Chronic idiopathic urticaria: infiltrating cells and related cytokines in autologous serum-induced wheals

The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in subjects who present a whealing response to the intradermal injection of autologous serum,suggesting the presence of pathogenic antibody activities. In this study,we examined 28 chronic urticaria subjects with positive autologous serum skin test (ASST),all of whom presented autologous serum-induced lesions at different evolutive stages. Punch biopsies were taken from lesional skin of six subjects at 10V,eight subjects at 30V,six subjects at 60V,and four subjects each at 24 and 48 h. Immunological studies focussed on infiltrating cell immunophenotype and related cytokines,chemokines and chemokine receptors,adhesion molecules. Immunohistochemical staining was performed to measure expression of CD3,CD4,CD8,tryptase,eosinophil cationic protein,myeloperoxidase,basophil granular protein,IL-4,IL-5,IL-8,CCR3 and CXCR3,ICAM-1,VCAM and ELAM. Control staining was done on unaffected skin from the patients and normal skin from four healthy donors. The main infiltrating population was represented by neutrophils,seen focally in both unaffected skin (P = 0.001) and healthy controls (P = 0.003). IFN-g and IL-5 were expressed focally in autologous wheals. Significant staining for IL-4 was seen at 30V. CCR3 and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P < 0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest expression at 30V and 60V in induced lesions,and they showed strong expression also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the immunoinflammatory features of ASST-induced wheals involve a prevalent role of lymphocytes (with a mixed Th1/Th2 response),with strong neutrophil infiltration and activity and involvement of the chemokine pathway. We interpreted the finding of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign of prolonged and widespread "urticarial status".