Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis

Heat shock protein 90 alpha (Hsp90 alpha) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90 alpha in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90 alpha were determined in serum samples derived from patients with AD (n = 31), DH (n = 26), CD (n = 15), and healthy controls (n = 55). Although serum concentrations of Hsp90 alpha were similar between patients with DH, CD, and healthy controls, we found that serum levels of Hsp90 alpha were significantly higher (mean value of 5.08-fold; p < 0.0001) in patients with AD when compared to patients with DH. A cutoff value calculated as 2 x standard deviation above the mean concentration of Hsp90 alpha in DH patients revealed that 83.9% (26/31) of AD patients were Hsp90 alpha positive, whereas none of the DH patients (0/26) displayed such a positivity. This preliminary study suggests a distinct role for extracellular Hsp90 alpha in the pathogenesis of AD compared to DH and its potential use in distinguishing AD from DH. Nevertheless, the potential role of the evaluation of extracellular Hsp90 alpha for distinguishing between AD and DH is at present speculative and requires further and careful observations.