The disease duration years & PASI
score for Ps and PsA were 24.1 ± 14.6 vs. 15.2 ± 7.8
and 6.5 ± 8.2 vs. 4,6 ± 2.4, respectively. The reliability and reproducibility
of our SOP for cell isolation, staining, and flow analysis were confirmed by HC
blood that were collected one week apart from the same subject. The
results of DC-STAMP+ cell frequency and DC-STAMP expression level were
summarized by 3 dot-plots shown below.

**:
significant; N.S.: not
significant; y-axis: cell events or frequency.

Conclusion:

The frequency of OCP (dotplot (a)) and DC-STAMP+ cells (dotplot
(b)) were significantly higher in PsA patients than
HC. In contrast, the expression level of DC-STAMP as represented by the MFI was
significantly higher in Ps than HC (dotplot (c)).
These data collectively suggested that the frequency of OCP & DC-STAMP+ cells are good biomarkers of PsA, whereas the DC-STAMP expression level serves better as
the Ps biomarker. Our studies also established the ranges of OCP, DC-STAMP+ cell frequency, and DC-STAMP expression
level for the cohorts of HC, Ps and PsA. Intriguingly,
a subset of Ps patients showed an elevated frequency of DC-STAMP+ cells and an
increased DC-STAMP expression level (outliers in dotplots
(b) & (c) for Ps). These Ps patients will be followed longitudinally to
determine if these markers can predict future PsA
onset.