Interleukin-36 cytokines are overexpressed in the skin and sera of patients with bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune bullous disease, characterized by autoantibodies targeting BP180 and BP230. The role of interleukin (IL)-36, a potent chemoattractant for granulocytes, in BP remains elusive.The expression of IL-36 cytokines (IL-36 alpha, beta, gamma) and their antagonists (IL-36Ra and IL-38) was analysed in the skin and serum samples of patients with BP (n = 31), psoriasis (n = 10) and healthy controls (HC) (n = 14) by quantitative polymerase chain reaction and enzyme linked immunosorbent assay, respectively. Skin and serum levels of all cytokines were correlated with the Bullous Pemphigoid Disease Area Index (BPDAI) score and with the serum concentration of pathogenic antibodies.IL-36 alpha, IL-36 beta, IL-36 gamma and IL-36Ra were significantly (p < 0.05) overexpressed in BP skin compared to HC, without remarkable differences relative to psoriasis skin. The expression of IL-38 was significantly (p < 0.05) higher in BP compared to psoriasis skin.IL-36 alpha and gamma, but not beta, serum concentrations were significantly (p < 0.05) higher in BP compared to HC. IL-36 gamma was significantly (p < 0.05) more expressed in the serum of psoriasis patients than BP. The serum concentration of IL-36Ra and IL-38 were similar between BP and HC, while IL-38 serum levels were significantly (p < 0.05) higher in BP compared to psoriasis patients. Serum IL-36 alpha correlated significantly with BPDAI (r = 0.5 p = 0.001).IL-36 agonists are increased in BP patients, both locally and systemically. Serum IL-36 alpha might represent a potential biomarker for BP. An inefficient balance between IL-36 agonists and antagonists is likely to occur during BP inflammation.