MPO-ANCA, PR3-ANCA without IF positivity may not be useful in diagnosing vasculitis
The detection of antiproteinase 3 or antimyeloperoxidase antibodies in serum antineutrophil cytoplasmic antibodies without positive cytoplasmic or perinuclear patterns detected with immunofluorescence is inconsistent and may be of limited use in the diagnosis of vasculitis, according to researchers.
The researchers studied patient records from Brigham and Women’s Hospital that included 2,345 samples sent for laboratory evaluation of serum antineutrophil cytoplasmic antibodies (ANCA) by both multiplex bead assays for antiproteinase 3 (PR3-ANCA) or antimyeloperoxidase antibodies (MPO-ANCA) and immunofluorescence (IF) between January 2011 and May 2013.
Results showed 1,998 of the samples with a negative IF, 147 showed an atypical IF, and 200 had a perinuclear or cytoplasmic pattern or both. In 2.5% of IF-negative samples from 38 patients, MPO-ANCA or PR3-ANCA were seen, whereas 62% of IF-positive samples contained MPO-ANCA or PR3-ANCA. Of MPO-ANCA- and/or PR3-ANCA-positive samples, 65% had a positive IF and 26% had a negative IF.
Samples positive for IF with a perinuclear pattern had higher concentrations of MPO-ANCA antibodies than IF-negative or atypical samples, whereas samples positive for IF with a cytoplasmic pattern had significantly higher PR3-ANCA antibody levels than IF-negative samples, according to the researchers. Nearly all samples with very high levels of MPO-ANCA and/or PR3-ANCA antibodies were positive on IF compared with antibodies in the IF-negative samples, which had very low levels of MPO-ANCA and/or PR3-ANCA.
Of the 38 patients identified with positive MPO-ANCA and/or PR3-ANCA antibodies, only one was IF-negative and diagnosed with ANCA-associated vasculitis (AAV) based on the presence of granulomatosis with polyangiitis in addition to positive MPO-ANCA antibody status.
Eleven of the IF-negative patients who showed positive MPO-ANCA or PR3-ANCA antibodies were previously diagnosed with AAV and had previously had positive IF results. Additionally, several patients had high levels of MPO-ANCA or PR3-ANCA antibodies and a negative IF result. Serial testing showed IF conversion from positive to negative, whereas MPO-ANCA or PR3-ANCA antibodies remained positive in three patients, and IF transitioned from positive to negative more rapidly than MPO-ANCA or PR3-ANCA antibody levels in five patients.
Some patients diagnosed with inflammatory bowel disease or systemic lupus erythematosus were IF-negative and MPO-ANCA- or PR3-ANCA-positive; however, a negative IF in patients with MPO-ANCA or PR3-ANCA antibodies negatively predicted the diagnosis of AAV by 97%, but the diagnosis was rarely new.
A strategy of ANCA evaluation with concurrent IF and antibody tests offers minimal advantage compared with reflex antibody tests of IF-positive samples, the researchers concluded. - by Shirley Pulawski
Disclosure: The researchers report no relevant financial disclosures.