Diagnosis Of Associated Vasculitis Research Articles

#2700 Serum C3/C4 levels in renal antineutrophil cytoplasmic antibody-associated vasculitis: predictors of lung disease and worse prognosis

Abstract Background and Aims Complement activation, specially the alternative pathway, has been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This was further corroborated with the efficacy of Avacopan, a selective C5a receptor inhibitor used as a corticosteroids reduction strategy in the treatment of AAV [1]. Low complement factor 3 (C3) levels without real hypocomplementemia are predictors of prognosis in AAV [2]. Low C4 levels have not yet been associated with worst outcomes. We aimed to evaluate the association between circulating C3 and C4 levels at diagnosis of AAV with clinical and biochemical features and with relevant outcomes: relapse, dialysis and death. Method This is a retrospective study including 63 patients with AAV with renal involvement followed between 2003-2023, with C3 and C4 levels measurements at diagnosis. Data was recorded from clinical registries. Patients were grouped according to the median C3 and/or C4 levels, as previously performed [2]. Groups were compared using the chi-square test for categorical variables and non-parametric tests for continuous variables. We created a logistic regression model for the outcomes, adjusting for covariates. Results Mean age at diagnosis was 61.1 ± 13.4 years old and most patients had ANCA MPO specificity (69.8%, n = 44). Only 3 patients had low C3 levels (< 83 mg/dL) and C4 hypocomplementemia (<12 mg/dL) was present in other 3 patients. Median C3 levels were 127.5 mg/dL (107.3-139.0) and median C4 levels were 29.5 mg/dL (22.0-35.0). Groups were defined according to these values: low C3 levels (C3 <127.5 mg/dL, n = 31), low C4 levels (C4 <29.5 mg/dL, n = 31) and low C3 and/or C4 levels, when either of these conditions were met (n = 40). There was a positive correlation between C3 and C4 levels (r = 0.57, p < 0.001). Patients with low C3 levels had more frequent lung involvement than patients with higher C3 levels (71% vs 31.3%, p = 002), as well as alveolar hemorrhage (38.7% vs 12.9%, p = 0.020). Regarding the outcomes, there was a tendency for more patients requiring acute dialysis (first month) and progressing to dialysis during follow-up in the low C3 subgroup. Relapse and death rates were similar between the two groups. Low C4 levels were associated with older age (75 ± 11.8 vs 67.5 ± 13.7 years, p = 0.043), higher relapse rates (50% vs 25.8%, p = 0.05) and faster progression to dialysis (1.0 (1.0-5.0) vs 9.5 (1.8-54) months, p = 0.034). When combining low C3 and/or C4 levels, lung involvement was again more frequent in patients with lower complement levels (62.5% vs 30.4%, p = 0.014). Time to dialysis was lower and relapse rates were higher in the subgroup with low complement levels, but not statistically significant. No association with death was found. Interestingly, acute dialysis requirement was more prevalent in the low C3/C4 levels subgroup (32.5% vs 8.7%, p = 0.033). After adjustment for baseline renal function, low C3/C4 levels showed an increase of 7 times the odds of a patient requiring acute dialysis (OR 6.98; 95% CI 1,196-40,839, p = 0.031, Table 1). Low C3/C4 levels independently predicted the odds of lung disease in AAV (OR = 5,069; 95% CI 1,475-17,612 p = 0.010, Table 2). Conclusion Complement activation in AAV has been previously associated to renal outcomes, but our results also highlight a possible role of complement in the pathophysiology of lung disease. Low C4 levels were associated with higher relapse rates and faster progression to dialysis, revealing that C4 activation impacts outcomes in AAV and that both classic and alternative complement pathways are involved. Combining low C3 and/or C4 levels identified patients at higher risk of acute dialysis requirement, independently of renal function at admission. Further insights in the specific effects of C3/C4 are needed to stipulate the value of monitoring and targeting complement factors in AAV.

#1337 Evolution of ANCA-associated vasculitis in a population with confirmed renal involvement. Myeloperoxidase and proteinase 3 antibodies, which is worse?

