Massive recruitment of eosinophils into the dermis is a hallmark of bullous pemphigoid pathogenesis. Identifying the chemoattractant(s) guiding eosinophils into the skin in bullous pemphigoid is a prerequisite to therapeutic targeting of eosinophil recruitment. Galectin-9 is a potent chemoattractant for eosinophils, but its potential role in bullous pemphigoid is unknown. The aim of this study was to determine the expression levels of galectin-9 in serum and skin of patients with bullous pemphigoid. Galectin-9 levels were significantly elevated in serum of patients with bullous pemphigoid compared with age- and sex-matched controls, but did not correlate with disease activity assessed with the Bullous Pemphigoid Disease Area Index. Galectin-9 expression was also increased in lesional skin of patients with bullous pemphigoid, and was expressed predominantly in eosinophils, neutrophils and keratinocytes. In conclusion, these results support the notion that galectin-9 may play a role in the pathogenesis of bullous pemphigoid.

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Bullous pemphigoid (BP) is an autoimmune skin blistering disease afflicting mostly the elderly and is associated with significantly increased mortality. Here, we conducted the most extensive sampling effort of skin microbiota in BP to date to analyze whether intra-individual, body-site-specific, and/or geographical variation contributes to the emergence of BP. We find marked differences in the skin microbiota of BP patients compared to that of control subjects, and moreover that disease status rather than skin biogeography governs the skin microbiota composition in BP. Our data reveal a discernible transitional stage between normal and diseased skin in BP characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, S. aureus is ubiquitously associated with disease status, suggesting that this taxon is an important indicator of BP. Importantly, differences in a few key indicator taxa are able to reliably discriminate between BP patients and controls, characterized by their opposing abundance patterns. This may serve as valuable information for assessing disease risk and treatment outcomes. Future research will focus on the functional analysis of host-microbe and microbe-microbe interactions and the relevance of the host genome for microbiota abundances to identify novel BP treatment approaches.