Background: The immunologic characterization of chronic idiopathic urticaria (CIU) is still incomplete. In particular, it is not known if positivity to the intradermal autologous serum skin test (ASST) identifies an immunologic subset of CIU patients. Methods: Nineteen CIU patients and 15 healthy controls were enrolled in the study. A diagnostic flowchart was designed to select CIU patients, who were then analyzed by ASST. Cytokine and chemokine production and the expression of adhesion molecules was measured in patients and controls. Results: In CIU patients compared to controls, it was found that (1) TNF-α, IL-10, MIP-1α and RANTES production was augmented and IL-2 and INF-γ reduced, and (2) CD44, CD11a and CD62L expression on CD4 and CD8 cells was augmented. Additionally, TNF-α and chemokine production was significantly increased in CIU patients with a negative ASST (p–; n = 10) compared to patients with a positive response to the test. Conclusions: The presence of an inflammatory process in CIU patients is suggested by the findings that the production of both TNF-α and chemokines as well as the expression of adhesion molecules is increased in these patients. Similarly to what is seen in rheumatoid arthritis, augmented IL-10 production might be secondary to the attempt to hamper the inflammatory milieu. Immune profiles are particularly altered in CIU p– patients, in whom a more aggressive therapeutic strategy might be considered.

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