Atopic dermatitis and autoimmunity: the occurrence of autoantibodies and their association with disease severity

Abstract

Atopic dermatitis (AD) is a widespread condition that appears to be increasing in prevalence and severity worldwide, yet the underlying mechanisms are not well understood. Recent research has identified various similarities between AD and autoimmune conditions, as well as indicating that there may be an association between AD and autoimmunity. This systematic review evaluates the association between AD and autoimmunity, as well as between severity of disease in AD and autoimmunity, with an emphasis on the associations with autoantibodies. MEDLINE (1946 to December 2017) and Embase (1974 to December 2017) databases were searched. Further relevant articles were retrieved from reference lists. Only studies measuring direct indicators of autoimmunity, in humans, were included. Qualitative analysis was carried out for all studies. In addition, quantitative analysis was used to evaluate prevalence of IgE autoantibodies and anti-nuclear antibodies (ANAs) in AD patients and control subjects. The Mantel-Haenszel method was used with a random-effects model. 28 studies assessed the occurrence of autoantibodies in AD patients and 16 studies were used to evaluate association between disease severity and autoantibodies. Pooled analysis from 14 studies, involving 986 AD patients and 441 control subjects, showed that IgE autoantibodies were significantly more prevalent in patients with AD (P < 0.00001) than control subjects. Similar analysis was carried out for ANAs, with eight studies that involved 1045 AD patients and 1273 control subjects. ANAs were significantly more prevalent in patients with AD (P = 0.003). This quantitative analysis supported an association between AD and IgE autoantibodies, as well as between AD and ANAs. There was insufficient data to make similar conclusions for other indicators of autoimmunity. The weight of evidence also suggests an association between IgE autoantibodies and disease severity. There was insufficient evidence to make this link for other indicators of autoimmunity.

β‐1,3‐glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area

“…Taken together, rAsp f 6 recognition possibly represents the signature of an autoimmune process against human MnSOD, occurring in at least a subset of patients affected by AD . The presence of autoantibodies of the IgE class and its association with disease severity has been suggested . In accordance with Mittermann et al, we also found a significantly higher frequency of IgE reactivity to Malassezia sympodialis rMala s 11 in severe AD, as a further confirmation of the presence of MnSOD reactivity in AD.…”

“…30 The presence of autoantibodies of the IgE class and its association with disease severity has been suggested. 31 In accordance with Mittermann et al, 32 we also found a significantly higher frequency of IgE reactivity to Malassezia sympodialis rMala s 11 in severe AD, as a further confirmation of the presence of MnSOD reactivity in AD.…”

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 ].…”

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

“…AD shows a strong genetic predisposition associated with epidermal barrier dysfunction and type 2 immune responses. The severity of the disease has been associated with allergen sensitization and IgE levels as well as with the prevalence of autoreactive IgE [ 1 , 2 , 3 , 4 , 5 ]. Dupilumab, which is a monoclonal antibody targeting the IL-4Rα chain, is approved to treat moderate to severe symptoms in children from six years old to adults, and is currently evaluated in toddlers from six months to five years old.…”

“…It is thought to be an essential part of its pathogenesis or of its chronification [ 28 , 40 ]. Two independent systematic reviews summed-up the relationship between AD, its severity, and autoreactive antibodies [ 4 , 5 ]. Autoreactive IgG with various specificities have been detected in multiple studies.…”