Antineutrophil Cytoplasmic Antibody Titers Research Articles

Methotrexate and Rituximab Use in Highly Recurrent Idiopathic Subglottic Stenosis.

To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(-). This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated. A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre-drug interval: 338; mean post-drug interval: 697 days) (p-value = 0.25). Three patients did not recur following drug initiation with median follow-up of 1265 days. All three treatment groups demonstrated a trend toward increased post-drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post-drug recurrence intervals (mean pre-drug interval: 341 days, mean post-drug interval 978 days) (p-value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%). MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy. 3 Laryngoscope, 2024.

Granulomatosis with polyangiitis masquerading as disseminated tuberculosis in presence of bilateral lung cavities and hemorrhagic infarct

Lung cavitations with constitutional symptoms are usually associated with pulmonary tuberculosis due to its high prevalence and are the most common infectious cause in India. Granulomatosis with polyangiitis (GPA) with the systemic pulmonary disease will have different radiological presentations such as nodule, mass, and consolidation with or without cavitation. In this case report, we have reported a 40-year-old female presented with cough, fever, and weight loss of 6 months duration with chest imaging suggestive of bilateral cavitary lung disease. She was labeled as a case of disseminated tuberculosis due to involvement of the central nervous system and empirically treated with anti-tuberculosis treatment (ATT) without microbiological evidence of tuberculosis in smear and cartridge-based nucleic acid amplification tests. The absence of clinical response and radiological worsening to empirical ATT gives a clue for an alternate diagnosis. Bronchoscopy workup documented Aspergillus colonization and vasculitis workup in the presence of cavitary lung disease documented abnormally raised proteinase 3 anti-neutrophil cytoplasmic antibodies titers. She was treated with a combination of systemic methylprednisolone and azathioprine with voriconazole. Her clinical response was observed in 4 weeks and radiological response with complete radiological clearance of pulmonary cavitations was documented after 6 months of treatment. We recommend prompt workup and ruling out GPA in all cases with pulmonary cavitations with negative microbiological workup and no empirical ATT should be given in the era of rapid microbiological tests with good sensitivity and specificity.

Diagnostic accuracy of ANCA serology in ANCA-associated vasculitis with renal involvement.

Pauci-immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end-stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well-established. We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. Eight hundred and forty-eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci-immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci-immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89-0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%-87.6%) and a specificity of 94.0% (95% CI: 91.6%-96.0%). ANCA titres are highly predictive of pauci-immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life-threatening disease.

First-year cumulative myeloperoxidase-ANCA titres are associated with all-cause mortality in patients with microscopic polyangiitis.

We investigated whether first-year cumulative myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3 (PR3)-ANCA titres were associated with all-cause mortality and relapse during follow-up in patients with microscopic polyangiitis (MPA) and granMETHODS: Altogether, 74 patients with MPA and 40 with GPA were included in this study. Their clinical data at diagnosis were collected. First-year cumulative ANCA titres were defined as the area under the curve (AUC) of ANCA titres during the first year after MPA or GPA diagnosis, which was obtained using the trapezoidal rule. All-cause mortality and relapse were considered poor outcomes of MPA and GPA. The median ages of patients with MPA and GPA were 65.5 and 60.5 years, respectively. No significant correlation was observed between ANCA titres at diagnosis and concurrent MPA and GPA activity or the inflammatory burden. First-year cumulative MPO-ANCA titres exhibited a significant AUC for all-cause mortality during follow-up in patients with MPA. The optimal cut-off of first-year cumulative MPO-ANCA titres for all-cause mortality was determined as 720.8 IU/mL using receiver operating characteristic curve analysis. MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly higher risk for all-cause mortality than those without (relative risk 13.250). Additionally, MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly lower cumulative patients' survival rate than those without. This is the first study to demonstrate the association between first-year cumulative MPO-ANCA titres and all-cause mortality during follow-up in patients with MPA.

