Category: Autoimmune rheumatologic diseases
Psoriatic Arthitis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis. Immune factors, especially T cells, are involved in PsA. We used mass cytometry to profile proteins on circulating immune cells in active and inactive patients with Psoriatic Arthritis.
Blood from adults PsA patients with active (n=15) or inactive disease (n=13), and from patients with active Rheumatoid Arthritis (RA, n=14) was fixed with Proteomic Stabilizer (Smart Tube) and frozen at -80oC. After thawing and red cell lysis, surface and intracellular antigens were stained using metal-labeled antibodies (Fluidigm). Cells were acquired on a Helios CyTOF instrument and data analyzed using FlowJo and VisNE (Cytobank). Statistical analysis was performed using GraphPad Prism.
The frequencies of activated CD8 T cells (CD38+HLA-DR+), and classical (CD14+CD16-) monocytes were elevated in active versus inactive PsA patients. Higher frequency of T regulatory cells, defined as CD4+CD127lowCD25highFoxP3+, was found in active PsA versus active RA.
Levels of phosphorylated STAT3 (pSTAT3) was elevated in total CD4+ T cells in active PsA, and in the Th1, Th2, Th17 and Treg CD4+ T cell subsets. pSTAT3 was also elevated in CD14+CD16- monocytes from active versus inactive PsA patients.
Elevated pSTAT3 is associated with active PsA in comparison to inactive PsA in CD4+ T cells. Recent mouse studies showed that overexpression of STAT3 in CD4+ T cells was sufficient to elicit all the major characteristics of PsA, reinforcing a potential role for STAT3 signaling in the promotion of an inflammatory environment in PsA.
Claudia Macaubas– Department of Pediatrics, Human Gene Therapy at the Lucile Salter Packard Children’s Hospital, Stanford school of medicine, Stanford, CA, USA
Shamma Rahman– Department of Pediatrics, Human Gene Therapy at the Lucile Salter Packard Children’s Hospital, Stanford school of medicine, Stanford, CA, USA
Devy Zisman– Rheumatology Unit Carmel Medical Center and Ruth and Bruce Faculty of Medicine Technion Haifa, Israel
Elizabeth Mellins– Professor, Department of Pediatrics, Human Gene Therapy at the Lucile Salter Packard Children’s Hospital, Stanford school of medicine, Stanford, CA, USA