Atypical C-ANCA following high dose intravenous immunoglobulin

Aims-(1) To assess a range of intravenous immunoglobulin products for atypi cal classical antineutrophil cytoplasmic antibody (C-ANCA) staining and to determine if this is present in patients treated with high dose intravenous immunoglobulin (2 g/kg/month) and replacement doses (200 mg/kg fortnightly ); (2) using the United Kingdom national external quality assessment scheme (NEQAS), to determine if laboratories could differentiate this pattern fro m classical ANCA. Methods-ANCA testing was performed on 30 batches of intravenous immunoglobu lin from several manufacturers. Six patients treated with high dose intrave nous immunoglobulin and 11 receiving replacement doses of immunoglobulin fo r hypogammaglobulinaemia were tested for ANCA by indirect immunofluorescenc e on cytospin preparations of ethanol fixed neutrophils and by enzyme linke d immunosorbent assay (ELISA). One of the positive immunoglobulin batches w as tested blindly by 125 laboratories involved in NEQAS by indirect immunof luorescence and by ELISA in some laboratories. Results-16 of 31 batches of intravenous immunoglobulin from six different m anufacturers were atypical C-ANCA positive. Three of six patients receiving high dose intravenous immunoglobulin and none of 11 patients on replacemen t doses were atypical C-ANCA positive. The results of the NEQAS assessment by indirect immunofluorescence were 68% C-ANCA positive, 17% negative, 9% a typical C-ANCA and 6% P-ANCA. Conclusions-Some but not all intravenous immunoglobulin products yield a po sitive atypical cANCA by indirect immunofluorescence. An identical pattern may be observed in patients receiving high dose intravenous immunoglobulin but not in those on replacement doses. Of laboratories participating in NEQ AS, 68% reported this pattern as cANCA. This reinforces the importance of r eporting only "classical ANCA," defined by international ANCA workshops, to maintain the specificity of ANCA immunofluorescence and its close disease associations.