In healthy human skin host defense molecules such as antimicrobial peptides 
(AMPs) contribute to skin immune homeostasis. In patients with the congenital 
disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result 
patients have recurrent skin infections. The disease is characterized by 
developmental abnormalities of ectodermal derivatives and absent or reduced 
sweating. We hypothesized that ED patients have a reduced skin immune defense 
because of the reduced ability to sweat. Therefore, we performed a label-free 
quantitative proteome analysis of wash solution of human skin from ED patients 
or healthy individuals. A clear-cut difference between both cohorts could be 
observed in cellular processes related to immunity and host defense. In line 
with the extensive underrepresentation of proteins of the immune system, 
dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin 
secretome of ED patients. In contrast, proteins involved in metabolic/catabolic 
and biosynthetic processes were enriched in the skin secretome of ED patients. 
In summary, our proteome profiling provides insights into the actual situation 
of healthy versus diseased skin. The systematic reduction in immune system and 
defense-related proteins may contribute to the high susceptibility of ED 
patients to skin infections and altered skin colonization.