Elevated plasma FXII is associated with disease activity in ANCA-associated vasculitis: A Retrospective Cross-Sectional Study in Western China

This study examined whether plasma FXII levels reflect disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Plasma FXII levels were detected by ELISA in 127 patients with AAV, and their associations with disease activity and plasma myeloperoxidase (MPO)-ANCA titre were examined. Immunofluorescent co-staining of FXII and neutrophils was performed on the renal tissues of patients with AAV. MPO expression in renal biopsy tissues was determined by immunohistochemical staining. The association between plasma FXII levels and histological activity was assessed in 82 patients who underwent kidney biopsy. Plasma FXII levels were considerably increased in patients with clinically active AAV compared to those in clinical remission and healthy individuals. Plasma FXII levels correlated positively with creatinine (r = 0.377), CRP (r = 0.222), urine red blood cell (r = 0.203), serum MPO-ANCA titer (r = 0.353), white blood cell (r = 0.194), percentage of glomeruli with crescents (P = 0.001), capillary breaks (P = 0.001), interstitial inflammation (P < 0.001) and fibrinoid necrosis (p < 0.001) on kidney biopsy. The plasma FXII optimal cut-off value for evaluating AAV activity was 24.5 μg/mL (sensitivity = 0.81, specificity = 0.82, P = 0.0001), which was superior to that achieved using conventional serologic biomarkers. Co-expression of FXII and neutrophils was higher, with increased MPO expression, in renal tissue with pathologically active AAV than that observed in pathologically inactive tissues. In conclusion, elevated plasma FXII levels reflect AAV clinical and histologic activity, and can serve as markers of active AAV.

Specific IgG glycosylation differences precede relapse in PR3-ANCA associated vasculitis patients with and without ANCA rise.

Immunoglobulin G (IgG) contains a conserved N-glycan in the fragment crystallizable (Fc), modulating its structure and effector functions. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) alterations of IgG Fc-glycosylation have been observed to correlate with the disease course. Here, we examined longitudinal changes in N-linked Fc glycans of IgG in an AAV patient cohort and their relationship with disease flares. Using liquid chromatography coupled with mass spectrometry, we analysed IgG Fc-glycosylation in 410 longitudinal samples from 96 individuals with AAV. Analysis of the cross-sectional differences as well as longitudinal changes demonstrated that IgGs of relapsing PR3-ANCA patients have higher ΔFc-bisection at diagnosis (P = 0.004) and exhibit a decrease in Fc-sialylation prior to the relapse (P = 0.0004), discriminating them from non-relapsing patients. Most importantly, PR3-ANCA patients who experienced an ANCA rise and relapsed shortly thereafter, exhibit lower IgG Fc-fucosylation levels compared to non-relapsing patients already 9 months before relapse (P = 0.02). Our data indicate that IgG Fc-bisection correlates with long-term treatment outcome, while lower IgG Fc-fucosylation and sialylation associate with impending relapse. Overall, our study replicated the previously published reduction in total IgG Fc-sialylation at the time of relapse, but showed additionally that its onset precedes relapse. Furthermore, our findings on IgG fucosylation and bisection are entirely new. All these IgG Fc-glycosylation features may have the potential to predict a relapse either independently or in combination with known risk factors, such as a rise in ANCA titre.

CD47 blockade ameliorates autoimmune vasculitis via efferocytosis of neutrophil extracellular traps.

Neutrophil extracellular trap (NET) formation contributes to immune defense and is a distinct form of cell death. Excessive NET formation is found in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), contributing to disease progression. The clearance of dead cells by macrophages, a process known as efferocytosis, is regulated by the CD47-mediated "don't eat me" signal. Hence, we hypothesized that pathogenic NETs in AAV escape from efferocytosis via the CD47 signaling pathway, resulting in the development of necrotizing vasculitis. Immunostaining for CD47 in human renal tissues revealed high CD47 expression in crescentic glomerular lesions of patients with AAV. In ex vivo studies, ANCA-induced netting neutrophils increased the expression of CD47 with the reduction of efferocytosis. After efferocytosis, macrophages displayed pro-inflammatory phenotypes. The blockade of CD47 in spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mice ameliorated renal disease and reduced myeloperoxidase (MPO)-ANCA titers with a reduction in NETs formation. Thus, CD47 blockade would protect against developing glomerulonephritis in AAV via restored efferocytosis of ANCA-induced NETs.

