IMMUNOLOGICAL SIMILARITY OF DIPHTHERIA TOXIN AND EGF RECEPTOR
V. Yu. Alexeyev,1 O. K. Kaboev,2 O. G. Scherbakova,3 E. V. Semenova,2
M. V. Filatov 2
1 Department of Dermatology and Cutaneous Biology, Thomas Jefferson University,
Jefferson Vaccine Center, Philadelphia, USA,
2 Molecular and Radiation Biophysics Division of St. Petersburg Nuclear Physics Institute RAS,
St. Petersburg, Gatchina, Russia,
and 3 Department of Molecular and Cellular Physiology, Stanford University, Stanford, USA;
1 e-mail: filatov@omrb.pnpi.spb.ru
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.
Key words: diphtheria toxin, epidermal growth factor receptor, cross-immunoreactivity, post-diphtheria complications
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