Classes and subclasses of anti-neutrophil cytoplasmic antibodies (ANCA) in ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibodies (ANCA) are important in both pathogenesis and diagnosis of granulomatosis with poly-angiitis (GPA) and other ANCA-associated vasculitis (AAV). Autoantibodies have been shown before disease onset in other auto-immune diseases. During the course of disease, antibodies switch class and subclasses. The objective of this study is to investigate switching of immunoglobulin classes and subclasses of ANCA in different stadia of GPA. A follow-up study of ANCA-positive sera was done to identify asymptomatic ANCA-positive sera. An insufficient number of sera were found appropriate for a longitudinal study. 9 GPA patients with disease limited to ear, nose and throat (ENT) and 10 GPA patients with renal involvement were included in a transversal analysis. Presence of IgG1- and IgG4-ANCA was investigated with indirect immunofluorescence (IIF) and IgA-ANCA was investigated using capture enzyme-linked immunosorbent assay (ELISA). IgG1- and IgG4-ANCA were found in 4 systemic GPA patients. In 1 ENT-limited GPA patient IgG4-ANCA was also shown. IgA-anti-PR3 ANCA were found in 3 systemic GPA patients, IgA-anti-MPO ANCA were found in 2 systemic GPA and 1 ENT-limited GPA patient. IgA-ANCA was associated with ENT-involvement and elevated serum IgA. No relation was observed in other organ involvement or duration of disease. IgA-ANCA directed to PR3 or MPO in GPA patients were demonstrated. These antibodies may occur due to chronic ENT-inflammation. Future studies are required to investigate possible mechanisms of alterations in ANCA pathogenicity during the course of AAV.