Clinical efficacy of protein A immunoadsorption therapy on severe ANCA-associated vasculitis renal injury.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases involving multiple systems, and kidney is one of the most commonly involved target organs. Some patients may rapidly progress to end-stage renal disease in a short time. Whereas some patients have poor remission and renal prognosis after standard induction therapy. As a selective blood purification therapy, protein a immunoadsorption (PAIA) has shown great advantages on treating of severe autoimmune diseases. This study aims to evaluate the short-term efficacy of PAIA therapy combined with glucocorticoids and immunosuppressants on treating of severe AAV renal injury. A total of 10 AAV cases with severe kidney involvement in the Second Xiangya Hospital of Central South University from 2019 to 2020 were selected for this retrospective study. During the induction remission stage, each patient was treated with PAIA on the basis of standard therapy of glucocorticoids and immunosuppressive treatment. Before and after the initial treatment, 1 month and 3 months after treatment, clinical data including demographic characteristics, immunological indicators, and Birmingham Vasculitis Activity Score (BVAS) were compared. The related adverse reactions during treatment were recorded to evaluate the short-term efficacy. In this study, all 10 patients were MPO positive, and 2 patients were PR3 positive (≥2.3 U/mL). There are 6 males and 4 females at (61.5±11.4) years old, with the median time from onset to admission to hospital at (2.8±1.8) months. Multisystem damage, especially kidney damage, can be seen with eGFR lower than 30 mL/(min·1.73 m2). During the 3-month follow-up, BVAS, erythrocyte sedimentation rate, and hemoglobin of 10 patients showed continuous improvement compared with the initial admission levels (all P<0.05). ANCA titer, serum creatinine and urine red blood cell were all decreased and eGFR levels were increased in 3 months after treatment (all P<0.05). Serum albumin, urinary protein, C-reactive protein and complement levels showed no significant changes after treatment (all P>0.05). One patient who had received renal replacement therapy was still dialysis dependent after PAIA treatment. One patient who had transient hypotension was corrected by routine treatment. The rest of the patients were all tolerant with PAIA during their treatments. Treatment with PAIA combined with glucocorticoids and cyclophosphamide can rapidly lower serum ANCA level and improve disease activity in patients with AAV complicated with severe kidney damage, suggesting a good short-term renal prognosis and good overall safety.

Increased factor XI but not factor XII is associated with enhanced inflammation and impaired fibrin clot properties in patients with eosinophilic granulomatosis with polyangiitis.

In eosinophilic granulomatosis with polyangiitis (EGPA) a prothrombotic state, including formation of denser fibrin networks with reduced lysability has been observed. Little is known about the intrinsic pathway in EGPA. We investigated whether coagulation factors (F)XI and FXII are associated with eosinophil-driven prothrombotic state. In 34 consecutive EGPA patients with remission we assessed FXI and FXII levels along with plasma fibrin clot permeability (Ks), fibrin clot morphology using scanning electron microscopy, and efficiency of fibrinolysis, expressed as lysis time (t50%) and maximum rate of increase in D-dimer levels (D-Drate). Increased FXI level (>130%, the upper reference limit) was found in 8 (23.5%) patients. Compared to patients with FXI levels ≤130%, those with increased FXI had higher eosinophil count (+365%) and reduced percentage of neutrophils (-20.4%), along with reduced Ks (-20.5%). In patients with FXI>130% clots were composed of thinner fibrin fibers (-17.5%). FXI was not associated with C-reactive protein and fibrinogen levels or anti-neutrophil cytoplasmic antibodies titers. There were no correlations between FXI and FXII levels as well as between FXII and eosinophil count (all p>0.05). To our knowledge, this study is the first to show association between FXI and a prothrombotic state in EGPA. Given clinical trials on FXI inhibition as an antithrombotic option, our findings suggest that this therapeutic approach could be useful in diseases with hypereosinophilia.

