ANCA Status or Clinical Phenotype — What Counts More?

Abstract

Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study

“…This may reflect the more chronic, smoldering course of MPO-ANCA disease, compared to the acute but relapsing nature of PR3-ANCA. 14 , 31 , 32 This finding is further supported by a study done by Basu et al., 33 where, in the supplementary data, it was shown that patients who are MPO-ANCA positive, were more likely to have higher rates of fatigue than MPO-ANCA negative patients (p = 0.05). In contrast, patients who were currently PR3-ANCA positive did not have higher rates of fatigue than PR3-ANCA negative patients did (p = 0.47).…”

Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission

“…This might reflect differences in pathogenesis between both entities. Several independent investigations have found a higher relapse rate among individuals with PR3- as compared with MPO-ANCA vasculitis 1. Serum PR3-ANCA positivity and increasing titres of PR3-ANCA during follow-up were each associated with relapse in several studies 5 35.…”

“…Serum PR3-ANCA positivity and increasing titres of PR3-ANCA during follow-up were each associated with relapse in several studies 5 35. Notably, only few patients with MPO-ANCA vasculitis relapsed during the follow-up of the RAVE trial, and MPO-ANCA vasculitis usually presents at older age and with impaired kidney function, which may have been negative predictors of relapses 1. Findings concerning baseline sICPs as predictors for relapse under RTX treatment in MPO-ANCA vasculitis were limited by the lower numbers, but in part followed the trend shown in the substantially larger PR3 ANCA vasculitis cohort.…”

“…ANCA-associated vasculitis (AAV) is characterised by distinct clinical phenotypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis and can further be distinguished by the presence of either antibodies to proteinase 3 (PR3) or myeloperoxidase (MPO) 1. In spite of improved management and new therapies, up to 38% of patients with AAV fail to achieve remission at 6 months2 and up to 89% experience a relapse at 5 years of follow-up,3 depending on the definition of remission and the therapies used to maintain remission and the duration thereof.…”

Global epidemiology of vasculitis

“…The widespread adoption of the 1994 Chapel Hill Consensus definitions for vasculitis resulted in the recognition of MPA as an entity distinct from polyarteritis nodosa 6 . With the acknowledged imperfections of the ACR and Chapel Hill Consensus criteria for classification, there has been debate as to whether it is preferable to classify patients by ANCA serotype (proteinase 3 and myeloperoxidase (MPO)) alone rather than by the clinical phenotype 108 . It is hoped that the new EULAR–ACR classification system, which incorporates ANCA status, will help to resolve this debate 8 – 10 .…”