ANCA-associated Vasculitis Patients Research Articles

Gut microbiota differences between psoriatic arthritis and other undifferentiated arthritis: A pilot study.

Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients' than in PSA patients' stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group.Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation.The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.

Relationship Between Gender and 1-Year Mortality in ANCA-Associated Vasculitis Patients: A Single-Center Retrospective Analysis and Meta-Analysis.

ObjectiveThe relationship between gender and short-term prognosis of patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is unclear, hence single-center retrospective analysis and meta-analysis were conducted to determine the relationship.MethodsInitially treated patients with AAV were retrospectively enrolled. Data of clinical manifestation, laboratory indicators, Birmingham vasculitis activity score (BVAS), therapeutic treatments, and the patients' situations within 1 year were recorded. First, we compared the basic characteristics between male and female patients. Second, the risk factors associated with a 1-year mortality rate of patients with AAV were evaluated. Finally, a meta-analysis was performed to explore the effect of gender on 1-year mortality in patients with AAV.ResultsThe study involved 84 patients with AAV, including 33 female and 51 male participants. In total, 14 people died (12 males and 2 females) and 70 survived in the 1st year. Statistical differences were noted in the age of onset, the course of the disease, WBC, HB, N, ESR, CRP, BUN, ALT and ALB, BVAS, and 1-year mortality rate between male and female participants. In male patients, elevated Scr, NLR, PLT, and RDW-CV were associated with poor AAV (P < 0.05) prognosis. The meta-analysis verified that male gender was an independent risk factor for the 1-year mortality of patients with AAV(OR = 1.54).ConclusionSignificant sex-specific differences were found in patients with AAV. Male patients contributed to 1.54-fold of 1-year mortality risk in patients with AAV by meta-analysis. More attention should be paid to the mortality risk of male patients with AAV in the early stage.

Clinical significance of HEp-2 cell cytoplasmic patterns in anti-neutrophil cytoplasmic antibody associated vasculitis.

The study was to investigate the clinical characteristics and significance of antinuclear antibody (ANA) cytoplasmic patterns in ANCA-associated vasculitis (AAV) from Southwest China.A retrospective study including 232 AAV patients from Peoples Hospital of Deyang City was performed. These included 115 patients with ANA cytoplasmic pattern as observation group and 117 patients without ANA cytoplasmic pattern as control group.Chest involvement (60.00 vs 46.15, P = .035), cardiovascular involvement (5.21 vs 29.91, P < .001), and renal involvement (37.39 vs 77.78, P = .001) were different between groups.Total protein (69.55 vs 64.01, P < .001), triglyceride (1.41 vs 1.18, P = .023), mean cell volume (89.76 vs 87.59, P = .040), and estimated glomerular filtration rate (76.67 vs 50.87, P = .035) were higher in ANA cytoplasmic patterns group. Creatinine (73.00 vs 117.50, P = .011), white blood cell (6.93 vs 8.86, P = .001), platelet (196.0 vs 239.0, P = .017), anti-myeloperoxidase (2.44 vs 3.42, P = .042), and anti-proteinase 3 (1.00 vs 4.93, P = .007) were lower in this group. In multivariate analysis, creatinine (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.06–1.38), triglyceride (OR = 1.97, 95% CI: 1.10–3.48), and anti-myeloperoxidase (OR = 1.64, 95% CI: 1.37–1.95) were independent risk factors of AAV renal involvement. Total protein (OR = .95, 95% CI: 0.91–0.99) was an independent protective factor of AAV renal involvement. Chi-square test showed that speckled pattern was different among anti-neutrophil cytoplasmic antibody patterns (χ2 = 18.526, P < .001).In summary, HEp-2 cell cytoplasmic patterns have certain clinical significance in AAV, which is a new exploration of the clinical value of ANA.

Interstitial lung disease in ANCA-associated vasculitis: associated factors, radiographic features and mortality.

To evaluate the prevalence, clinical and radiographic features, and long-term outcomes of interstitial lung disease (ILD) in a United States-based ANCA-associated vasculitis (AAV) cohort. In this retrospective cohort study, we identified cases of ILD within the 2002-2019 Mass General Brigham AAV Cohort, a consecutive inception cohort of PR3- or MPO-ANCA+ AAV patients. ILD diagnosis and classification as fibrotic or non-fibrotic were confirmed by review of available chest imaging by two board-certified radiologists. Cox proportional hazard models, with age as the time scale, were used to estimate the association of AAV-ILD with all-cause mortality. Of 684 patients in the MGB AAV Cohort, 91 (13%) had ILD which preceded the diagnosis of AAV by a mean of 2.2 years. AAV-ILD patients were older (67 vs 60 years, P < 0.001) than patients without ILD but the distribution of sex and race was similar. AAV-ILD patients were more often MPO-ANCA+ (93% vs 65%, P < 0.001); among MPO-ANCA+ patients (n = 470), 85 (18%) had ILD. The majority of ILD was fibrotic (76%) and UIP was the most common ILD pattern (42%). The baseline forced vital capacity (FVC) % predicted among ILD patients was 81 ± 20%. Fibrotic AAV-ILD was associated with a 58% higher risk of death (aHR 1.58, 95% CI 1.06, 2.37) compared with AAV patients without ILD. ILD is a frequent complication of AAV, especially MPO-ANCA+ AAV, often preceding recognition of AAV. Fibrotic AAV-ILD is associated with a higher risk of death than AAV without ILD.