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare but potentially serious diseases with high mortality. Renal involvement is frequent in AAV with patients developing end-stage renal disease (ESRD) or becoming dependent on dialysis in up to 23% of patients. Several studies suggest the presence of clinical factors as predictors of survival in these diseases. The objective of this study was to analyze clinical evolution of AAV and to identify potential risk factors for developing renal events (ESRD or dialysis) and death in patients with AAV, with special attention to the implications that the presence of myeloperoxidase (MPO) or proteinase 3 (PR3) antibodies at diagnosis may have on the disease progression. Method We conducted a retrospective observational study of patients under follow-up for AAV. We considered only those with a confirmed diagnosis of AAV through renal biopsy for the present study. We collected clinical and laboratory variables at the time of disease presentation. We divided the patients based on the presence of MPO or PR3. Subsequently, we analyzed the patients' progression towards the occurrence of renal events (ESRD or dialysis) and mortality. Results Out of the 42 studied patients, 29 were MPO-positive and 13 were PR3-positive. We observed statistically significant differences in age and the frequency of hypertension, with the MPO group being older and more hypertensive than the PR3 group. On the contrary, PR3-positive patients exhibited a higher percentage of diabetes and increased severity of vasculitis at diagnosis as measured by the Birmingham Vasculitis Activity Score (BVAS). While most MPO-positive patients met criteria for microscopic polyangiitis (MPA), all PR3-positive patients met criteria for granulomatosis with polyangiitis (GPA) according to the ACR/EULAR 2022 guidelines. There were no statistically significant differences regarding clinical or laboratory variables analyzed, neither with induction nor maintenance treatment. We did not observe differences in the progression towards renal events or mortality between groups. However, we did observe a higher percentage of disease recurrence among PR3-positive patients (Table 1). Conclusion There were no statistically significant differences observed in the progression towards renal events (ESRD and dialysis) or mortality regardless of MPO or PR3 antibodies.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients’ clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the “dominant” phenotype in idiopathic double-positive AAV.

Thyroid disease in ANCA-associated vasculitis: a clinical and epidemiological study

ObjectivesTo describe clinical and laboratory characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and thyroid disease (TD). We also aimed to calculate incidence and identify predictors...

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV. Using data from the 2016-2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype. We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively). AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

Antineutrophil cytoplasmic antibody-associated vasculitis with predominant truncal muscle weakness: a retrospective case series.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to mononeuritis multiplex, which are characterized by distal weakness associated with sensory disturbances. Although AAV has also been reported to be associated with myopathy, the pathogenesis and characteristics remain unclear. We aimed to show the clinical and laboratory findings in AAV-associated myopathy. This retrospective single-center study included patients with the diagnosis of AAV who had been admitted to the neurology department and had biopsy specimens of muscle and/or nerve tissue. We identified four patients with a distinct clinical presentation of muscle weakness in the trunk and proximal limbs. The weakness resembled that of inflammatory muscle disease. These patients denied symptoms associated with neuropathy, and had normal serum creatine kinase (CK) levels. Needle electromyography (needle EMG) showed spontaneous electrical activity at rest, and results of magnetic resonance imaging (MRI) suggested inflammatory myopathy. Muscle biopsy specimens from all four patients revealed vasculitis and inflammation in proximity to the affected vessels, without any discernible characteristics of other myopathies. The patients also complained of symptoms affecting other organs, such as the ears and kidneys, which is typical of AAV cases. Remission induction therapy, such as cyclophosphamide pulse therapy in addition to oral prednisolone, were effective for all four patients. However, relapses occurred in two patients during maintenance therapy and two patients died of aspiration pneumonia. The clinical course of our patients might represent a subtype of AAV that is characterized by muscle weakness of the trunk and proximal extremities and arises from vasculitis within the muscles. The clinical manifestations of our patients were similar to those of patients with inflammatory myopathy with regard to the distribution of muscle weakness, MRI and needle EMG findings. However, there are notable differences between AAV associated myopathy vs. inflammatory myositis like dermatomyositis; (1) the absence of elevated CK levels, (2) the presence of complications in other organs, (3) distinct pathological findings, and (4) severe outcomes. Awareness that AAV patients with muscle involvement could have a subtype of AAV that seriously affects various organs is critical for an accurate diagnosis and effective therapeutic management.

