ABSTRACT
Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P<0.001). There were significant positive correlations between lesional H-scores for STAT3 and Psoriasis Area and Severity Index scores in epidermis (r=0.63, P<0.001), and in dermis (r=0.47, P=0.04). There was a significant positive correlation between JAK1 and STAT3 expression in epidermal lesional psoriatic skin (r=0.44, P=0.03). Conclusion: JAK1 has a proinflammatory effect in psoriasis pathogenesis, which could be mediated through increasing STAT3 expression in psoriasis. JAK1 and STAT3 tissue expression could be markers of psoriasis severity. JAK1 may be used as a target for immunotherapy in psoriasis-management programs.
ABSTRACT
OBJECTIVE: To evaluate ultrasonographic subclinical inflammatory synovitis and enthesitis in psoriasis patients, without clinical arthritis or enthesitis compared with healthy controls, with a 2-year follow-up to study the associated incidence of psoriatic arthritis (PsA). METHODS: A total of 109 consecutive psoriasis vulgaris patients without clinical signs of PsA and 90 healthy controls were included from two tertiary medical centers. Subjects underwent dermatological examination, PASI score evaluation for severity of psoriasis, musculoskeletal examination using 68/66 joints count for tenderness and swollen joints. Patients were assessed for CRP, musculoskeletal ultrasound (MSUS) in the form of grayscale ultrasound (GSUS), and power Doppler ultrasound (PDUS) for eight entheses and 34 joints to detect MSUS subclinical enthesitis and synovitis. All patients were followed-up for 2 years to detect evolving PsA. RESULTS: Subclinical enthesitis and synovitis were detected in 39.5% of psoriasis patients and 10% of controls (P < 0.001). CRP was significantly higher in psoriasis patients with MSUS manifestations (P < 0.01). PDUS and GSUS subclinical synovitis and/or enthesitis were detected at least in one site in psoriatic patients more than in controls (P < 0.05). During a 2-year follow-up of patients, the annual PsA incidence was 4.3%. Psoriasis patients who developed PsA showed a higher prevalence of baseline enthesitis, higher PDUS and GSUS synovitis scores, and higher baseline CRP level than those who did not develop PsA. CONCLUSIONS: MSUS subclinical synovitis and enthesitis are quite common in psoriasis patients. The incidence of PsA in Saudi's psoriasis patients was slightly higher than worldwide reports. Subclinical enthesitis, PDUS, and GSUS synovitis could predict PsA development.
