Background/Purpose: CD146, also called melanoma cell
adhesion molecule (MCAM), is a cell surface adhesion molecule.  A small
minority of the T cell population also express MCAM. The ligand for MCAM is
laminin 411. T cells expressing MCAM, are mainly responsible for IL17
production ex vivo.  Furthermore, MCAM enriches for cells secreting IL-22
and IFN-γ.  Thus, T cells expressing MCAM are uniquely capable of
producing multiple cytokines responsible for psoriatic pathogenesis. Currently,
CD4+ T cells with the capacity to secrete IL-17 (Th17 cells) have been viewed
as a primary driver for psoriatic arthritis (PsA) and psoriasis; there are role
for Th1 (IFN-γ) and Th22 (IL-22) T cells also. Thus it is likely that
these pathologic CD4+T cells of psoriatic disease need to express CD146 for
migration and localization at the disease site.  Circulating CD146+ T cells
have been reported to be elevated in several inflammatory diseases including in
psoriasis; whether these cells play a role at the disease site of active
inflammation in psoriatic arthritis remains unknown. We hypothesized that, in PsA, the synovial fluid
and synovial tissue will be enriched with CD3+CD146+ T cells.  

Methods: We studied synovial fluid mononuclear cells (SFMC), synovial
tissues and psoriasis plaques from PsA (n=10) patients and have used osteoarthritis
(OA) patients (n=10) as controls. Hi-D FACS studies were done to identify
CD4+CD146+ and CD8+CD146+ T cells in the synovial fluid and PBMC of PsA patients. Double
labeled IF study was done in synovial tissues from PsA patients and psoriasis
plaques to identify CD3+CD146+
T cells.  

Results: PsA patients showed significantly more
CD4+CD146+ T cells in PBMC compared to OA (8 ± 2.8% vs 3.96 ± 0.6%
respectively, p <0.01).  Also SF of PsA had a significant higher level of
CD4+CD146+ T cells (18 ± 3.1%; p <0.01) compared to PBMC. CD8+CD146+ T cells
in PBMC and SFMC of PsA patients were <1%; CD146+ T cells were not
identifiable in the SF of OA. CD146+ T cells were abundant within the psoriasis
plaques and PsA synovial tissues and rare in non-lesional psoriatic skin.

Conclusion: 1. Here we observed that CD4+CD146+
T cells are enriched at the site of synovial inflammation in PsA (Fig 1). As CD146+
T cells are the primary source of the lesional Th-17 cytokines it is likely
enrichment of these pathologic cells are critical for the disease process of
PsA.   2. Also this opens up a new avenue for therapy of PsA and other
autoimmune diseases. Rather than targeting individual cytokines, which often
have redundant effects, targeting MCAM provides the possibility of the
inhibiting the pathogenic cell itself, regardless of whether that cell is Th1,
Th22 or Th17.