Cardiomyopathy and neuropathy are the two commonly observed complications in
diphtheria patients and in, some instances, individuals vaccinated against
diphtheria. The nature of these complications remains not well understood. It was suggested that autoimmunity may play a role in the development of these afflictions. Based on functional similarities between
diphtheria toxin (DT) and
epidermal growth factor receptor (EGFR), which both can bind to the
heparin-binding EGF-like growth factor (
HB-EGF) precursors, we suggested that
antibodies developed against DT can cross react with EGFR. Here, using serum from healthy donors (n = 10) and
diphtheria patients (n = 15), we demonstrated that B-subunit of DT has the antigenic
epitopes similar to those of EGFR.
Diphtheria toxin as well as EGFR could be recognized by
antibodies raised against EGFR and by serum
antibodies from
diphtheria patients. Moreover serum of
diphtheria patients competitively inhibits binding of anti-EGFR
antibodies to the receptor. The truncated
diphtheria toxin without B-subunit could be detected by serum
antibodies of
diphtheria patients, but not by anti-EGFR
antibodies. Collectively, these studies demonstrate cross-reactivity of
antibodies raised against B-subunit of DT and extracellular domain of EGFR and suggest that clinically observed post-
diphtheria complications may result from autoimmune inhibition of EGFR function and possible destruction of receptor-positive tissues.