Anti‐cardiolipin antibodies in atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease with a complex, multifactoral etiology, probably caused by concerted actions of environmental and genetic factors (1, 2). An additional relevance of bacterial superantigens is discussed (3, 4). The disease is characterized by a number of immunological abnormalities. Cell-mediated immune hyperactivity, elevated IgE serum levels and the presence of eosinophil-derived mediators are well known features (5). In this issue Szakos et al. (6) present a further immunological abnormality in AD patients. The authors report an association between the occurrence of anticardiolipin immunoglobulin (Ig)M and mite allergenspecific IgE antibodies in children with extrinsic type of AD. While detection of mite allergen-specific IgE is a typical feature of AD, anticardiolipin antibodies are reported especially in autoimmune diseases, e.g. in antiphospholipid syndrome (APS) or in patients suffering from systemic lupus erythematosus (SLE) (7). Szakos et al. hold mite proteins responsible for inducing specific anti-mite IgE and mite-lipids for provoking antibodies of the antiphospholipid-type antibodies, similar to the situation when lipids of microorganisms are initiating the production of anticardiolipin IgM during infections. At first glance, this association between a typical feature of AD and a typical feature of systemic autoimmune disease astonishes, because clinical findings and genetic background of AD and autoimmune disorders are totally different. However, a few earlier studies revealed some common features between AD and SLE, a classical multiorgan autoimmune disease, e.g. elevated levels of antinuclear antibodies (8). Furthermore, both AD and SLE are mainly characterized by a predominance of Th2-type cytokines (while some Th1-type cytokines [interleukin (IL)2, interferonc] might play an additional role in inflammatory skin lesions). Both disorders present elevated levels of pathologic autoantibodies, in AD predominately allergen-specific antibodies of the IgEtype and in SLE predominately IgGor IgM-type antibodies targeting nuclear proteins (5, 9). Anti-cardiolipin antibodies (CLA) are reported in several clinical disorders including autoimmune, infectious and malignant diseases, as well as recently in AD (10). However, thrombosis and recurrent fetal loss associated with CLAs, constituting the APS are reported in autoimmune patients only, especially in patients suffering from SLE (7). b2-Glycoprotein (b2 GPI) appears to be the major antigen for CLA. It is a highly conserved protein, with more than 80% homology between the amino sequences of human, bovine and rat counterparts (11). Therefore, nutritional contact of infant AD patients with b2 GPI in milk and meat may lead to the generation of antibodies targeting the bovine as well as the human anti-b2 GPI. A high frequency of IgG anti-b2 GPI was found in patients with AD, but not in those with other allergic diseases. These anti-b2 GPIs showed an epitope difference to the anti-b2 GPI found in APS what may explain the nonthrombogenicity of these antibodies seen in children with AD (10). The cause of specific antibody-production in AD and SLE is not yet clear. Probably, besides the contact with a corresponding antigen, additional immunoregulative factors are needed for their generation. In this context, especially an overexpression of Th2-type cytokines (e.g. IL4, IL5, IL0 and IL13) seems to be relevant. The Th2 cytokines are not only undeniable factors of antibody-generation by B-cells, furthermore we know some examples of pathologically elevated antibodyJ. Wenzel, Th. Bieber Department of Dermatology, University of Bonn, Germany