High proteinase 3 (PR3)/myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) titers can be used to clinically differentiate between ANCA-associated vasculitis (AAV) and other disorders with a similar presentation, according to a study published in RMD Open.

AAV is an umbrella term for various diseases, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Recently, international bodies have placed a greater emphasis on PR3 or MPO to classify GPA and MPA, respectively. These thresholds can raise appropriate clinical suspicion regarding the underlying disease of a vague presentation, especially if the typical diagnostic workup yields little relevant information. 

Studies on AAV are severely limited due to the rarity of this condition. However, based on the evidence available in the medical literature, Merindol and colleagues hypothesized that the probability of AAV is higher in the presence of high ANCA titers. They thus set out to investigate the relevance of ANCA titers in discriminating between AAV and its closest mimickers and investigate if a titer cut-off point can be extrapolated to be used in clinical settings. 

The research team conducted a retrospective observational study including patients with ANCA-positive assays at the University Hospital of Nice, France. The immunology laboratory of the hospital had a database that allowed the researchers to search for adult patients with 1 or more positive MPO-ANCA and/or PR3-ANCA tests. ANCA-positive patients were divided into 3 groups: patients with confirmed AAV, those with a non-AAV autoimmune disorder, and individuals without any relevant autoimmune features. The authors of the study then performed statistical analysis on these groups of patients. 

Read more about AAV etiology 

Over the course of the study period that spanned 8 years (from 2010 to 2018), 13,481 ANCA studies were performed, 2.9% of which were positive. Two hundred eighty-eight ANCA-positive patients were included in the final analysis, including 49 in the AAV group—33 with MPA and 16 with GPA. 

The authors reported that a high ANCA titer can be clinically useful in differentiating between AAV and their mimickers, regardless of PR3 or MPO targets. Their findings strengthen the case that ANCA titers can be used to distinguish between alternative diagnoses, such as nonvasculitide inflammatory disease, non-AAV vasculitides, and infection. They also proposed an ANCA titer cut-off of 65 U/mL to help physicians correctly reclassify patients.

“Prospective studies validating an ANCA-titre threshold-based approach might help clinicians to better discriminate between AAV and alternative diagnoses,” the authors concluded. 


Merindol J, Levraut M, Seitz-Polski B, Morand L, Martis N. Diagnostic significance of antineutrophil cytoplasmic antibody (ANCA) titres: a retrospective case-control studyRMD Open. Published online April 13, 2023. doi:10.1136/rmdopen-2023-003113