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

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]).