Large vessel involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV. Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between January 1, 2000, and December 31, 2021, were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA, or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit. The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA; 13 had c-ANCA and/or PR3-ANCA. Mean (SD) age at AAV diagnosis was 63.4 (12.79); 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a one-year timespan. Twenty-five (69%) patients had histopathologic confirmation of AAV diagnosis in a location other than temporal artery, aorta, or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36), and methotrexate (18/36) were the most frequent treatments. This is the largest single-center cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

The role of anti-HMGB1 antibody and anti-moesin antibody in ANCA-associated vasculitis

ObjectiveThe study aims to evaluate the role of anti-high mobility group box 1 (HMGB1) antibody and anti-moesin antibody in the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its possible relationship with the different clinical manifestations. MethodsThe study involved 60 AAV patients, 58 patients with autoimmune disease other than AAV and 50 healthy subjects. The serum levels of anti-HMGB1 and anti-moesin antibodies were determined by enzyme-linked immunosorbent assay (ELISA), and the second determination was made 3 months after treatment of AAV patients. ResultsSerum levels of anti-HMGB1 and anti-moesin antibodies in AAV group were significantly higher than those in non-AAV group and HC group. The area under the curve (AUC) of anti-HMGB1 and anti-moesin in diagnosing AAV were 0.977 and 0.670, respectively. Anti-HMGB1 levels were significantly elevated in AAV patients with pulmonary involvement, while the concentrations of anti-moesin were significantly increased in patients with renal damage. Anti-moesin were positively correlated with BVAS (r=0.261, P=0.044), creatinine (r=0.296, P=0.024) and negatively correlated with complement C3 (r=−0.363, P=0.013). Besides, anti-moesin levels of active AAV patients were significantly higher than those in inactive patients. The concentrations of serum anti-HMGB1 could be significantly decreased after induction remission treatment (P<0.05). ConclusionAnti-HMGB1 and anti-moesin antibodies play important roles in the diagnosis and prognosis of AAV, which may act as potential disease markers for AAV.

Intravenous immunoglobulin therapy in antineutrophil cytoplasmic antibody-associated vasculitis

IntroductionAnti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes three heterogeneous and difficult to treat clinical entities. Intravenous immunoglobulins (IVIG) may constitute a good therapeutic option, although data hitherto are scarce. The aim of this study was to assess the effectiveness and safety of IVIG in AAV in a real-world setting. MethodsSingle center observational study of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. AAV diagnosis was based on a compatible clinical presentation and positive ANCA serology and/or compatible histology. Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). The effectiveness was evaluated by clinical and laboratory parameters (CRP, ESR) and its glucocorticoid-sparing effect. These variables were measured at one, six, twelve and twenty-four months of IVIG treatment. The doses of IVIG were 2g/kg in the following cycles of administration: 1 g/kg/day in 2 days (n=12); 0.5 g/kg/day in 4 days (n=11); 0.4 g/kg/day in 5 days (n=5). The clinical improvement was classified according to BVAS categories in remission, partial response and no response. ResultsTwenty-eight patients (15 granulomatosis-polyangiitis, 10 microscopic polyangiitis and 3 eosinophilic granulomatosis with polyangiitis) were included. Reasons for using IVIG were relapse/refractory disease (n=25), active or suspected infection (n=3), and both (n=5). We observed a rapid and maintained BVAS score improvement, increasing from 34.6% at 1 month to 56.5% at 2 years of follow-up (p=0.12), and a reduction of glucocorticoids dose. Therapy was well tolerated and adverse events mild and scarce. ConclusionIVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV or in presence of a concomitant active infection.