Bronchiectasis in patients with antineutrophil cytoplasmic antibody-associated vasculitis: a case control study on clinical features and prognosis

Background : Bronchiectasis was reported in 2%-40% of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), but there were no studies on the prevalence, risk factors and impact of AAV-associated bronchiectasis in Chinese patients. Research design and methods AAV patients were retrospectively enrolled. The clinical, laboratory and imaging features and the prognosis were analyzed and compared between those with and without bronchiectasis. Results Bronchiectasis was present in 48/212 (22.6%) of our AAV patients, among whom 41 were confirmed in 210 patients (19.5%, 41/210) who received chest HRCT at the initial diagnosis of AAV. There were more women and fewer smokers in those with bronchiectasis as compared to those without. Cases with positive anti-MPO were more likely to have bronchiectasis (26.2%), and those with bronchiectasis were more likely to be anti-MPO positive (93.8%). Patients who had a diagnosis of bronchiectasis before AAV were more likely to have nervous system involvement, while patients without bronchiectasis had higher 24h proteinuria. The presence of bronchiectasis showed no significant effect on the 1, 3, 5-year survival. Conclusions Nearly 20% of patients showed bronchiectasis on chest HRCT at the initial diagnosis of AAV, and positivity of anti-MPO was associated with bronchiectasis in a Chinese cohort of AAV patients.

AB0606 Health-related quality of life in patients with rituximab-induced remission of ANCA-associated vasculitis: registry-based cohort studies

BackgroundSurvival rate in ANCA-associated vasculitis (AAV) has significantly improved due to anti-B cell therapy with rituximab (RTX). The main issue now appears to be the management of comorbidities and the improvement of quality of life.ObjectivesBased on a prospective analysis of the single centre registry of AAV patients (pts) treated with RTX, to study the impact of sustained remission on health-related quality of life using Short-Form 36 (SF-36).MethodsHealth-related quality of life was assessed in 70 AAV pts: 35 (50%) with granulomatosis with polyangiitis (GPA), 24 (34.3%) - microscopic polyangiitis (MPA) and 11 (15,7%) - eosinophilic granulomatosis with polyangiitis (EGPA). The mean age was 49,7 ± 15,7 years, 53% women. The median total dose of RTX was 4.3± 2,5 g. As a rule, a reduced dose of RTX 500 mg was used for repeated courses. Mean duration of RTX therapy 46.8 ± 29.4 months. Remission of AAV was defined as a Birmingham Vasculitis Activity Score = 0 regardless of prednisone treatment or dosage. All pts were in remission.ResultsIn 70 patients the average indicators of physical functioning: MPA 62.5 (47.5, 78.8), GPA 75 (55, 92.5), EGPA 60 (45, 77.5); social functioning: MPA 25 (0, 56.3), GPA 50 (25, 100), EGPA 50 (12.5, 62.5), physical health component: MPA 41.6 (31.5, 44.8), GPA 43.7 (36.7, 52.5), EGPA 38.7 (33.8, 45). There were no significant differences between men and women within the GPA, MPA, and EGPA groups. There were also no differences between different age groups. When comparing the EGPA group with GPA or MPA, no significant differences were found. At the same time, in patients with MPA, the indicators of physical functioning (p=0.015, w= 3.92) and the physical component of health (p=0.012, w 4.026) were significantly lower than in patients with GPA.ConclusionRTX maintenance allows to achieve a good quality of life in AAV pts. SF-36 summary measures were significantly higher in GPA pts compared with MPA. Further research is required to analyze the effect of AAV phenotype and complications on health-related quality of life.

Cutaneous manifestations of ANCA-associated vasculitis: a retrospective review of 211 cases with emphasis on clinicopathologic correlation and ANCA status.

