Circulating heat shock protein 90 (Hsp90) and autoantibodies to Hsp90 are increased in patients with atopic dermatitis

Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory dermatoses characterized by persistent itching and recurrent eczematous lesions. While the primary events and key drivers of AD are topics of ongoing debate, cutaneous inflammation due to inappropriate IgE (auto)antibody–related immune reactions is frequently considered. Highly conserved and immunogenic heat shock protein 90 (Hsp90), a key intra- and extracellular chaperone, can activate the immune response driving the generation of circulating anti-Hsp90 autoantibodies that are found to be elevated in several autoimmune disorders. Here, for the first time, we observed that serum levels of Hsp90 and anti-Hsp90 IgE autoantibodies are significantly elevated (p < 0.0001) in AD patients (n = 29) when compared to age- and gender-matched healthy controls (n = 70). We revealed a positive correlation (0.378, p = 0.042) between serum levels of Hsp90 and the severity of AD assessed by Scoring Atopic Dermatitis (SCORAD). In addition, seropositivity for anti-Hsp90 IgE has been found in 48.27% of AD patients and in 2.85% of healthy controls. Although further studies on a larger group of patients are needed to confirm presented data, our results suggest that extracellular Hsp90 and autoantibodies to Hsp90 deserve attention in the study of the mechanisms that promote the development and/or maintenance of atopic dermatitis.

Matrine regulates Th1/Th2 inflammatory responses by inhibiting the Hsp90/NF‐κB signaling axis to alleviate atopic dermatitis

“…As previously reported, serum Hsp90 level notably increased in AD patients. 15 Herein, the Hsp90 protein level was markedly elevated in the ear skins of AD mice, and this change was abolished by matrine treatment (Figure 2A). As reported, Th2 skewing is the key point in the pathogenesis of AD.…”

“…13 Hsp90 was significantly upregulated in the serum of AD patients, and its level was positively correlated with the severity of AD. 15 More importantly, matrine can serve as an Hsp90 inhibitor for cancer therapy. 30 However, whether matrine achieves its biological function in AD by targeting Hsp90 remains unknown.…”

“…In addition, Debio 0932 (Hsp90 inhibitor) administration can effectively relieve disease symptoms in a xenograft model of psoriasis 14 . More importantly, the severity of the disease in AD patients is positively correlated with serum Hsp90 levels 15 . Nevertheless, the role of Hsp90 in AD has not been fully elucidated.…”

“…14 More importantly, the severity of the disease in AD patients is positively correlated with serum Hsp90 levels. 15 Nevertheless, the role of Hsp90 in AD has not been fully elucidated. Moreover, whether matrine acts on Hsp90 and regulates its downstream targets, which ultimately affects the Th1/Th2 inflammatory response in AD, remains unclear.…”

Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases

“…In the same study, anti-Hsp90 IgE serum positivity was characterized for about 50% of AD patients and less than 3% of healthy controls. These results suggest a possible role of the extracellular Hsp90 and anti-Hsp90 IgE autoantibodies in the development of AD, as well as providing potential novel disease biomarkers [ 112 ].…”