The factors predicting development of serious infections in ANCA-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease usually involving small vessels and progressing with necrotizing inflammation. Treatment requires long-term use of immunosuppressive agents to inhibit disease activity. Serious infections (SIs) are a common complication in AAV. The aim of this study was to identify the risk factors for serious infections which required hospitalization in patients with AAV. In this retrospective cohort study., we included 84 patients admitted to the Ankara University Faculty of Medicine in the last 10 years with a diagnosis of AAV. In 42 (50%) of 84 patients followed up with the diagnosis of AAV, an infection requiring hospitalization was identified. The patients' total corticosteroid dose, use of pulse steroids, induction regimen, levels of C-reactive protein (CRP) and the presence of pulmonary and renopulmonary involvement were found to be associated with the frequency of infection (p=0.015, p=0.016, p=0.010, p=0.03, p= 0.026 and p=0.029, respectively). In multivariable analysis, it was found that renopulmonary involvement (p=0.002, HR=4.95, 95% CI= 1.804-13.605), age of over 65 (p=0.049, HR=3.37, 95% CI=1.004-11.369) and high CRP levels (p=0.043, HR=1.006, 95% CI=1.000-1.011) constituted independent predictors of serious infection risk. The frequency of infection is known to be increased in ANCA-associated vasculitis. Our study showed that renopulmonary involvement, age and elevated CRP levels on admission are independent risk factors of infection.

Total Globulin Fraction at Diagnosis Could Forecast All-Cause Mortality during the Disease Course in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Total globulin fraction (TGF) is calculated by subtracting serum albumin levels from serum total protein levels. The present study examined whether TGF at diagnosis could forecast all-cause mortality during the disease course in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The present study included 283 patients with AAV. The variables at AAV diagnosis such as demographic data, AAV-specific data including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and laboratory data including ANCA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were collected. The number of deceased patients during the follow-up duration based on all-cause mortality was counted. The median age of the 283 AAV patients was 60 years, and 35.7% were men. ANCAs were detected in 228 patients, and the median TGF was 2.9. A total of 39 patients (13.8%) died within a median follow-up duration of 46.9 months. TGF at AAV diagnosis was significantly correlated with ESR and CRP rather than AAV activity. Patients with ANCA positivity exhibited a significantly higher median TGF at AAV diagnosis than those without. Patients with TGF ≥ 3.1 g/dL at AAV diagnosis exhibited a significantly lower cumulative survival rate than those without. Furthermore, in the multivariable Cox hazards model analysis, TGF ≥ 3.1 g/dL (hazard ratio 2.611) was independently associated with all-cause mortality, along with age, male sex, and body mass index. The present study is the first to demonstrate that TGF at AAV diagnosis can forecast all-cause mortality during the disease course in AAV patients.

#5894 HYPOCOMPLEMENTEMIA AT DIAGNOSIS OF ANCA-ASSOCIATED VASCULITIS IS ASSOCIATED WITH SEVERITY AND OUTCOMES

Abstract Background and Aims A relationship between antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and complement has been shown, and complement has an important role in the pathogenesis of AAV [1]. Low serum complement levels (sC3) at diagnosis of AAV has been previously described although clinical characteristics and outcomes of AAV with hypocomplementemia still remain unclear [2]. The aim of this study was to investigate what proportion of patients with AAV have low sC3 at diagnosis, and whether they have different clinical and histological features or experience different outcomes compared to patients with normal sC3. Method A total of 93 patients with AAV diagnose (81,3% Anti-MPO and 18,7% anti-PR3) were included in the study from 2000-2022. 12% of them had sC3 values below limit of normal range (i.e., &amp;lt;90 mg/dl). Patients were categorized according to sC3 levels into 2 groups, hypocomplementemic (G1; mean C3: 73.1mg/dl), and normocomplementemic (G2; mean C3: 128.3mg/dl). Histological patterns were based on the Berden score and correlated with clinical features. Main outcomes of interest included severity of acute kidney injury at diagnose (AKI), histopathological patterns, end-stage kidney disease (ESKD) and death in the long term. Results No differences were identified in terms of demographics (age, gender, induction treatment). sC3 levels and serum creatinine were statistically associated (r2:-0.40; p&amp;lt;0.001). Patients with low sC3 had more severe renal involvement, at diagnose (G1: sCr 7.6mg/dl vs sCr 3.8mg/dl, p&amp;lt;0.001) without differences in ANCA levels and they were more likely to require acute dialysis around the initial diagnosis (p &amp;lt; 0.01). There were significant differences in sCr levels at diagnose (p&amp;lt;0.001) related to Berden score without differences in sC3 levels (Focal, n = 8 (8.6%), sCr 2.5 mg/dl, sC3 121.1 mg/dl; Crescentic, n = 23 (24.7%), sCr 6.41mg/dl, sC3 119.3 mg/dl; Mixed n = 16 (17.2%), sCr 3.6mg/dl, sC3 118.5 mg/dl; Sclerotic, n = 14 (15.1%) sCr 3.0 C3 129.1mg/dl). 55.5% of G1 patients deceased compared to 28% of G2. Lower sC3 levels (G1) were associated with mortality (log-rank 4.1; p&amp;lt;0.05) and composite outcome of ESKD or death (log-rank 5.9; p&amp;lt;0.05) compared G2 patients. Conclusion Hypocomplementemia in AAV at the disease onset was a risk factor for the serious organ damage, and a life prognostic factor. Low C3 levels at diagnosis of AAV is emerging as a predictor of renal outcomes and it is thus very important to pay attention to them. Despite that histologic patterns of the Berden classification were related to the severity of AKI at presentation there was no statistical correlation with sC3 levels. We recommend to pay attention to the levels of complement at the diagnosis of AAV.

