Expression and role of integrin receptors in Sézary syndrome

The potential role of integrins in the epidermotropism of the atypical lymphocytes of Sézary syndrome was studied by monitoring the expression of α and β chains and their major ligands in skin biopsies and peripheral blood cells in patients at different progression stages. Most mononuclear cell integrins were also detected on infiltrating cells including the leukocyte complex CD 11/CD18, α4β1, and their ligands, ICAM-1 and VCAM-1. Conversely, α6 and β4 were present only in epidermal basal cells. Mononuclear infiltrates of SS were positive for both α3 and α5 chains, whereas in inflammatory cutaneous diseases only α5 was expressed, indicating that a major feature of Sézary cells is the unique expression of α3β1. Significant changes of α3β1 were monitored in the follow-up of Sézary patients and correlated with the results of the therapy. The heterodimer α1β1 was absent from mononuclear cells except in one case. Among matrix molecules, laminin and type IV collagen displayed a pattern similar to that of the controls, whereas fibronectin and tenascin deposition were apparently increased. Circulating Sézary cells, both at diagnosis and during follow-up, were α3 and β5 negative and failed to acquire these adhesion molecules after mitogenic stimulation. We propose that the expression of α3β1 is a distinguishing feature of skin-infiltrating Sézary cells and may be related to their epidermotropism. It could also be adopted as an additional parameter of the progression and therapeutic stage of Sézary syndrome.