ANTICYTOKERATINS ARE A POTENTIAL SOURCE OF FALSE-POSITIVE INDIRECT IMMUNOFLUORESCENCE ASSAYS FOR C-ANCA

Antibodies to neutrophil cytoplasmic antigens (ANCA) targeted toward g ranule enzymes have been recognized as a valuable diagnostic tool in t he detection of Wegener's granulomatosis and systemic vasculitides. Ho wever, the most commonly used method of detection, the indirect immuno fluorescence assay, is prone to false-positive results due to antibodi es of different pathological significance either targeted to, or cross -reacting with, similarly distributed epitopes. Using double immunoflu orescence, the present study demonstrates that anticytokeratin antibod ies are able to produce false-positive C-ANCA immunofluorescence assay s. In addition, a case of natural appearance of cytokeratin-reactive a ntibodies 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 an ticytokeratin 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 th at supplementary indirect immunofluorescence tests performed on cultur ed human epithelial cells readily distinguish anticytokeratin caused ' 'pseudo-ANCA'' from true C-ANCA. (C) 1998 Wiley-Liss, Inc.