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Arthritis Research & Therapy

Open Access

Autoreactive T cells specific for a natural intracellular hapten: an example from patients with acute myocarditis and possible consequences for other inflammatory diseases

  • I Melchers1,
  • G Cicek2,
  • E Schiltz3,
  • J Staiger4,
  • F-J Neumann5 and
  • R Brandsch2
Arthritis Res Ther20046(Suppl 1):38

Received: 16 January 2004

Published: 24 February 2004


PeptideAmino Acid SequenceTrypsinAdeninePeripheral Blood Mononuclear Cell


All organisms contain naturally occurring haptens in the form of enzyme cofactors bound covalently to apoproteins. One example is flavine adenine dinucleotide (FAD). Autoantibodies recognizing flavoproteins, with specificity for flavin or flavin-peptide were described in patients with myocarditis or other muscular diseases.


We wanted to test the hypothesis that FAD-peptide reactive T cells exist in patients with acute myocarditis.


Peripheral blood mononuclear cells (PBMNC) were tested in vitro with a purified FAD-peptide (from a trypsin digested, affinity purified flavoprotein) or a synthetic peptide with the same amino acid sequence. Proliferation was measured by 3H-TdR incorporation, and the secretion of IFN-γ by ELISA.


PBMNC from four patients with acute myocarditis showed positive responses to the FAD-peptide, in contrast to control individuals. The synthetic FAD-free peptide did not induce a response.


The results are consistent with the hypothesis that during the inflammation of the heart cardiomyocytes liberate normally cryptic mitochondrial FAD-peptides, which induce a T cell response. Similar mechanisms could be envisaged in inflammatory diseases of other compartments (e.g. the joints in rheumatic diseases [1]).



Supported by grants of the DFG.

Authors’ Affiliations

Clinical Research Unit for Rheumatology, University Medical Center Freiburg, Germany
Institute for Biochemistry and Molecular Biology, University Freiburg, Germany
Institute for Organic Chemistry and Biochemistry, University Freiburg, Germany
Department of Internal Medicine, University Freiburg, Germany
Heart Center, Bad Krozingen, Germany


  1. Cicek G, Schiltz E, Staiger J, Neumann F-J, Melchers I, Brandsch R: Specific stimulation of peripheral blood mononuclear cells from patients with acute myocarditis by peptide-bound flavin adenine dinucleotide (FAD), a naturally accurring autologous hapten. Clin Exp Immunol. 2003, 132: 366-370. 10.1046/j.1365-2249.2003.02130.x.PubMed CentralView ArticlePubMedGoogle Scholar


© The Author(s) 2004