#4661 KIDNEY TRANSPLANTATION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS IS ASSOCIATED WITH A HIGH INCIDENCE OF POST-TRANSPLANT CANCER

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are challenging systemic diseases. Kidney transplantation is the treatment of choice for patients with AAV and end stage kidney disease.[1] AAV relapses after transplantation are rare and data regarding AAV recurrences in this setting are lacking.[2] Method In this single-centre retrospective cohort study, we analyzed the data from medical records of adult patients transplanted at our transplant Center between February 2006 and January 2022 and followed at the Nephrology Unit of the same Hospital: Fondazione IRCCS Cà Granda Ospedale Policlinico in Milan. Results We identified 9 patients on 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplant was tacrolimus-based in 89% of the patients. At the end of a median follow-up of 132 ± 61.1 months after transplantation, only one case of extra-renal vasculitis relapse was observed (Table 1). The relapse rate was 0.01 per patient per year comparable to what reported in the literature. However, seven patients were diagnosed with cancer after a median follow-up of 81.4 ± 35.8 months after transplantation; six had skin cancer and three a renal cell carcinoma of the native kidneys (cumulative incidence of 78%). One patient died from metastatic spinous cell carcinoma. We therefore decided to make a narrative comparison between this cohort and a previous series published by our group including 19 patients transplanted between December 1987 and January 2006.[3] In the older cohort we reported 7 relapses and a relapse-rate of 0.076 per patient per year (Table 2). Conclusion In conclusion, compared with previous data from our group (December 1987-January 2006), we found a consistent decrease in disease relapse (7 relapse in 19 patients previous cohort vs 1 relapse in current cohort) in kidney transplant patients with AAV, followed by the appearance of post-transplant cancer. This result could be attributable to the use of more powerful immunosuppression a deserved particular attention in the follow up of AAV patients after kidney transplantation.

