Autoallergy: A pathogenetic factor in atopic dermatitis?

Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders

“…12,14 ± 22 While the origin of autoimmunity to intracellular proteins in atopic disorders is unknown, it is presumed that abnormal cell death triggered by environmental allergens or intrinsic factors in the target organs of atopy (skin, eyes, respiratory and gastrointestinal tracts) might facilitate the sustained exposure of potentially immunostimulatory forms of intracellular autoantigens to the immune system. 6,23 Consistent with this notion is that dysregulated keratinocyte apoptosis contributes to the development of the epidermal lesions associated with AD. 24,25 Along with Rosen and colleagues, we have shown systematically that many intracellular autoantigens targeted by autoantibodies in systemic autoimmunity undergo proteolytic cleavage during both apoptotic and non-apoptotic cell death.…”

“…This molecular mimicry scenario is supported by structural similarities between some environmental allergens and intracellular autoantigens targeted in AD. 6 A more likely scenario is that tissue damage and aberrant cell death triggered by environmental allergens or intrinsic factors in the target organs of atopy (skin, eyes, respiratory tract, and gastrointestinal tract) could contribute to the release and exposure to the immune system of intracellular antigens. 6,23 Apoptotic cells are considered reservoirs of potentially immunostimulatory forms of intracellular antigens.…”

“…6 A more likely scenario is that tissue damage and aberrant cell death triggered by environmental allergens or intrinsic factors in the target organs of atopy (skin, eyes, respiratory tract, and gastrointestinal tract) could contribute to the release and exposure to the immune system of intracellular antigens. 6,23 Apoptotic cells are considered reservoirs of potentially immunostimulatory forms of intracellular antigens. 31 ± 34 Massive apoptosis or defective clearance of apoptotic cells may lead to the accumulation of cells in late apoptotic stages or secondary necrosis, leading to the release of potentially harmful intracellular contents, such as proteases and pro-inflammatory signals, that could damage the surrounding tissue and provoke an inflammatory response.…”

Comparison of the Crystal Structures of the Human Manganese Superoxide Dismutase and the Homologous Aspergillus fumigatus Allergen at 2-Å Resolution

“…These data provide strong evidence for in vitro and in vivo humoral and cell-mediated autoreactivity to human MnSOD in patients allergic to A. fumigatus. IgE-mediated autoreactivity to self Ags is an emerging phenomenon that may contribute to exacerbation and/or perpetuation of severe atopic diseases in the absence of exogenous allergen exposure (16,17). To elucidate whether the mechanisms of these IgE-mediated autoimmune reactions are based on molecular mimicry between conserved B cell epitopes present on allergens and on the structurally related human counterparts, exact comparisons of the three-dimensional structure of the proteins are required.…”

Basophils and IgE: Linking the Allergic Environment to Autoimmunity

“…In both cases there can be manifestations that are associated with the production of autoantibodies and circulating immune complexes (CIC) formation [59]. Some studies have revealed a common structure of some allergens and autoantigens [60], with a developing hypothesis that many environmental allergens have common structural conformations with self-antigens [60]. This hypothesis could explain the development of certain autoimmune disease such as the chronic urticaria.…”