Human anti-FcεRIα autoantibodies isolated from healthy donors cross-react with tetanus toxoid

Natural antibodies (Ab) reacting with self antigens have been shown to be present in all individuals. These autoantibodies (auto-Ab) can be either pathogenic or non-pathogenic. Auto-Ab reacting with the α-subunit of the high-affinity receptor for IgE (FcϵRIα) have been implicated in the pathogenesis of a subset of patients with chronic idiopathic urticaria (CIU). Intravenous immunoglobulin (IVIg) preparations have been used with variable clinical benefit in the treatment of these patients. Here we show that anti-FcϵRIα auto-Ab are present in a therapeutic IVIg preparation as well as in atopic and chronic urticaria patients and healthy individuals. We affinity-purified the anti-FcϵRIα Ab from an IVIg preparation using recombinant FcϵRIα. Interestingly, these anti-FcϵRIα auto-Ab showed no evidence of histamine release but strongly cross-reacted with an external antigen, tetanus toxoid (TTd) with a higher affinity for TTd than for the FcϵRIα. Since the cross-reacting Ab are non-anaphylactogenic, there is no evidence that TTd immunization may contribute to the pathogenesis of CIU. However, our results may indicate that the anti-FcϵRIα auto-Ab belong to the natural Ab and serve as the parental Ab for some anti-TTd Ab.