[Molecular mimicry between neurofilaments and titin as the basis for autoimmunity towards skeletal muscle in paraneoplastic myasthenia gravis].
OBJECTIVE
Autoantibodies against striated muscle proteins, particularly titin, characteristically distinguish thymoma-associated from non-paraneoplastic myasthenia gravis (MG) patients. However, the stimulus for this autoimmunity remains enigmatic since whole titin is not detectable in these tumors. Since Neurofilaments (NF) contain titin epitopes, MG-associated thymomas were investigated for NF expression using immunohistochemistry and Western blotting.


RESULTS
In thymomas with cortical differentiation many of the neoplastic epithelial cells expressed medium molecular weight NF at the protein level. In sharp contrast, in medullary and mixed thymomas and in normal thymuses immunoreactivity with anti-NF antibodies was rare.


CONCLUSIONS
The overexpression of NFs with titin epitopes by neoplastic cells in an inappropriate cortical environment may be the basis for the autosensitization of developing T-cells against titin in MG-associated cortical type thymomas.
Wilisch
A
A
Institut für Pathologie, Universität Würzburg.
Schultz
A
A
Greiner
A
A
Kirchner
T
T
Müller-Hermelink
H K
HK
Marx
A
A
D001323:Autoantibodies; D064211:Connectin; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D009124:Muscle Proteins / Q000032:analysis / Q000276:immunology*; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000276:immunology* / Q000473:pathology; D011494:Protein Kinases / Q000032:analysis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000032:analysis / Q000276:immunology; D013945:Thymoma / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D064211:Connectin; D008565:Membrane Proteins; D009124:Muscle Proteins; D016900:Neurofilament Proteins; D011950:Receptors, Cholinergic; C577285:TTN protein, human; D011494:Protein Kinases
Molekulares Mimikry zwischen Neurofilamenten und Titin als Grundlage der Autoimmunität gegen Skelettmuskulatur bei paraneoplastischer Myasthenia gravis.