ANCA in the diagnosis of neutrophil-mediated inflammation.

Inconsistencies in ANCA (anti-neutrophil cytoplasm autoantibodies) and other NSA (neutrophil-specific autoantibodies) terminology frequently cause incorrect indications, choices, applications and interpretations of ANCA diagnostics in routine practice, except for ANCA-associated vasculitis. A review of the current knowledge and the authors' personal experiences based on routine assessments of ANCA and other NSA are documented and presented. A better understanding of the principles and mechanisms of ANCA and other NSA responses and determination, as well as unification of their terminology could result in improvements in indications, applications and the interpretation of ANCA diagnostics in diseases other than vasculitis, especially in IBD (inflammatory bowel diseases), AILD (autoimmune liver diseases), CTD (connective tissue diseases) and other chronic neutrophil-mediated inflammatory diseases.

Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes.

Translocation of intracellular components to the cell surface during the priming or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for interaction of antineutrophil cytoplasmic antibodies (ANCA) with these antigens. To test the capacity of apoptotic PMN to trigger production of ANCA, six groups of mice were immunized with either live or apoptotic lymphocytes, or with live, apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and apoptotic neutrophils developed high titers of antibodies which gave a granular cytoplasmic immunofluorescent pattern. These antibodies were specific for lactoferrin and myeloperoxidase. Following a second intravenous infusion of apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not found in mice which developed ANCA. The ANCA-containing IgG fraction induced superoxide production by human PMNs. These results support the hypothesis that neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may induce ANCA in the proper conditions.