Volume 6 Supplement 1

24th European Workshop for Rheumatology Research

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

https://doi.org/10.1186/ar1080

Received: 16 January 2004

Published: 24 February 2004

Background

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.

Objective

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

Methods

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.

Results

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.

Conclusions

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]).

Declarations

Acknowledgement

Supported by grants of the DFG.

Authors’ Affiliations

(1)
Clinical Research Unit for Rheumatology, University Medical Center Freiburg
(2)
Institute for Biochemistry and Molecular Biology, University Freiburg
(3)
Institute for Organic Chemistry and Biochemistry, University Freiburg
(4)
Department of Internal Medicine, University Freiburg
(5)
Heart Center

References

  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

Copyright

© The Author(s) 2004

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