AB1681 ARE PR3 ANTIBODY TITERS REALLY IMPORTANT FOR ROUTINE CLINICAL PRACTICE?. STUDY FROM A SINGLE UNIVERSITY HOSPITAL

BackgroundAnti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-proteinase 3 are one of the main ANCA subtypes. There are contradictory studies on the relation between ANCA levels and the severity of the disease and its prognosis [1].ObjectivesIn patients with positive anti-PR3 antibodies from a university hospital we assess:a) associated diseases,b) specificity in diagnosing AAV and,c) determine if there is a cut-off point that allows to correlate the levels of anti-PR3 antibodies with the severity and prognosis of AAV.MethodsObservational study of patients with positive anti-PR3 from a University Hospital, from 2003 to 2022. ANCA was determined by chemiluminescence.The specificity of anti-PR3 for AAV diagnosis, predictive value of severity and prognosis were determined with Receiver Operating Characteristic (ROC) curves.At diagnosis, AAV with renal disease (hematuria and/or proteinuria) and lung involvement (hemoptysis, asthma and/or respiratory failure) were considered severe.During follow-up, the prognosis was considered worse if the patient needed dialysis, a transplant, or died.ResultsWe study 54 patients with positive PR3. Most of them (81.5%) had an underlying AAV being the most frequent GPA (61.1%). The non vasculitic disease more frequent was Ulcerative colitis (11.1%).Table1 summarizes the prevalence of these antibodies in different diseases. The frequencies are equivalent to those previously described and it is noteworthy the presence of anti-PR3 in drug-induced vasculitis, mainly by cocaine.Anti-PR3 antibodies for a diagnosis of vasculitis (n=44), an area under the curve (AUC) was calculated (AUC=0.7318), and a cut-off point of 20.5 IU/ml was determined(Figure 1).Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n=30) and those without them (n=24) (p=0.0048), and a cut-off threshold of 41.5 IU/ml was established.Finally, after examining the illness’s prognosis an AUC= 0.5643 was obtained, being no significant differences between those patients who had a worse disease progression (n=14) and those who did not (n=40) (p=0.4847).ConclusionThe presence of anti-PR3 is mainly associated with AAV, although in up to a fifth of cases it can be associated with other diseases.Anti-PR3 antibodies levels, at the moment of AAV diagnosis, correlates with disease diagnosis (specificity) and with severity but not with disease outcome.

The role of anti-HMGB1 antibody and anti-moesin antibody in ANCA-associated vasculitis

ObjectiveThe study aims to evaluate the role of anti-high mobility group box 1 (HMGB1) antibody and anti-moesin antibody in the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its possible relationship with the different clinical manifestations. MethodsThe study involved 60 AAV patients, 58 patients with autoimmune disease other than AAV and 50 healthy subjects. The serum levels of anti-HMGB1 and anti-moesin antibodies were determined by enzyme-linked immunosorbent assay (ELISA), and the second determination was made 3 months after treatment of AAV patients. ResultsSerum levels of anti-HMGB1 and anti-moesin antibodies in AAV group were significantly higher than those in non-AAV group and HC group. The area under the curve (AUC) of anti-HMGB1 and anti-moesin in diagnosing AAV were 0.977 and 0.670, respectively. Anti-HMGB1 levels were significantly elevated in AAV patients with pulmonary involvement, while the concentrations of anti-moesin were significantly increased in patients with renal damage. Anti-moesin were positively correlated with BVAS (r=0.261, P=0.044), creatinine (r=0.296, P=0.024) and negatively correlated with complement C3 (r=−0.363, P=0.013). Besides, anti-moesin levels of active AAV patients were significantly higher than those in inactive patients. The concentrations of serum anti-HMGB1 could be significantly decreased after induction remission treatment (P<0.05). ConclusionAnti-HMGB1 and anti-moesin antibodies play important roles in the diagnosis and prognosis of AAV, which may act as potential disease markers for AAV.

Earliest total vascular damage index scores independently predict all-cause mortality in patients with ANCA-associated vasculitis.

This study investigated whether the earliest total Vasculitis Damage Index (VDI) score could significantly predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study included AAV patients who were first diagnosed at this hospital from 2001 to 2022. The earliest total VDI score was defined as the first VID assessed more than 3 months after AAV diagnosis in 93.5% of patients or after the first AAV presentation in 6.5% of patients. The optimal cut-off of the earliest total VDI score for all-cause mortality was obtained using the receiver operating characteristic curve. The median age and earliest VDI score were 60.0 years (35.5% men), and 3.0. The most common damaged system in the earliest VDI was the pulmonary (55.3%) system. Among the AAV patients, 39 (13.3%) died. When the optimal cut-off of the earliest total VDI score for all-cause mortality was set at 3.0 (sensitivity 64.1%, specificity 75.2%), AAV patients with the earliest total VDI score ≥3.0 exhibited a significantly higher risk for all-cause mortality than those without (relative risk 6.090). AAV patients with the earliest total VDI score ≥3.0 exhibited a significantly lower cumulative patients' survival rate than those without. In the multivariable Cox hazards model analyses, not only the earliest total VDI score but also the earliest total VDI score ≥3.0 were independently associated with all-cause mortality. This study was the first to demonstrate that the earliest total VDI score could predict all-cause mortality during follow-up in AAV patients.