ANCA-associated vasculitis (AAV) may present a wide array of dermatological manifestations. Patients may remain ANCA negative, rendering diagnosis challenging for dermatologists if they depend heavily on ANCA testing to either confirm or rule out AAV. To compare clinical and histopathological features of AAV patients with skin lesions who are ANCA positive versus those who are ANCA negative. Retrospective review of medical charts to identify patients diagnosed with AAV by clinical and pathologic criteria who also had cutaneous manifestations. Search revealed that 211 out of 932 (23%) patients had cutaneous manifestations. Of those, 40/211 (20%) patients had persistently ANCA-negative serology. Eosinophilic granulomatosis with polyangiitis (EGPA) comprised the largest cohort. Palpable purpura was the most prominent clinical feature. The most common histopathological feature was leukocytoclastic vasculitis (LCV) in 19 (29%) specimens, extravascular granuloma in 14 (22%), followed by perivascular infiltrate in 12 (18%), with eosinophils in nine. In the ANCA-negative subgroup, perivascular infiltrate was more common followed by LCV but without statistically significant difference. Diagnosis of AAV should not be based on ANCA testing alone since a considerable number of patients with cutaneous lesions may be ANCA negative. The clinical or histopathologic findings of skin lesions in this study group did not vary based on ANCA status.

Exploring the educational needs of patients with systemic vasculitis using the educational needs assessment tool.

ObjectivesKnowledge and health literacy enable patients to monitor symptoms and disease impact. Educational needs have previously been explored in rheumatology, but scarcely for patients with ANCA-associated vasculitis (AAV). The aim of the study was to assess the educational needs among patients with AAV using the educational needs assessment tool (ENAT).MethodsThis was a cross-sectional observational study including adults with AAV. Educational needs were captured by ENAT. Total ENAT (0–117 points, with higher numbers indicating higher educational need) and the seven domains (managing pain, movement, feelings, disease process, treatment, self-management and support systems) were explored regarding sex, age, education, diagnosis, disease duration and disease activity. To compare domains, a percentage response (0–100%) was calculated.ResultsOne hundred and seventy-eight individuals (50% men; 34% with disease duration ≤2 years) were included. The total ENAT mean was 66.5 (s.d. 26.6; 57%), with domains as follows: disease process, 78%; self-management, 69%; treatments, 64%; feelings, 56%; managing pain, 48%; support systems, 47%; and movement, 41%. Higher educational needs were found among women in the domains movement, feelings and disease process and in total ENAT (all P < 0.04) compared with men. Higher educational needs were also seen in patients with disease duration ≤2 years regarding disease process, self-management and support systems and in total ENAT compared with patients with longer disease duration (all P < 0.03).ConclusionThis study revealed great educational needs among AAV patients. Some groups expressed higher needs (women and those with shorter disease duration). Increased education for patients with AAV might lead to improved self-care and treatment adherence.

Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients.

ObjectivesDiagnosing patients with ANCA-associated vasculitis (AAV) can be challenging owing to its rarity and complexity. Diagnostic delay can have severe consequences, such as chronic organ damage or even death. Given that few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the diagnostic phase.MethodsThis retrospective, observational study of electronic medical records data in hospitals focused on diagnostic procedures during the first assessment until diagnosis.ResultsWe included 230 AAV patients from nine hospitals. First assessments were mainly performed by a specialist in internal medicine (52%), pulmonology (14%), ENT (13%) or rheumatology (10%). The overall median time to diagnosis was 13 [interquartile range: 2–49] days, and in patients primarily examined by a specialist in internal medicine it was 6 [1–25] days, rheumatology 14 [4–45] days, pulmonology 15 [5–70] days and ENT 57 [16–176] days (P = 0.004). Twenty-two of 31 (71%) patients primarily assessed by a specialist in ENT had non-generalized disease, of whom 14 (64%) had ENT-limited activity. Two hundred and nineteen biopsies were performed in 187 patients (81%). Histopathological support for AAV was observed in 86% of kidney biopsies, 64% of lung biopsies and 34% of ENT biopsies.ConclusionIn The Netherlands, AAV is diagnosed and managed predominantly by internal medicine specialists. Diagnostic delay was associated with non-generalized disease and ENT involvement at presentation. Additionally, ENT biopsies had a low diagnostic yield, in contrast to kidney and lung biopsies. Awareness of this should lead to more frequent consideration of AAV and early referral for a multidisciplinary approach when AAV is suspected.

Rituximab treatment in ANCA-associated vasculitis patients: outcomes of a real-life experience from an observational cohort.

Rituximab is a first-line therapy in patients with anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Among previous studies evaluating its efficacy, the Hispanic/Latino population has been underrepresented. This study aimed to assess the outcomes of AAV patients treated with rituximab in a tertiary care center in Mexico. This is a retrospective cohort study including patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or renal-limited vasculitis (RLV), who received at least one dose of rituximab (induction or maintenance therapy) from January 2014 to October 2020. Demographic, clinical, serological, histopathological, and treatment-related variables were retrieved. Outcomes were the rate of remission at 6 months during induction and the rate of relapses during maintenance. Damage, serious infections, and death were assessed. Differences between patients with and without remission were analyzed. Forty-two patients received rituximab, 34 of them as induction to remission. Twenty-two patients (65%) achieved remission after 6 months. Patients who achieved remission were younger than those who did not (50 vs. 60 years, p = 0.03). During induction, severe infections, most frequently pneumonia, occurred in 9 (26%), and one patient died. Twenty-four patients received rituximab as maintenance; of them, 23 (96%) achieved complete response, and 8 (33%) experienced relapses (median follow-up time 19 months). During maintenance, severe infections (pneumonia) occurred in 5 patients (21%), and 3 of them (13%) died. In this observational cohort study, the outcomes were similar to the ones reported in other populations, whereas severe infections were frequent and associated with mortality. Key Points• In this study, the outcomes of 42 Mexican patients with ANCA-associated vasculitis treated with rituximab were assessed in a real-life setting.• At 6 months, 65% of the patients achieved remission with rituximab, especially those younger than 50 years of age.• During maintenance therapy with rituximab, 96% of the patients achieved complete response, and 33% experienced relapses.• Severe infections, mostly pneumonia, occurred in 26% of patients during induction and 21% of patients during maintenance therapy with rituximab.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10067-022-06192-1.

FC061: Renal Function is a Major Determinant of B-Cell Repopulation Following Rituximab Induction in Anca-Associated Vasculitis

Abstract BACKGROUND AND AIMS Rituximab is increasingly used to induce and maintain remission in ANCA-associated vasculitis (AAV). However, it remains unclear what the optimal dosing regimen is, especially in the setting of maintenance. Clinical trials have shown that vasculitis flares are unlikely as long as B-cell depletion in peripheral blood is sustained, with some evidence supporting a rituximab redosing strategy guided by B-cell-count monitoring. A better understanding of B-cell kinetics following rituximab treatment can facilitate personalized treatment approaches. This study aims to (1) describe B-cell repopulation in AAV patients treated with rituximab induction, and (2) identify clinical features predictive of B-cell repopulation. METHOD This is a single-centre, retrospective study, including AAV patients on no baseline immunosuppression who were treated with rituximab induction between December 2009 and March 2018 in the Nephrology Unit of Spedali Civili, Brescia. Only patients with available longitudinal B-cell monitoring for at least 6 months following rituximab were considered. B-cell counts were determined as CD19 + cells in peripheral blood using flow cytometry (Beckman Coulter Navios©). B-cell repopulation following rituximab was defined as CD19 + cell count &amp;gt;10 cells/μL, with a documented CD19 + count ≤ 10 cells/μL within the preceding year. For each patient, CD19 + cell counts were followed up to the earliest event among the following: (1) B-cell repopulation, (2) retreatment with rituximab or other induction agents, or (3) most recent observation available. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Flares were defined as active disease retreated with rituximab or cyclophosphamide and classified as major if one or more major items of the BVAS score v3 were present. Predictors of time to B-cell repopulation were assessed using uni- and multivariate analysis with log-rank test and Cox proportional hazards regression, respectively. RESULTS The study cohort included 64 patients. The main clinical characteristics are summarized in Table 1. During a median follow-up of 33.4 months (range 7.5–101.7 months), B-cell repopulation was observed in 36 patients (56.2%). Median time from rituximab induction to B-cell repopulation was 39.8 months [95% confidence interval (95% CI) 33.8–69.7]. Gender, ANCA subtype, rituximab dose, steroid pulses, plasma exchange and methotrexate/azathioprine maintenance were not significantly associated with time to B-cell repopulation. In contrast, B-cell repopulation was significantly slower in patients who were older (median time to repopulation 51.6 months in patients ≥ mean age of 66.8 years old versus 33.9 months in &amp;lt; mean age; P = 0.044), who had microscopic polyangiitis (median 51.6 months), as opposed to granulomatosis with polyangiitis (median 33.9 months; P = 0.012) and who had lower eGFR at the time of rituximab (69.7 months in eGFR &amp;lt; median of 18.3 mL/min/1.73 m2 versus 28.4 months in eGFR ≥ median; P = 0.001, Figure 1). Of these three predictors, only eGFR remained significantly associated with time to B-cell repopulation in a multivariate Cox regression model (hazard ratio for B-cell repopulation in eGFR ≥ median: 2.74, 95% CI 1.31–5.72). During sustained B-cell depletion, six vasculitis flares were observed, of which one was major (rise in creatinine &amp;gt; 30%) and the rest were minor (n = 4 worsening of urine abnormalities, n = 1 retro-orbital pain). CONCLUSION A substantial proportion of AAV patients treated with a single course of rituximab shows sustained B-cell depletion. Renal function emerged as the main independent predictor of B-cell repopulation, with delayed B-cell repopulation in people with kidney impairment. Only one major vasculitis flare was observed during sustained B-cell depletion. These data support the idea that longitudinal monitoring of B-cell counts can be a useful biomarker to guide rituximab dosing for maintenance in AAV, especially in patients with kidney impairment.

FC057: Incidence of Infections in the Avacopan Group Versus Prednisone Group in Anca-Associated Vasculitis, Results from the Phase 3 Advocate Study

Abstract BACKGROUND AND AIMS Standard therapy for ANCA-associated vasculitis (AAV) includes glucocorticoids (GC), which are associated with increased infections. Avacopan is an orally administered selective inhibitor of the C5a receptor recently approved for treatment of AAV. The phase 3 ADVOCATE study tested daily avacopan as a substitute for a standard, scheduled, daily oral GC tapered regimen (all with standard background therapy), resulting in a 63% mean reduction in overall GC load for the avacopan group. At week 26, the avacopan group achieved a comparable remission rate to prednisone (72.3% versus 70.1%) and superior sustained remission at Week 52 (65.7% versus 54.9%; one-sided P = 0.0066) (1). The present analysis compared infections in avacopan and prednisone groups in the ADVOCATE trial. METHOD ADVOCATE, a phase 3, randomized, double-blind, controlled trial in 330 patients, evaluated the efficacy and safety of avacopan. AAV patients (new onset or relapsing disease) were randomized to receive avacopan 30 mg twice daily, or a standard 20-week oral prednisone taper, plus matching placebos. Both groups had background therapy of either cyclophosphamide (followed by azathioprine) or rituximab, and additional GC exposure from premedication for rituximab, from taper of pre-randomization GC, and as required per investigator judgment. Patients were on blinded study drug for 52 weeks. Infections occurring from first dose of blinded study drug through day 56 after last dose were analyzed. RESULTS Total mean GC use during the first 26 weeks of the study was 1073 mg with avacopan and 3193 mg with prednisone groups, and in the last 26 weeks, 296 and 489 mg, respectively. Infections were higher in the prednisone group than with avacopan: 291 events (prednisone) versus 233 (avacopan), with a 75.6% incidence (124/164) with prednisone versus 68.1% (113/166) with avacopan (Table 1). During the prednisone taper period (first 20 weeks), infection incidence was 54.9% in prednisone group versus 49.4% for avacopan, and after the first 20 weeks 52.4% in prednisone group versus 44.0% avacopan. Fewer patients in the avacopan group experienced serious AEs of infection (13.3%/25 events) versus prednisone group (15.2%/31 events); also serious opportunistic infections (3.6% versus 6.7%), life-threatening AEs of infection (0.6% versus 1.2%), and infections resulting in death (0.6% versus 1.2%) were fewer with avacopan (Table 1). No Neisseria meningitidis infections occurred in any patient in the trial. CONCLUSION In the ADVOCATE trial, the mean dose of GCs from all sources was 63% lower in the avacopan group than the prednisone group (1349 versus 3655 total mg, respectively). The avacopan group had a numerically lower incidence of infections, including serious, life-threatening, fatal and serious opportunistic infections compared with the prednisone group.

FC075: Role of Factor H and its Related Proteins (FHR-1, FHR-2 FHR-5) in ANCA-Associated Vasculitis: A Genetic and Longitudinal Serological Study

Abstract BACKGROUND AND AIMS The complement system was not initially thought to be associated with the development of ANCA-associated vasculitis (AAV). Convincing evidence from animal models and clinical observations indicates, however, that activation of the complement system, the alternative pathway (ACP) in particular, is pivotal for the development of AAV. Recently, a phase 3 clinical trial has shown that C5a receptor inhibition with avacopan was effective in replacing high dose glucocorticoids in AAV patients treated with rituximab or cyclophosphamide during induction treatment. We hypothesized that in AAV, a disorder in regulatory factors of ACP or in its related proteins (FHR-1, FHR-2, FHR-5) could be present, similar to other diseases in which its dysregulation have been shown. Method We measured longitudinal levels of alternative complements factors (FH, FB, properdin, FHR-1, FHR-2, FHR-5) and performed a genetic study for these factors in three cohorts: active renal ANCA vasculitis (active AAV, n = 54), inactive ANCA vasculitis (remission, n = 48) and in a control cohort of healthy individuals (n = 99). RESULTS ANCA serology was positive in all patients; 83.3% showed activity against MPO, whereas activity against PR3 was identified in 16.7% of patients. Median BVAS at the onset was 15 (IQR 14–19). Extrarenal involvement was present in 46.3% of participants. Haplotype CFH-H6 and the allele CFB32R are significantly associated with increased risk to develop AAV [OR 3.32; 95% confidence interval (95% CI) 1.39–7.89; P = 0.008 and OR 1.71, 95% CI 1.11–2.54; P = 0.008, respectively]. The allele frequency of ΔCFHR3/1 was significantly decreased in patients with severe AAV (T3, BVAS &amp;gt; 16) compared with patients with a lower BVAS score (T1-T2 ≤ 15). Circulating levels of regulatory factors (FH, FB, properdin) were significantly lower in patients with active disease compared to samples in remission, and FHR1 (FH competitor) levels were higher. C3 levels increased over time, while sC5b-9 decreased after initiating the immunosuppressive treatment, with the biggest change observed after the first month of treatment. After 12 months of follow-up, FHR-1 levels decreased in responder patients and did not decrease in nonresponders. CONCLUSION This is the first study to associate the presence of certain alleles of regulatory factors of the alternative complement pathway (Factor H and Factor B) with an increased risk of developing ANCA-associated vasculitis. Likewise, the absence of the ΔCHR3-CFHR1 deletion was associated with more severe forms of the disease. We could conclude that ACP is not a simple additional factor in the inflammatory loop in AAV and, like in other glomerular diseases related to ACP, dysregulation of FH and its regulatory proteins play an essential role in its development.

MO223: Contribution of Interstitial CD138 + Plasma Cells on the Renal Outcome in Patients with Anca-Associated Vasculitis

Abstract BACKGROUND AND AIMS Plasma cells (PC) are the most differentiated antibody and cytokine-producing B lineage cells and are thought to contribute to the perpetuation of inflammation in patients with ANCA-associated vasculitis (AAV). Agents targeting PCs are of interest in AAV, however, little is known about the role of interstitial CD138 + PCs in these patients. In this study, we aim to demonstrate the impact of this cell population in the prediction of renal outcomes in patients with AAV. METHOD Forty AAV patients with glomerulonephritis, diagnosed between 2014 and 2018 at the Division of Nephrology of the Medical University of Graz were included and followed for 36 months. Histological assessments using the kidney allograft Banff classification were performed to describe the tubulointerstitial (TI) damages. Immunohistochemistry analysis was performed in 29 patients to assess the renal interstitial CD138 + cell expression. More than ten CD138 + cells per high power field were stated as high expression (excluding CD138 staining of renal tubular epithelial cells). Changes in kidney function, the incidence of renal relapses (RR), and end-stage renal disease (ESRD) were analyzed. RESULTS In the kidney biopsies, N = 21 (72%) patients had a high expression of CD138 + plasma cells. No significant difference was observed in PR3 and MPO serotypes in the group of patients with high CD138 + cell expression (43% versus 57%, P = .793). In addition, no significant difference was seen in the changes in kidney function and the incidence of RR or ESRD between the groups with high and low expression of CD138 + cells during the follow-up period. However, patients with more severe TI damage had more severe proteinuria {urinary albumin/creatinine ratio: 51 [interquartile range (IQR) 42–123] versus 360 (IQR 202–1112) mg/g Creatinine; P = .016} at 3-year follow-up, and tended to have a higher rate of RR and ESRD [i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258 and i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258, respectively]. CONCLUSION Our data indicate a significant proportion of CD138 + PCs in kidney specimens of patients with AAV. Despite the lack of association between this cell population and our cohort’s renal outcome, these results provide additional insights on the renal B-cell clusters in patients with AAV. In addition, our findings go along with already existing data on the association between extended TI damage and worse renal outcome.

FC058: Long-Term Renal Survival of Anca-Associated Vasculitis Patients Included in the Euvas Randomized Clinical Trials

Abstract BACKGROUND AND AIMS Kidney involvement is common in ANCA-associated vasculitis (AAV) and prognosis is largely determined by the severity of the kidney damage at diagnosis and by the response to treatment. Rapidly progressive glomerulonephritis is the most common severe clinical manifestation of AAV. Current therapy with immunosuppressive and glucocorticoid treatment plays a crucial role to rescue kidney function, but the rate of patients reaching end-stage renal disease (ESRD) remains high. The aim of the study is to determine the renal prognosis and predictive factors of patients included in EUVAS randomized controlled trials (RCTs) by the European Vasculitis Society from 1995 to 2012: MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC. METHOD Questionnaires were sent to the principal investigators of the original RCTs and 490 were returned (70% of the potential patients). The dataset comprised 848 patients, all newly diagnosed with AAV, well characterized at inclusion in the trials, as was the type and duration of induction therapy. RESULTS Median follow-up time for the entire cohort was 8 years [interquartile range (IQR): 2.9–13.6]. 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (47%) microscopic polyangiitis (MPA). Mean age at diagnosis was 57.5 ± 14.2 years. Renal involvement was detected in 644 (76%) patients at diagnosis, with a median eGFR of 42.1 (IQR: 16.2–88.6) mL/min/1.73 m2. At baseline, 199 patients had an eGFR &amp;lt;15 mL/min/1.73 m2 and another 144 an eGFR 15–30 mL/min/1.73 m2. A totla of 107 patients needed dialysis at initial presentation. However, 37 out of the 107 recovered renal function later and 11 patients were temporarily dialysis independent but needed subsequent dialysis. A total of 105 started renal replacement therapy (RRT) after the end of the initial RCTs. A total of 175 patients required RRT during long-term follow-up. A total of 35 patients received a kidney transplant and they showed better survival than patients receiving other modalities of RRT (LR: 42.2; P-value &amp;lt; 0.001) (Figure 1). Among patients with ESRD, 67 (38%) had GPA and 108 (62%) had MPA-RLV. Median baseline eGFR was 13.2 (IQR: 7.3–26) mL/min/1.73 m2. Patients with ESRD were older at entry (62.3 ± 13.4 versus 57 ± 14.1 years) (P-value &amp;lt; 0.001), had baseline lower hemoglobin level (9.2 ± 1.8 versus 10.3 ± 2 g/dL) (P-value &amp;lt; 0.001) and lower baseline platelets count (366 ± 182 versus 406 ± 164 *109/L) (P-value: 0.006). The cumulative incidence of ESRD at 5 and 10 years was 16.7% and 22.5%, respectively. A total of 118 deaths were found among the patients who developed ESRD (67.4%). Those with ESRD had reduced survival when compared with those with preserved kidney function (log-rank: 97.2; P-value &amp;lt; 0.001) (HR: 2.8; P-value &amp;lt; 0.001).The most frequent causes of death were infection (29.7%) followed by cardiovascular disease (16.9%) and malignancy (5.9%). GPA patients who had ESRD had better prognosis compared to MPA-RLV (HR: 5.4; P-value: 0.02) (Figure 2). When compared to a matched general population (matched by age, sex and country), even those patients with AAV and mild renal impairment (eGFR &amp;gt; 30 mL/min/1.73 m2) had a worse prognosis. CONCLUSION Our findings, which were derived from a large number of patients with AAV enrolled in EUVAS’ RCTs over the past 25 years, estimate the 5- and 10-year cumulative incidence of ESRD to 16.7% and 22.5%, respectively. ESRD is tightly associated with decreased patient survival.

Clinical Features and Prognosis in ANCA Associated Vasculitis Patients with Acute Kidney Injury

Renal involvement in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) often presents as acute kidney injury (AKI), which is closely related to the prognosis of critically ill patients. Nevertheless, there are few researches on the subgroup of AVV patients with AKI. The study aimed to explore clinical features and prognosis in AAV patients with AKI. A retrospective analysis of AAV patients was conducted. The enrolled patients were grouped according to whether AKI on admission occurred or not. Demographic, clinical data and follow-up records were gathered from medical histories. Survival rates of AAV patients with AKI and risk factors of all AAV patients were studied. (1) In the AKI group, the levels of hemoglobin, evaluated glomerular filtration rate (eGFR), serum albumin and complement 3 were significantly lower (P<0.05); the proportions of microscopic polyangiitis (MPA) and levels of serum creatinine (SCr) on admission, red blood cell (RBC) counts in urine, 24-hour urine protein excretion (UPE) and Birmingham Vasculitis Activity Score (BVAS) were significantly higher (P<0.05). There was a significantly lower incidence of otorhinolaryngologic involvement in the AKI group (P<0.05). (2) There were significantly lower survival rates and renal survival rates in the AKI group (P<0.05). (3) Higher creatinine and AKI were risk factors for poor prognosis in AAV patients. AAV patients with AKI have more severe kidney damage, higher disease activity and worse prognosis. More attention should be paid to AAV patients with AKI for both remission induction and infection prevention.

Prognostic Value of Hematological Parameters in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Objective: Hematological parameters including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), and monocyte–lymphocyte ratio (MLR) have been demonstrated as new predictors of prognosis and activity in various diseases. In this study, we aimed to investigate the associations of NLR, PLR and MLR with disease severity and prognosis in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). &#x0D; Materials and Methods: Medical records of 92 AAV patients were investigated retrospectively. The clinical and laboratory data, and disease outcomes were recorded. The patients having five factor score (FFS) ≥ 2 were categorized as severe disease.&#x0D; Results: 92 patients with a median age of 60 years were included. Patients with NLR≥4.8 (RR 1.83), PLR≥151.8 (RR 2.02) and MLR≥0.38 (RR 1.85) had higher risk of severe disease. In correlation analysis, NLR, PLR and MLR were positively correlated with C reactive protein and erythrocyte sedimentation rate (ESR). NLR, PLR and MLR were associated with remission. &#x0D; Conclusion: Only the patients with high PLR had higher relapse rate. MLR was also correlated with development of end-stage renal disease (ESRD). Renal involvement was more frequent in patients with high levels of NLR, PLR and MLR. &#x0D; Conclusions: We showed that NLR, PLR and MLR at diagnosis were associated with the severity and prognosis of AAV. This is the first study, showing the correlation of MLR with disease severity and ESRD in patients with AAV.

