Food allergens could promote the Th2 mediated autoantibody development in an autoimmune skin disease bullous pemphigoid

Abstract

Abstract Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease and is characterized by the presence of autoantibodies (autoAbs) against skin hemidesmosomal adhesion molecules. The predominant antigenic target is the non-collagenous domain 16 (NC16A) of BP180. AutoAbs against NC16A lead to loss of adhesion and subsequent subepidermal blistering. It is unclear what triggers the development of autoAbs. Food allergens are known to induce T helper 2 (Th2) antibody responses and our previous studies have shown the possible role of environmental antigens/allergens in promoting autoAb development. The goal of this study is to investigate whether Th2 mediated immune responses against food allergens drive the autoAb development in BP. BP serum antibodies were tested against a panel of common environmental and food allergens. Anti-NC16A IgE and IgG4 monoclonal antibodies (mAbs) and their naïve counterparts were generated from a BP patient to determine their specificity or cross-reactivity. We found that antibodies from BP patients recognized food allergens, such as walnut, but not other types of allergens, such as insects, epithelia, fungi, or pollens. The levels of serum IgE and IgG4, but not IgG1, against selected food allergens were significantly higher than controls. The anti-NC16A IgE and IgG4 mAbs cross-reacted to food allergens, and their naïve mAb counterparts had reduced reactivity to NC16A, but still reacted strongly to food allergens. In addition, mice immunized with walnut allergen produced anti-NC16A antibodies. Our results indicate that Th2-associated autoAbs from BP subjects might be linked to antibody responses toward food allergens and may provide a target for the management and treatment of BP.