The endothelium is crucially important for the delivery of oxygen and nutrients throughout the body under homeostatic conditions. However, it also contributes to pathology, including the initiation and perpetuation of inflammation. Understanding the function of endothelial cells (ECs) in inflammatory diseases and molecular mechanisms involved may lead to novel approaches to dampen inflammation and restore homeostasis. In this article, we discuss the various functions of ECs in inflammation with a focus on pathological angiogenesis, attraction of immune cells, antigen presentation, immunoregulatory properties and endothelial-to-mesenchymal transition (EndMT). We also review the current literature on approaches to target these processes in ECs to modulate immune responses and advance anti-inflammatory therapies.
ObjectivesAn important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA.MethodsWe included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1–2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers.ResultsThe median qPCR score was higher in active GPA (21.4; IQR 12.1–29.6) than in remission/LDA (3.3; IQR 1.6–5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05).ConclusionsThe IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1806-6) contains supplementary material, which is available to authorized users.
ObjectivesANCA-vasculitis (AAV) patients frequently suffer from relapses and risk subsequent organ damage. There is much debate on the value of serial ANCA level evaluation to monitor disease activity. We aimed to evaluate the association between ANCA rises and disease relapses at (I) moment of the rise, (II) within 6 months or (III) within a year from the rise.Methods3 databases (MEDLINE, EMBASE, COCHRANE) were searched from 1993 through September 2021. We included studies that reported relapse incidence within 12 months after an ANCA rise measured by antigen-specific immunoassays in peripheral blood of AAV patients in remission. Quality assessment was performed using QUADAS-2. Finally, a meta-analysis was carried out to estimate average OR using a random effects model.ResultsTwenty unique studies were included. The methodological quality was limited due to risk of selection bias. An ANCA rise often preceded a disease relapse within 6 months (OR 3.65, 95% CI 1.66–8.03) and less often within 12 months (OR 2.88, 95% CI 1.21–6.88), while it was not indicative of a concurrent relapse (OR 0.13, 95% CI 0.03–0.53). Once a relapse is diagnosed, ANCA is significantly more often present than not (OR 10.80, 95% CI 3.82–30.55). As expected based on clinical, technical and methodological variability between studies, there was substantial heterogeneity across studies in all analyses (I2 = 70–87%).ConclusionIn previously ANCA-positive patients, the ANCA test is often positive upon clinical suspicion of a disease relapse. Patients with a rise in ANCA are at risk of encountering disease relapses in the upcoming 6 or 12 months.
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