Pulmonary function in patients with ANCA-associated vasculitis.

BACKGROUND AND AIM: Although pulmonary manifestations occur frequently in ANCA-associated vasculitis (AAV), empirical evidence of their impact on pulmonary function is scarce. This study analyzed pulmonary function test (PFT) data from a large cohort of patients with AVV. Results were correlated with findings from diagnostic imaging and disease activity. METHODS: Data from AAV patients with PFTs performed between 2008 and 2018 were extracted retrospectively from the database of a tertiary vasculitis center. Demographic and disease characteristics, imaging data and follow-up results were assessed and compared to PFT results. RESULTS: The final analysis encompassed 147 patients. The mean time between first PFT and follow-up was 7.0 ± 11.0 months. In Granulomatosis with Polyangiitis (GPA), forced expiratory vital capacity (FVCex, p<0.001), residual volume (RV, p<0.001) and the diffusion capacity of carbon oxide (TLCO, p=0.003) were significantly reduced compared to the reference value of 100% predicted. There was no significant difference between patients with or without pulmonary manifestations. In Microscopic Polyangiitis (MPA), reductions of FVCex (p<0.001), TLC (p=0.005), and TLCO (p=0.003) were observed. In Eosinophilic Granulomatosis with Polyangiitis (EGPA), total airway resistance (RAWtot, p=0.024) and RV (p=0.009) were significantly elevated and TLCO was reduced (p=0.014). Interstitial lung disease (ILD) is associated with a decline of FVCex (-15.7%, p=0.0028), TLC (-26.5%, p<0.001), RV (-38.9%, p=0.023) and TLCO (-29.1%, p=0.007). Significant differences were neither detected between first PFT and follow-up examination, nor between patients with active versus inactive disease. CONCLUSIONS: AAV patients presented with characteristic alterations in PFTs according to their respective pulmonary and/or airway manifestations. These results did not change over time and were independent from vasculitis activity.

Spectrum of ANCA-specificities in eosinophilic granulomatosis with polyangiitis. A retrospective multicentre study.

OBJECTIVES: To determine the spectrum of anti-neutrophil cytoplasmic antibody (ANCA) antigen-specificities in eosinophilic granulomatosis with polyangiitis (EGPA), an ANCA-associated vasculitis (AAV) entity. METHODS: We conducted a retrospective analysis of 73 EGPA patients from three German tertiary referral centres for vasculitis. In addition to in-house ANCA testing, pentraxin 3 (PTX3)- and olfactomedin 4 (OLM4)-ANCA were determined using a prototype cell-based assay for research (EUROIMMUN, Lübeck, Germany). Patient characteristics and clinical manifestations were evaluated and compared based on ANCA status. RESULTS: Myeloperoxidase (MPO)-ANCA positive patients (n=8; 11%) significantly more frequently displayed peripheral nervous system (PNS) and pulmonary involvement and less frequently heart involvement compared to MPO-ANCA negative patients. PTX3-ANCA positive patients (n=5; 6.8%) had a significantly higher prevalence of ear, nose and throat, pulmonary, gastrointestinal and PNS involvement, and a lower prevalence of renal and central nervous system involvement compared to PTX3-ANCA negative patients. Proteinase 3 (PR3)-ANCA and OLM4-ANCA were detected in 2 patients (2.7%) each with multiorgan involvement. One PR3-ANCA positive patient was also positive for bactericidal permeability increasing protein (BPI)-ANCA. CONCLUSIONS: In addition to MPO, the spectrum of ANCA antigen specificities includes various other target antigens such as PR3, BPI, PTX3, and OLM4, potentially segregating further EGPA subgroups. A lower prevalence of MPO-ANCA was detected in this study compared with other studies. OLM4 is reported as novel ANCA antigen-specificity in EGPA, and thus AAV.

Evaluation of PR3- and MPO-ANCA line and dot immunoassays in ANCA-associated vasculitis.

OBJECTIVE: This study was performed to evaluate the diagnostic accuracy of novel line and dot immunoassays for detection of MPO and PR3 ANCA. METHODS: Sera from 50 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 45 disease controls were tested by IIF and for the presence of PR3-ANCA and MPO-ANCA by four different line or dot immunoassays, as well as by a chemiluminescence immunoassay. RESULTS: The area under the curve of the receiver operating characteristic curve to discriminate AAV from controls was 0.858 (95% CI 0.785-0.931) for the IIF method. For the antigen-specific immunoassays, the area under the curve varied between 0.869 (95% CI 0.797-0.941) and 0.936 (95% 0.886-0.985). CONCLUSIONS: Our comparison of various ANCA detection methods showed a high degree of diagnostic precision for all of the PR3- and MPO-ANCA line and dot immunoassays investigated. The performance was equal to or better than the performance of IIF. These results indicate that novel line and dot immunoassays can serve as a first-line test method in patients with the suspected diagnosis of AAV.

Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

OBJECTIVES: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. METHODS: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. RESULTS: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. CONCLUSION: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Two Immunocompromised Patients With Diffuse Alveolar Hemorrhage as a Complication of Severe Coronavirus Disease 2019.

Diffuse alveolar hemorrhage (DAH) is a severe and potentially life-threatening disease manifestation. In addition to autoimmune diseases such as antineutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane syndrome, pulmonary viral infections are known to be culprits of DAH. Health-care providers worldwide in the coronavirus disease 2019 pandemic have been confronted with an unprecedented number of viral lung infections, with great variance in symptoms and severity. Hemoptysis, the key symptom of DAH, is a rare complication. We present two cases of immunocompromised patients with rapidly developing hypoxemic respiratory failure and evidence of DAH in the context of severe acute respiratory syndrome coronavirus 2 infection.

Anti-neutrophil cytoplasm antibodies (ANCA): Recent methodological advances-Lead to new consensus recommendations for ANCA detection.

The current practice for detection of anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO) has been screening by indirect immunofluorescence (IIF) followed by an antigen specific tests for PR3- and MPO-ANCA. However, ANCA diagnostics have undergone many technical developments that have affected the 1999 international consensus recommendations, and lead to a revision of the existing ANCA detection strategy. Recent European multicentre studies have compared the diagnostic performance of various ANCA detection methods and demonstrated that PR3- and MPO-ANCA immunoassays yielded the highest diagnostic accuracy. New guidelines for ANCA testing have been developed based on these data. According to the revised 2017 international consensus recommendations, testing for ANCA in small vessel vasculitis can be done by PR3- and MPO-ANCA immunoassays, without the categorical need for IIF. Thus, IIF can be discarded completely, or can be used as confirmation assays instead a screening test. Clearly, though, the new testing strategy for ANCA in vasculitis must identify the ANCA target antigen, as PR3- and MPO-ANCA serotype correlate well with disease expression. Furthermore, recent studies have shown that AAV can be classified based on ANCA serotype, since PR3- and MPO-ANCA- diseases are strongly associated with distinguishable genetic alleles, different clinical and histological features. ANCA presence and the antigen specificity also may have important value as a prognostic factor and may serve as a guide for immunosuppressive therapy. In the current review, we summarize the novelties in ANCA testing, present the 2017 revised international consensus on ANCA testing in vasculitis, evaluate the diagnostic significance of ANCA, and discuss the role of ANCA serotypes in the diagnostic work-up of patients with AAV.