Autoimmunity (or Not) in Atopic Dermatitis

Abstract

Atopic dermatitis (AD), one of the most frequent inflammatory skin diseases worldwide, is believed to result from a disturbed skin barrier as well as aberrant immune reactions against per se harmless allergens. Starting mostly during childhood with a chronic, remitting relapsing course, the disease can persist into adulthood in about one fifth of patients. Immune reactions to self-proteins have been observed in AD patients already in the beginning of the Twentieth century, when human cellular extracts were shown to provoke skin lesions. However, the term “autoimmunity” has never been claimed, since AD is first and foremost an atopic disease. In contrast, this IgE-hallmarked autoreactivity was termed “autoallergy” and is ongoing discussed regarding its impact on the disease. Since severely affected patients tend to develop IgE-hypersensitivity reactions to numerous environmental allergens, the impact of immune responses to self-proteins is difficult to determine. On the other hand: any autoreactivity, irrespective of the magnitude, implicates the potential of driving the chronification of the disease while shaping the immune response. This review article revisits the observations made on autoallergy from an actual point of view and tries to approach the question whether these still point to a contribution to the disease.

IgE autoantibodies and autoreactive T cells and their role in children and adults with atopic dermatitis

“…In more recent years, a wide range of autoantigens have been described. The most relevant targets are summarized in Table 2 and were previously listed by others [ 21 , 22 , 56 ]. Patients with the highest total serum IgE values, showed the highest frequency of anti-keratinocyte IgE [ 33 ].…”

“…Evolutionary well conserved peptides in humans can share similar protein structures with pathogens which may lead to molecular mimicry after exposure to the pathogens. Serum IgE from subjects sensitized to thioredoxins (Trx) of Malassezia sympodialis (Mala s 13), Malassezia furfur or Aspergillus fumigatus were shown to cross-react with human Trx proteins leading to immediate allergic responses [ 22 , 33 , 66 ]. Likewise, the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of fungal origin can also induce a humoral response against human MnSOD based on molecular mimicry.…”

Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin

“…The relevance for these autoantibodies as primary causes of the disease versus epiphenomenon is unclear. 45…”

IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

“…At least 13 allergens from this yeast have been described, but several Malassezia specific IgE and T cells show a strong crossreactivity to identified autoantigens. Thus, it is not currently known if the Malassezia sensitization seen in AD arises from autoimmunity or if the sensitization to these commensals leads to the emergence of autoreactive T cells and IgE [ 27 , 28 ].…”

“…Th22, Tc22, and Th1 cells also expand to variable degrees during the AD pathogenesis, especially in the adult chronic presentation. These T cells are thought to react more to autoantigens than Th2 cells [ 28 , 40 ]. Experimental atopic skin inflammation induces the emergence of CD4+ T cells producing IL-4, IL-13, or both, which shows an effector ( bona fide Th2 cells) or a follicular (Tfh2 cells) phenotype [ 41 ].…”