Mg Bernengo

The relevance of the CD4+ CD26- subset in the identification of circulating Sézary cells.

Background  The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl‐aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC).

Prognostic factors in Sézary syndrome: A multivariate analysis of clinical, haematological and immunological features

BACKGROUND Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis. PATIENTS AND METHODS A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. RESULTS The median survival time was 31 months (range: 1 month-15.7+ years), and the five-year survival rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sézary cells (SC) (P < 0.001) and CD4+ cells (P < 0.001), presence of large circulating SC (P < 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P < 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P < 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045). CONCLUSIONS Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index < or = 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic feature (risk index > 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).

Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea

Background  Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases.

Multiple primary melanomas: analysis of 49 cases.

Development of multiple primary melanomas is a rare but well recognized disease, with an estimated incidence ranging from 1.75%to8.5% in several series. The clinical, histological and epidemiological characteristics of 49 patients, identified from 2470 with histologically confirmed melanoma, are described in this study. Thirty-five of these patients had two primary melanomas, 11 had three melanomas and three had four, five and six melanomas, respectively. Diagnosis was concurrent in 22 patients (45%);in the remaining cases the median time interval between the first and second melanoma was 22.6 months and the longest interval was 21.5 years.The mean Breslows thickness decreased significantly(P< 0.001) from the first melanoma to the second and third lesion. The multiple melanoma patients had a higher percentage of subjects over 70 years of age or with lentigo maligna melanoma than single melanoma patients. The mean follow-up time was 12 years (range 4-23 years). The 5-year survival rate from first melanoma excision (83%) does not differ from that of patients with a single melanoma. In conclusion, the presence of multiple primary melanomas does not appear to be a negative prognostic factor; our data show the importance of close follow-up in melanoma patients in order to detect not only metastases, but also subsequent primaries in their earliest phases.

Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients.

The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy (SLNB) in melanoma < 1 mm.

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.

Skin lesions in angioimmunoblastic lymphadenopathy: histological and immunological studies.

Angioimmunoblastic lymphadenopathy with dysproteinaemia is reported (AILD) in four patients with different skin pictures. As the disease progresses two main forms predominate: papulonodular and erythroderma. In all cases the histological picture of the skin mirrors that of the lymph‐node.

Soluble interleukin-2 receptor in Sézary syndrome: its origin and clinical application

Soluble interIeukin‐2 receptor (sIL‐2R) serum levels were evaluated in Sézary syndrome (SS). mycosis fungoides. non‐epidermotropic T‐cell lymphomas. inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow‐up of 17 SS patients showed that serum SIL‐2R correlated with the clinical course of the disease and with other haematologicai parameters (ahsolute numher of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematoiogical disorders, highly enriched resting Sézary cells were unahle to release sII‐2R. and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastie sIL‐2R source. To further support this hypothesis, the highest sIT.‐2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.

Clinical and prognostic reports from 270 patients with multiple primary melanomas: a 34-year single-institution study.

Background  Development of more than one primary melanoma in a sole patient is frequent, accounting for 1.2–8.2% of melanoma patients in most recent series.

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.