Precision Therapy of ANCA Vasculitis

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Villacorta J., Martinez-Valenzuela L., Martin-Capon I., Bordignon-Draibe J.: Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach. Nephron DOI 10.1159/000520727

Individualized (precision) therapy of ANCA-associated vasculitis (AAV) is a goal that will likely improve long-term outcomes of this very pathogenically heterogenous and clinically variable disorder. Genetics, environment, and serology contribute to the spectrum of clinical presentations and course of the group of disorders covered under the generic heading of AAV. They are presently divided into anti-proteinase 3 (aPR3) and anti-myeloperoxidase (aMPO) antibody subsets. A fraction (about 20%) will have concomitant anti-GBM, and rarely both aPR3 and aMPO may coexist. A major question is whether the approach to treatment is the same regardless of the phenotype or whether an opportunity exists to individualize therapy based on clinical, pathologic, genetic, or serological sub-categorization to improve outcomes (precision medicine).

Villacorta and colleagues address this question with a scholarly review of AAV and conclude that serological biomarkers (aPR3 and aMPO) can be used effectively to construct individually specific regimens of immunosuppressive/anti-inflammatory therapy (mainly focused on avoidance of relapse). Whether genetic analysis, novel biomarkers (urinary CD163, MCP1), complement activation profile, or deep morphologic phenotyping will allow even more refinement of individualized treatment of AAV remains uncertain. The role of biomarkers to help determine the potential efficacy of plasma exchange (PLEX) also remains uncertain. Clearly, patients with concomitant AAV and aGBM require very specific approaches to therapy, which frequently involve timely use of PLEX.

Overall, this report is a valuable and quite contemporary addition to the literature on this complex topic. Some might claim that a “multi-omic” analysis of AAV might provide an even more thorough sub-categorization and a standardized precision medicine approach to management of all patients with AAV, but I think that this goal is presently elusive.

Richard Glassock

Quoted Karger Article

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach