Somatostatin, dendritic cells and peptide T in psoriasis : a clinical, immunohistochemical and functional study

Peptide T is an octapeptide designed to block the CD4 receptor. In a phase 1 study 9 psoriasis patients were treated with 2 mg peptide T i.v. once daily for 28 days and followed for a further 3 months. Five patients improved their PASI score >50%. The clinical results were confirmed by assessments of the histopathological score and epidermal thickness on biopsies. Peptide T treatment caused an increase in CD1-positive dendritic cells and a decrease in infiltrating lymphocytes. Immunohistochemical analysis revealed major changes in a population of somatostatin-immunoreactive dendritic cells during the treatment. Somatostatin is a neuropeptide that inhibits the release of several hormones. It also affects fundamental lymphocyte functions, such as proliferation and antibody production, and somatostatin has been used in several studies of psoriasis. We found more somatostatin- immunoreactive cells in psoriasis lesions than in normal skin. These cells did not co-express CD1a, CD35, CD45RB, CD45RO, CD68, factor XIIIa or S-100, and they probably represent a specific population of dendritic cells. A subgroup co-expressed HLA-DR, which suggests that these cells can present antigens to T-cells. Changes in somatostatin- and factor XIIIa-immunoreactive dendritic cells in psoriatic skin were then studied in biopsies taken during treatment with clobetasol propionate or calcipotriol. We found a significant reduction in the number of somatostatin- and factor XIIIa-positive cells after both treatments. The rate of reduction in the somatostatin-positive cells differed between the groups and closely paralleled healing. Most somatostatin-positive cells in psoriasis are found in the dermis. In view of the known effects of somatostatin on the immune system, these cells may regulate the function of surrounding lymphocytes. Somatostatin exerts its effects by binding to five distinct receptors (SSTR1-5). We used RT-PCR to map the mRNA expression of these receptors in normal blood T-lymphocytes and in eight leukemic T-cell lines. Normal T-cells, but not the leukemic T- cells, expressed mRNA for SSTR1 and SSTR 5. SSTR2, 3 and 4 were present in all the T-cells examined. SSTR5 was selectively expressed in activated normal T-cells. Normal T- lymphocytes and all the T-cell lines were negative with respect to somatostatin mRNA expression. Thus, although T-cells can respond to somatostatin, they do not seem to produce somatostatin themselves. A prerequisite for the localization of T-lymphocytes in specific tissue sites, such as the skin, is that they can adhere specifically to endothelial cells and extracellular matrix (ECM) components. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced the adhesion of T-cells to fibronectin, and to a certain extent also to collagen type IV and laminin. Thus, somatostatin regulates T-cell adhesion to ECM components via distinct receptor subtypes. Our findings indicate that somatostatin may be a major regulator of a fundamental lymphocyte function, the capacity of adhesion to ECM components. They also suggest that SSTR subtypes may be useful targets for therapy in disorders involving T-cells

Factors associated with adverse COVID-19 outcomes in patients with psoriasis : insights from a global registry–based study

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization. Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors. Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94). Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates