Work

Concurrent Anti-PR3 Immunoassay and cANCA Indirect Immunofluorescence Testing Provide Complementary Information for Clinical Laboratory Detection of Antineutrophil Cytoplasmic Antibodies

Year: 2025

Type: article

Abstract: BACKGROUND: Multiplex immunoassays and indirect immunofluorescence assays (IFA) are frequently used for the detection of antineutrophil cytoplasmic antibodies (ANCA) but can produce differing results. METHODS: To understand the settings in which discordant results occur, we retrospectively investigated first-recorded cytoplasmic ANCA (cANCA) IFA and antiproteinase 3 (PR3) results (n = 15 772) generated over 4 years in our clinical laboratory. RESULTS: We detected significant bidirectional disagreement between cANCA and anti-PR3-antibody results that was not immunoassay or instrument specific. Sixteen percent (22/139) of cANCA-positive specimens were negative for anti-PR3 by multiplex immunoassay. Similarly, 61% (175/285) of anti-PR3 positive specimens were negative for cANCA by IFA. Borderline or indeterminate positivity thresholds could not fully explain the discrepancy between results, suggesting that patient-associated characteristics may contribute. Medical record review of patients with discordant testing over time revealed cANCA/anti-PR3 disagreement in patients with ANCA-associated vasculitis on chronic immunomodulatory therapy, suggesting a treatment-related phenomenon. Among 59% (13/22) of patients for whom serial ANCA testing was evaluated, cANCA semiquantitative titers and anti-PR3 antibody quantitative results trended together and correlated with disease activity in response to immunomodulatory therapy. However, asynchronous changes were observed in 41% (9/22) of patients, leading to significant differences in anti-PR3 or cANCA results despite sustained cANCA or anti-PR3 antibody negativity, respectively. CONCLUSION: In certain individuals, anti-PR3 antibodies and cANCA titers may differentially capture disease activity, and cANCA/anti-PR3-discordant results may have clinical significance in the setting of immunomodulatory therapy. Our data argue for a complementary testing approach that implements both immunoassay and IFA methods to detect these changes over time.

Source: The Journal of Applied Laboratory Medicine

DOI: 10.1093/jalm/jfaf168

Authors: Reagan Badger, Susan L Fink, Kathleen Hutchinson, Mark H Wener, Chihiro Morishima, Rebecca S Treger

Institutions: University of Washington, University of Washington Medical Center

Language: English

Topic: Vasculitis and related conditions

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,212