Assessment of longitudinal serum neutrophil extracellular trap–inducing activity in anti-neutrophil cytoplasmic antibody–associated vasculitis and glomerulonephritis in a prospective cohort using a novel bio-impedance technique

Neutrophil extracellular traps (NET) have been implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we developed a novel, label-free, high-throughput bio-impedance technique to effectively measure serum NET-inducing activity. Using this technique, NET-inducing activity of serum derived from patients with AAV was assessed in a prospective cohort of 62 patients presenting with active AAV with major organ involvement. Thirty-five patients presented with new and 27 patients presented with relapsing AAV, of whom 38 had kidney and/or 31 had lung involvement. NET-inducing activity was assessed at diagnosis of active AAV (time zero), during the first 6 weeks of treatment, and after 6 months of treatment. Forty-seven patients revealed elevated NET-inducing activity at time zero. After initiation of immunosuppressive treatment, NET-inducing activity was reduced at six weeks. A subsequent increase at six months could potentially identify patients with relapsing disease (hazard ratio, 11.45 [interquartile range 1.36-96.74]). NET-inducing activity at time zero correlated with kidney function and proteinuria. Importantly, in kidney tissue, NETs co-localized with lesions typical of ANCA-associated glomerulonephritis and even correlated with systemic serum NET-inducing activity. Thus, our prospective data corroborate the importance of NET formation in AAV and ANCA-associated glomerulonephritis and the potential of longitudinal evaluation, as monitored by our novel bio-impedance assay and detailed histological evaluation.

Acute coronary syndrome in antineutrophil cytoplasmic antibody-associated vasculitis: a Korean single-centre cohort study.

This study investigated the incidence and patterns of the acute coronary syndrome (ACS) after AAV diagnosis and searched for the predictors of ACS in a single-centre cohort of Korean patients diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A total of 262 patients with AAV were included in this study. ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina (UA) were defined as ACS in this study. Only ACS that occurred during or after AAV diagnosis was counted. The incidence of ACS in patients with AAV was 2.7% (7 patients), and the most common type of ACS was NSTEMI regardless of the affected site or the number of coronary arteries. Five patients with ACS were diagnosed with microscopic polyangiitis (MPA) and all of them had myeloperoxidase (MPO)-ANCA (or perinuclear [P]-ANCA), whereas the remaining two patients were diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Of the seven patients, 2 patients experienced ACS within the first year after AAV diagnosis, and 2 experienced ACS 5 years after AAV diagnosis. Among clinical variables, only the male sex was a predictor of ACS during the follow-up period in patients diagnosed with AAV. The incidence of ACS was 2.7%, and the most common type of ACS was NSTEMI in Korean patients with AAV.

Traditional and disease specific risk factors for cardiovascular events in ANCA-associated vasculitis: a multinational retrospective study.

To investigate the occurrence of cardiovascular events (CVE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, China, Turkey, Russia, UK, and USA. Patients with a definite diagnosis of AAV who were followed ≥3 months and had sufficient documentation were included. Data on myocardial infarction (MI) and stroke were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Over a median follow-up of 62 (interquartile range: 23, 100) months, CVE (mostly MI) occurred in 245 (10.7%) of 2286 AAV patients with a higher frequency in China and the UK. On multivariate regression analysis, older age (55-64.9 years; HR 2.93, 95% CI: 1.99, 4.31), smoking (HR 1.98, 95% CI: 1.48, 2.64), Chinese origin (HR 4.24, 95% CI: 3.07, 5.85), pulmonary (HR 1.50, 95% CI: 1.09, 2.06) and kidney (HR 3.02, 95% CI: 2.08, 4.37) involvement were independent variables associated with a higher occurrence of CVE. We showed that geographic region and both traditional and disease specific (kidney involvement in particular) factors were independently associated with CVE. Proper assessment and management of modifiable cardiovascular risk factors are essential for prevention of cardiovascular morbidity in AAV patients.