Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center

Abstract

Objective Antineutrophil cytoplasmic antibodies (ANCAs) are considered a risk factor for granulomatosis with polyangiitis (GPA) exacerbation, especially when staphylococcal superantigens (SAgs) are present in nasal swabs. Their role in monitoring disease activity remains controversial. This study determined the relationship of ANCAs with disease activity and presence of SAgs in GPA patients. Methods Among a total of 115 GPA patients hospitalized in the period 2009-2016, we investigated the presence of SAgs and ANCA concentration. Blood samples and nasal swabs were taken at each visit (referred further to as episodes). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). Results We analyzed 362 episodes. ANCAs were detected in 215 (59.4%), while SAgs were detected in 126 (34.8%) episodes. We found a significant correlation between the presence of ANCAs and disease activity (p = 0.0032), as well as between their level and GPA severity (r = 0.25363, p = 0.000001). We also determined that an ANCA values ≥ 138 Ru/ml were an indicator of active disease with high specificity and low sensitivity (84.4% and 37.3%, respectively). The relationship between ANCA presence and the presence of SAgs was not confirmed; however, when SAgs were analyzed based on the different types, ANCA levels were found to be significantly higher in the group with SAg type B (p = 0.031). Conclusions There was no detectable evidence for the association between ANCA level and the presence of SAgs. Although monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone. Key Points • ANCA concentration usually correlates with GPA activity, although in half of patients, ANCAs persist despite effective treatment and clinical remission. • ANCA values of 138 Ru/ml seem to be an indicator of active disease with high specificity, but low sensitivity. • Although there is a relevance for ANCA monitoring as a marker of disease activity, GPA management cannot be based on ANCA levels alone. • The suspected clinical correlation between ANCA formation and SAg presence in nasal swabs is not obvious and requires further investigations.

Biomarkers in ANCA-Associated Vasculitis: Potential Pitfalls and Future Prospects

“…A subsequent meta-analysis by Tomassen et al was more stringent in its study selection, identifying a modest association at best for persisting ANCA positivity or rising titres with the risk of relapse (17) . Several studies with more longitudinal data, including follow up data from large trials, have since corroborated earlier findings that persistent ANCA positivity, ANCA reappearance and the presence of anti-proteinase 3 (PR3) antibodies are risk factors for relapsing disease (18)(19)(20)(21)(22)(23)(24) . Similarly, seronegativity following remissioninduction therapy is associated with a longer relapse free survival period (18,19) .…”

Granulomatosis with polyangiitis and pregnancy: Anti‐neutrophil cytoplasmic antibody, placental inflammation, chorangiosis and pre‐eclampsia

“…2 Although correlation between ANCA titers and disease activity has been shown in some studies, the role of ANCAs in monitoring disease activity is contraversial. 6 The onset of the disease is usually at the fourth or fifth decades, thus pregnancy-associated GPA is rare. 3 Singh et al reported that 78 pregnancies with GPA were available in the literature.…”

Lack of elevated pre-ART elastase-ANCA levels in patients developing TB-IRIS

“…However, it still remains unclear which pre-ART factors predispose the immunesystem to trigger this excessive inflammatory response upon ART initiation. Studies on vasculitis have shown that neutrophils express auto-antigens when exposed to antigens [28]. Subsequent binding of so called anti-neutrophil cytoplasmatic antibodies, or ANCAs, leads to the activation of neutrophils and the release of reactive oxygen species, inflammatory cytokines and the corresponding tissue damage.…”

“…Taking a page out of the book of auto-immune diseases, anti-neutrophil cytoplasmic antibodies (ANCAs, a group of antibodies directed against different neutrophilic components), have been widely linked to neutrophil activation and tissue damage in small vessel vasculitides [28,29]. While anti-Myeloperoxidase (MPO) and anti-Proteinase 3 (PR3) are considered the PLOS ONE major components of the ANCA group, antibodies against other components such as bacterial permeability-increasing protein (BPI), elastase, cathepsin, lysozyme, and lactoferrin have all been described in inflammatory conditions which include; inflammatory rheumatic diseases, inflammatory bowel disease, etc.…”