Anticytokeratins are a potential source of false-positive indirect immunofluorescence assays for C-ANCA.
Antibodies to neutrophil cytoplasmic antigens (ANCA) targeted toward granule enzymes have been recognized as a valuable diagnostic tool in the detection of Wegener's granulomatosis and systemic vasculitides. However, the most commonly used method of detection, the indirect immunofluorescence assay, is prone to false-positive results due to antibodies of different pathological significance either targeted to, or cross-reacting with, similarly distributed epitopes. Using double immunofluorescence, the present study demonstrates that anticytokeratin antibodies are able to produce false-positive C-ANCA immunofluorescence assays. In addition, a case of natural appearance of cytokeratin-reactive antibodies causing a false-positive "pseudo-ANCA" staining pattern in a patient presenting with sepsis is reported. Since the expression of cytokeratins is almost exclusively confined to epithelial cells, the most plausible explanation for both phenomena is a crossreaction of anticytokeratin antibodies with granule associated epitopes. Due to the natural appearance of anticytokeratin antibodies in association with a variety of other pathologic entities, it is of crucial importance for the diagnostic significance of the C-ANCA immunofluorescence assay to exclude anticytokeratin caused false-positive results. It is shown that supplementary indirect immunofluorescence tests performed on cultured human epithelial cells readily distinguish anticytokeratin caused "pseudo-ANCA" from true C-ANCA.
Streicher
J
J
Department of Anatomy, University of Vienna, Austria. Johannes.Streicher@univie.ac.at
Fabian
B
B
Herkner
K
K
Pointner
H
H
Bayer
P M
PM
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007633:Keratins / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D007633:Keratins