The Association of Serum Anti-Lysosomal-Associated Membrane Protein-2 Antibody with Vasculitis Combined with Hypertension.

The aim of this study was to explore the association of serum anti-lysosomal-associated membrane protein-2 (anti-LAMP-2) antibody with vasculitis combined with hypertension (VAS-HTN). A total of 51 VAS-HTN patients, 46 essential hypertension (EH) patients, and 46 healthy controls (HC) were included in the study. Serum anti-LAMP-2 antibody levels are increased in VAS-HTN patients as compared with EH and HC (all P < 0.05). Serum anti-LAMP-2 antibody levels were significantly higher in active stage patients than those in non-active stage patients and HC (all P < 0.05). The correlation analysis showed a significant positive correlation between serum anti-LAMP-2 antibody levels and the Birmingham Vasculitis Activity Score (BVAS) and hypersensitive C-reactive protein (Hs-CRP) (all P < 0.05). Among the subsets of VAS-HTN, the levels of serum anti-LAMP-2 antibody were remarkably higher in all VAS-HTN subsets compared with HC (all P < 0.05). More interestingly, the levels of serum anti-LAMP-2 antibody were remarkably increased in polyarteritis nodosa (PAN) patients compared with ANCA-associated vasculitis and Takayasu arteritis patients (all P < 0.05). In addition, there was a significant positive correlation between serum anti-LAMP-2 antibody levels and BAVS and Hs-CRP in PAN patients (all P < 0.05). Multivariate logistic regression analysis showed that the anti-LAMP-2 antibody was independently associated with VAS-HTN. The levels of serum anti-LAMP-2 antibody were remarkably increased in VAS-HTN patients compared to EH and HC and might reflect the disease activity. The anti-LAMP-2 antibody may be a potential biomarker for diagnosis and estimating the disease activity in VAS-HTN.

Infection is associated with increased risk of MPO- but not PR3-ANCA-associated vasculitis.

To determine whether development of ANCA-associated vasculitis (AAV) shows a relationship with a prior infection and if prior infection affects disease characteristics and outcome. All incident cases of AAV diagnosed in a defined region of Sweden from 2000 through 2016 were identified. For each case, 10 individuals from the general population, matched for age, sex and area of residence, were selected. Infections occurring in AAV patients and controls prior to the date of AAV diagnosis (index date for respective controls) were identified using an administrative database. Conditional logistic regression models were used to calculate odds ratios (OR) of developing AAV. Occurrence, clinical characteristics and outcome of AAV were analysed with respect to prior infection. Two-hundred and seventy patients with AAV (48% female) and 2687 controls were included. Prior to diagnosis/index date, 146 (54%) AAV patients had been diagnosed with infection vs 1282 (48%) controls, with OR for AAV 1.57 (95% CI 1.18, 2.19) in those with infections of the upper respiratory tract and 1.68 (1.02, 2.77) in those with pneumonia. Difference from controls was significant in patients with MPO-ANCA 1.99 (95% CI 1.25, 3.1) but not in those with PR3-ANCA 1.0 (0.61, 1.52). Patients with prior infection showed higher disease activity at AAV diagnosis. No differences in disease characteristics, comorbidities or outcome in those with and without prior infections were observed. Respiratory tract infections are positively associated with development of MPO- but not PR3-ANCA vasculitis. Prior infection is associated with higher disease activity at AAV diagnosis.

Subclinical alterations in retinal layers and microvascular structures with OCTA in ANCA-associated vasculitides

ABSTRACT Purpose Using OCTA, investigate the capillary network and retinal layers in granulomatosis with ANCA associated vasculitis (AAV) patients who did not manifest apparent ocular involvement and compare the findings with healthy subjects. Method The present study, which is designed as a prospective and case-control study, includes 22 AAV patients and 35 control participants. OCTA parameters were noted. Results In most of the regions, AMT, RNFL and GC-IPL thicknesses were significantly lower in the AAV group than in the control group. While the vascular indices were lower in the AAV group, except for the center 1 mm region, the FAZ parameters were similar between the two groups. Conclusion In AAV patients, subclinical changes in the retinal layers and superficial vascular plexus have been shown. In the future maybe a non-invasive method such as OCTA will become available in scoring systems for prognosis determination in AAV.