Case 1: For example, an 84-year-old woman presented with nonspecific interstitial infiltrates. Her ANCA test results were negative for C-ANCA and P-ANCA but positive for PR3, and MPO was a negative mismatch. Clinically, the positive PR3 result was a low pretest probability for granulomatosis with polyangiitis (Wegener’s), which warranted further investigation. After looking into the laboratory—which had changed its assay as a result of regular quality testing—the next step was to use a backup methodology to troubleshoot the test result. A high-sensitivity antigen-specific assay—direct ELISA—was used at the time, but Dr. Specks noted that he would use the microsphere assay today. Follow-up testing with immunofluorescence indicated the absence of PR3 antibodies. This case demonstrates a methodologically false-positive test result that should be ignored in this clinical setting, Dr. Specks added.
Case 2: In another example, a 55-year-old man presented with destructive nasal disease and hearing problems. He had no systemic symptoms and no other evidence of vasculitis. Testing came back with a mismatch: positive for P-ANCA and PR3-ANCA but negative for MPO-ANCA. In this case, the patient history indicated cocaine-induced midline destructive lesions (CIMDL), which mimics granulomatosis with polyangiitis (Wegener’s) with more severe local destruction, fewer systemic symptoms, and no other organs being involved. CIMDL is also associated with positive P-ANCA and negative MPO-ANCA tests, and possibly positive PR3-ANCA tests.
“Unfortunately the cocaine story over the last few years has gotten more complex with levamisole as a contaminant,” Dr. Specks said. High-titer MPO-ANCA results are associated with levamisole use.
The conclusion for the diagnosis of ANCA-associated vasculitis, Dr. Specks said, is that “single-modality testing will get you into trouble” because it can provide misleading results. If anything other than matching pairs are determined, troubleshooting is necessary.
Serial Testing to Predict Relapses
In addition to being a diagnostic tool for vasculitis, ANCA testing may be useful for predicting relapses and guiding treatment. There is some evidence to suggest that ANCA levels correlate with disease activity. It probably doesn’t matter which method is used for serial ANCA testing, as long as the same test is used consistently for the same patient, Dr. Specks said.
Dr. Specks and his team conducted a study of serial ANCA testing to determine whether PR3-ANCA decreases are associated with a shorter time to sustained remission, and whether PR3-ANCA increases predict relapses.1 They collected samples every three months and analyzed all samples using capture ELISA methods. The researchers found that patients who had a decrease in PR3-ANCA levels had faster time to complete sustained remission than those who didn’t have a decrease during treatment, although the result did not reach statistical significance, Dr. Specks said.
