Michela Ortoncelli

Circulating CD4+CD25 bright FOXP3+ T cells are up-regulated by biological therapies and correlate with the clinical response in psoriasis patients.

Background: Regulatory T-cell (Treg) modulation is one of the potential mechanisms of anti-tumour-necrosis-factor biological agents. However, literature data on psoriasis patients are lacking. Objective: To analyse the circulating CD4+CD25brightFOXP3+ subset in 30 patients with psoriasis vulgaris/arthropathic psoriasis treated with biologicals and to investigate its relationship with the clinical response. Methods: The CD25brightFOXP3+ expression within the CD4+ subset was determined by multi-parameter flow cytometry at baseline and during treatment. FOXP3 mRNA expression was analysed by real-time reverse transcription PCR. Results: A response was obtained in 16/17 patients (91.1%) with increased CD25brightFOXP3+ values and in only 3/11 patients (27.3%) who showed a CD25brightFOXP3+ decrease during biological treatment (p = 0.0001). Responders showed significantly higher values than did non-responders as from the first 2 months of treatment (p = 0.0032). A significantly higher posttreatment expression of mRNA FOXP3 was observed in responders compared to non-responders. Conclusion: Biological drugs induce a circulating Treg up-regulation in a significant percentage of patients; such an increase is an early predictive marker of response.

Expression Pattern of Chemokine Receptors and Chemokine Release in Inflammatory Erythroderma and Sézary Syndrome

Background: Erythroderma can be caused by inflammatory dermatoses or cutaneous T-cell lymphoma. Even if chemokines and their receptors are involved in the skin-selective lymphocyte recruitment, their role in inflammatory erythroderma is yet unclear. Objective: To evaluate the chemokine release (TARC, MDC, IP-10) and to define the expression pattern of Th1- (CCR5, CXCR3) and Th2-related (CCR4) chemokine receptors in inflammatory erythroderma and Sézary syndrome (SS). Materials and Methods: Flow cytometry has been carried out on both circulating and skin-infiltrating T lymphocytes; serum chemokine levels have been evaluated using ELISA techniques. Results: CCR4, CCR5 and CXCR3 were expressed on about 40% of peripheral blood lymphocytes and on the majority of skin-infiltrating lymphocytes in the inflammatory erythroderma patients, whereas the leukemic CD4+CD26– subpopulation in SS was characterized by a high CCR4 expression without a concurrent increase in CCR5 or CXCR3. TARC, MDC and IP-10 serum levels were significantly increased in both erythrodermic and SS patients. Conclusions: Our results confirm that SS is a Th2 disorder with a selective expression of CCR4, whereas inflammatory erythroderma shares an overexpression of both Th1- and Th2-related chemokine receptors, suggesting an activation of different pathways driving reactive lymphocytes to the skin.

Heterogeneity of Circulating CD4+ Memory T-Cell Subsets in Erythrodermic Patients: CD27 Analysis Can Help to Distinguish Cutaneous T-Cell Lymphomas from Inflammatory Erythroderma

Background: Chronic dermatoses, as well as Sézary syndrome (SS), the erythrodermic and leukaemic cutaneous T-cell lymphoma, display a T-cell memory pattern. Recent findings suggest that different memory T-cell subsets can be recognized based on CD27 and CD45RO/RA expression. No data are reported as to CD27 expression in SS. Objectives: To evaluate different memory T-cell subsets, i.e. central memory (TCM), effector memory (TEM) and terminally differentiated cells in SS and inflammatory erythroderma (IE). Materials and Methods: Forty SS and 137 IE patients were included. CD27 and CD45RO/CD45RA expression was analysed by flow cytometry on peripheral blood lymphocytes and immunohistochemistry.Results: A significantly higher expression of the CD4+CD27+CD45RA– TCM subset was observed in SS whilst IE patients were characterized by increased CD4+CD27–CD45RA– TEM levels. The Vβ-restricted population was homogeneously CD4+CD26–CD27+ in the SS subjects. Conclusions: SS and IE are characterized by a different memory T-cell subset expression; CD27 expression could be used as an additional diagnostic tool in the differential diagnosis.

Adult-onset cutaneous mastocytosis in monozygotic twins

(mean age 42 years). In our presentation of monozygotic twins, genetic influences were identical and the environmental influences were very similar, except for the intake of hydroxyurea for essential thrombocytosis by the twinwith squamous dysplasia. The patient presented is case-controlled by her monozygotic twin, with the one important difference between them being the long-term use of hydroxyurea. This therefore provides further evidence for hydroxyurea causing cutaneous squamous dysplasia.