Walnut antigens may trigger autoantibody development in pemphigus vulgaris via “hit-and-run” mechanism

Abstract Background Environmental factors as well as genetic predisposition are known to be critical for the development of autoimmunity. However, the environmental agents that trigger autoimmune responses have remained elusive. One possible explanation is the "hit-and-run" mechanism where the inciting antigens that initiate autoimmune responses are not present at the time of overt autoimmune disease. Objective Following our previous findings that some allergens may incite autoimmune responses, we have investigated the potential role of environmental allergens in triggering autoantibody development in patients with an autoimmune skin disease, pemphigus vulgaris (PV). Methods Revertant/germline monoclonal antibodies (mAbs) (with mutations on variable regions of heavy and light chains reverted to germline forms) of eight anti-desmoglein 3 (Dsg3) pathogenic mAbs from PV patients were tested for reactivity against a panel of possible allergens, including insects, pollens, epithelia, fungi and food antigens. Results All the PV germline mAbs were reactive with antigens from walnut including a well-known allergen, Jug r 2, and an uncharacterized 85 kD protein component. Sera from PV patients contained significantly higher levels of anti-Dsg3 autoAbs than walnut-specific antibodies, suggesting that the autoreactive B cell response in PV may be initially triggered by walnut antigens, but is subsequently driven by Dsg3. Conclusion Our findings suggest that walnut antigens/allergens may initiate autoantibody development in PV via a "hit-and-run" mechanism. The revertant/germline mAb approach may provide a paradigm for the etiological study of other allergic and autoimmune diseases.