Human anti-Fc epsilon RI alpha autoantibodies isolated from healthy donorscross-react with tetanus toxoid

Natural antibodies (Ab) reacting with self antigens have been shown to be p resent in all individuals. These autoantibodies (auto-Ab) can be either pat hogenic or non-pathogenic. Auto-Ab reacting with the alpha-subunit of the h igh-affinity receptor for IgE (Fc epsilon RI alpha) have been implicated in the pathogenesis of a subset of patients with chronic idiopathic urticaria (CIU). Intravenous immunoglobulin (IVlg) preparations have been used with variable clinical benefit in the treatment of these patients. Here we show that anti-Fc epsilon RI alpha auto-Ab are present in a therapeutic IVIg pre paration as well as in atopic and chronic urticaria patients and healthy in dividuals. We affinity-purified the anti-Fc epsilon RI alpha Ab from an IVI g preparation using recombinant Fc epsilon RI alpha. Interestingly, these a nti-Fc epsilon RI alpha auto-Ab showed no evidence of histamine release but strongly cross-reacted with an external antigen, tetanus toroid (TTd) with a higher affinity for TTd than for the Fc epsilon RI alpha. Since the cros s-reacting Ab are non-anaphylactogenic, there is no evidence that TTd immun ization may contribute to the pathogenesis of CIU. However, our results may indicate that the anti-Fc epsilon RI alpha auto-Ab belong to the natural A b and serve as the parental Ab for some anti-TTd Ab.