Heterogeneity of ANCA sera showing atypical, peripheral and classical cytoplasmic immunofluorescence patterns

Atypical (A) ANCA immunofluorescence (IF) patterns have been described in several disease groups. We have previously reported a distinct cytoplasmic A-ANCA in 7-10% of patients with SLE and/or RA. Here, we show that these rheumatic disease associated A-ANCAs are best identified using U937 cells as substrate and that they do not target either a serine proteinase or a peroxidase. Furthermore, these sera immunoprecipitate a 40 kDa or a 42 kDa band using in vivo 35S-amino acid labelled HL60 or U937 cell extracts, respectively. Although these bands are the only one seen with pure A-ANCA sera, they can also be found in addition to the expected bands of PR3 or MPO in up to 30% of bona fide C- or P-ANCA sera. These data confirm and extend our previous observations. They also suggest that target heterogeneity of ANCA antibodies is frequent. Care should thus be taken in interpreting in a cause and effect relationship, an IF pattern or a biological effect produced by a serum with ill documented monospecificity. The exact nature and significance of this (these) new antigen(s) have yet to be clarified.