Published online: May 6, 2019
Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease caused by IgG autoantibodies against the epidermal adhesion molecule desmoglein-3. As with other autoimmune diseases, both genetic and environmental factors are important for the development of PV. However, the environmental agents that promote autoantibody formation in PV are unknown.
In an article recently published in The Journal of Allergy and Clinical Immunology (JACI), Lin and colleagues investigated the potential role of environmental allergens in triggering autoantibody development in patients with PV. The investigators “reverted” pathogenic anti-desmoglein 3 monoclonal antibodies to their original germline forms, which allowed them to investigate the antigen specificity of the naïve B cell from which autoreactive B cells originated. The revertant antibodies were then screened for binding to a large panel of environmental and food allergens.
Surprisingly, the investigators found that all revertant antibodies showed strong reactivity to walnut allergen extract. The authors identified the allergen Jug r 2 and a previously uncharacterized walnut protein, methytransferase-like protein, as the primary targets for the revertant antibodies. Titration studies demonstrated that revertant antibodies had greater affinity for walnut than desmoglein-3, whereas the opposite was observed for pathogenic autoantibodies. Thus, while autoreactive B cells may have been initially stimulated by walnut antigen, the subsequent development of high-affinity autoantibodies appeared to be driven by recognition of endogenous desmoglein-3 antigen.
In summary, this study provides evidence that walnut antigens may promote autoantibody production in PV through a “hit and run” mechanism. In this model, walnut proteins may be the initial antigenic trigger for B cell activation, but do not drive the continued expansion of autoreactive B cells. While further studies are needed to confirm an association between walnut exposure and PV development, these findings suggest that walnut allergens have the potential to trigger autoantibody formation in genetically susceptible individuals.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.