الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 103 |  |  |
| | | from | 103 | | |
Abstract
Psoriatic arthritis (PsA) is a chronic, heterogeneous disorder that is characterized by a systemic immune-mediated inflammatory arthritis, which is associated with symptoms including arthritis, psoriatic skin, enthesitis, dactylitis, spondylitis, and nail diseases.
The pathogenic process of PsA is suspected to be mediated by T-cells that make up the majority of the immune cell infiltrate in synovial tissue and involve certain proinflammatory cytokines that may affect synoviocyte invasion. There is an imbalance between Th1, Th17, and Tregs, and coinhibitory receptors are needed to control T cell activity in order to avoid host tissue damage and return to homeostasis.
PD-1 is a 55-kDa transmembrane protein, a member of the CD28 family that is expressed on CD4+T cells. Upon binding with its ligand, PD-L1 (which is expressed on activated CD4+ T cells), it blocks positive signal transmission via the TCR and CD28 by interacting via transmitting an inhibitory signal, which suppresses the activation and proliferation of these PD-1-expressing cell. Upregulation of PD-1 and PD-L1 depends on inflammatory cytokines such as IL-21.
In this study, the main aim was to detect the role of PD-1+CD4+ T cell, PD-L1+CD4+ T cells, and IL-21 in PsA patients in comparison to control group using flow cytometry to detect these cells in the peripheral blood of the subjects; and ELISA technique to detect the level of serum IL-21. We also intended to correlate both PD-1 and PD-L1 expression on CD4+ T cells and circulating IL-21 levels with disease activity index (DAPSA).
The present study included 35 subjects; twenty of them were PsA patients fulfilling CASPAR classification criteria for the disease. The other 15 were healthy controls.
Our results showed a statistical significant increase in PD-1+ CD4+ T cells and PD-L1+ CD4+ T cells in patients group compared to control group (p=<0.001*). Also, the results show no significant correlation between both frequencies of PD-1+ and PD-L1+ T cell and disease activity scores (DAPSA), neither they were significantly different between severity subgroups.
The present study results showed a highly statistically significant increase in serum IL-21 levels in the patients‘ group compared to the control group (p=0.030*). IL-21 was significantly correlated with PD-L1+CD4+T cells (p = 0.001*) and also to DAPSA. It also increases significantly in severe PsA, with significant difference between severity subgroups.
from our study results we can conclude that PsA patients have increased frequencies of CD4+ cells expressing PD-1 or PD-L1 molecules, which could result from the continuous cellular activation in chronic inflammatory conditions. We can also conclude a direct relationship between IL-21 and PD-L1+CD4+T cells that needs further exploration. Results also suggest a significant role for IL-21 in disease pathogenesis and progression as suggested by its correlation to disease activity scores and the higher levels in severe PsA patients. IL-21 could be a promising therapeutic target to reduce PsA activity.