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Patients with Sézary syndrome (SS) show clonal expansion in the peripheral blood of skin-homing CD4+ T-helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can also be observed in various inflammatory dermatoses. To facilitate early diagnosis and therapeutic monitoring of SS using flow cytometry, we evaluated the expression of CD7 and CD26 on the CLA+ CD4+ lymphocyte subset. Peripheral lymphocytes from 7 patients with SS, 16 patients with mycosis fungoides (MF) and 11 healthy controls were analysed by flow cytometry for the expression of CD4, CD7, CD26, CLA and CCR4. In addition, a longitudinal study was performed over 16 months in two patients with SS. Absence of CD7 and CD26 on CLA+ CD4+ T cells was highly specific for SS. Importantly, the absence of CD26 on CLA+ CD4+ T cells was very sensitive for SS, at 100% in our patient cohort. The number of CD26− CLA+ CD4+ T cells closely correlated with therapeutic interventions in the longitudinal analysis of two patients over more than 1 year. We conclude that the absence of CD26 expression on skin-homing CLA+ CD4+ T-helper cells is a very sensitive and highly specific parameter for early diagnosis and therapeutic monitoring of patients with SS. [ABSTRACT FROM AUTHOR]

Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10.To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA+ and CD4+ T cells in the peripheral blood of patients with Sézary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma.Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vβ CDR3 regions were cloned and sequenced in two patients.We found that CCR4 is expressed on almost all CLA+ and CD4+ memory T cells. Using monoclonal antibodies specific for single TCR-Vβ chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sézary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7.Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous‘central’ memory T cells in the peripheral blood of these patients. [ABSTRACT FROM AUTHOR]