NEUTROPHIL CYTOPLASMIC ANTIBODIES (P-ANCA) IN ULCERATIVE-COLITIS

Aims-To study ulcerative colitis associated neutrophil cytoplasmic ant ibodies (p-ANCA) in respect of class and subclass distribution, antige n specificity, and (sub)cellular localisation of the antigen(s) to whi ch these antibodies are directed. Methods-p-ANCA positivity was determ ined using the standard indirect immunofluorescence test (IIFT). The i mmunoglobulin (Ig) subclass distribution of p-ANCA was investigated us ing monoclonal antibodies directed against IgG1, IgG2, IgG3, and IgG4. Intracellular antigen localisation studies were performed on (fractio nated) neutrophils using antigen-specific antibodies. Results-In contr ast to vasculitis associated ANCA, ulcerative colitis p-ANCA are mainl y of IgG1 and IgG3 subclass and lack IgG4. Ulcerative colitis p-ANCA a re myeloid specific. IIFT data indicate that the related antigen(s) se em(s) to be located not in the cytosol, but in the granules (most like ly the azurophil granules) of the neutrophil. Conclusions-p-ANCA in ul cerative colitis have a different immunoglobulin subclass distribution than the ANCA of systemic necrotising vasculitis and necrotising and crescentic glomerulonephritis. This may point to differences in immune regulation between these diseases. Both cathepsin G and lactoferrin a re recognised by a subpopulation of ulcerative colitis p-ANCA. In our series, eight out of 36 (22%) of ulcerative colitis associated p-ANCA react with lactoferrin and seven (19.5%) other sera with cathepsin G. None of them recognised both antigens. The main target antigen(s) of u lcerative colitis p-ANCA still remain(s) to be identified.