Clinical features and outcomes of patients with antineutrophil cytoplasmic antibody-positive systemic lupus erythematosus

Purpose To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China. Methods This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR). Results Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008). Conclusion Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement.

#4790 SERUM BIOMARKERS AS PREDICTORS OF RENAL DAMAGE IN ANCA-ASSOCIATED VASCULITIDES

Abstract Background and aims Despite therapeutic advances, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) carry poor renal and survival outcomes. Prognostic elements are needed to guide treatment. Several studies explored determinants of AAV outcomes, but predictive factors are not well established. Poor prognosis factors have been lower glomerular filtration rate, lower serum C3, C3 deposition on immunofluorescence (IF), and recently platelet count below 250 × 109/L. Histopathological lesions have also been related to renal outcomes. In this study we aim to correlate serum immune and inflammatory biomarkers with renal histological lesions’ severity. Methods We retrospectively analysed histopathological findings of adults with biopsy-proven AAV renal involvement through Berden's histopathological classification (BHC) classes, Brix's renal risk score (BRS), interstitial fibrosis and tubular atrophy (IFTA) and crescentic glomeruli percentages (%), C3 positive IF and presence of interstitial hemorrhage (IH). Patients’ ANCA titer (ANCAd) measured by ELISA, serum C3 and C-reactive protein (CRP) were documented at diagnosis. ANCA titer was also registered at last follow-up date (ANCAf). Univariate statistical analysis was used to correlate every biomarker with every histologic variable mentioned. C3 and CRP were used as continuous variables and ANCA titers as continuous and categorical variables. As a continuous variable, ANCA titers above laboratorial detection were not considered (i.e. &amp;gt;134). Seronegative AAV were not considered for titer analysis. BRS was considered as continuous variable for its score and as categorical for its risk group. Multivariate analysis was used to identify independent predictors renal biopsy findings. Results We included 46 patients with biopsy-proven AAV kidney involvement from January 2006 to January 2023, 65.2% male (n = 30), median age 66.5 (60.75-74.5), 78.3% (36) MPO, 15.2% (7) PR3 and 6.5% (3) seronegative; and 6.5% (3) had concomitant anti-GBM+ (all MPO). Categorization by ANCAd revealed 7.7% (3) 0-19 UI/mL, 7.7% (3) 20-39, 7.7% (3) 40-59, 20.5% (8) 60-99, 12.8% (5) 100-134 and 43.6% &amp;gt;134. According to BHC, biopsies were: 17.4% (8) global sclerotic, 28.3% (13) mixed, 39.1% (18) crescentic, and 15.2% (7) focal. According to BRS, 2.2% (1) had low risk, 28.3% (13) medium risk and 58.7% (27) high risk of ESKD. 5 biopsies had incomplete information for a score result. Median BRS was 9 – high risk. IF C3 was positive 28.3% (16) biopsies, and IH in 10.9% (5). Median % IFTA was 40% and median %crescentic was 33%. In univariate analysis, ANCAd did not correlate to BHC class both as continuous and categorical variable (p = 0.477 and p = 0.685 respectively), nor to %IFTA (p = 0.935, p = 0.938), nor %crescents (p = 0.975, p = 0.938), nor C3 IF staining (p = 0.690, p = 0.344), nor IH presence (p = 0.773, p = 0.897), nor to BRS risk groups (p = 0.339, p = 0.584). ANCAd titer did not correlate to BRS score value (p = 0.072, r = 0.372), both as continous variables. However, ANCAf did correlate to BRS´s risk groups (p = 0.037), with ANCAf values higher in the high-risk compared to the medium-risk group (p = 0.016). In multivariate analysis including age and gender, ANCAf persists as a predictor of BRS´s risk groups (p&amp;lt;0.001, model p&amp;lt;0.001). C3 levels at diagnosis did not have statistically significant correlation with neither histological finding: BHC class (p = 0.282), BRS score (p = 0.683), % IFTA (p = 0.753), % crescents (p = 0.989), C3 on IF (p = 0.472) and IH (p = 0.773). No significant correlation was seen when considering CRP at diagnosis: BHC class (p = 0.162), BRS (p = 0.276), %IFTA (p = 0.343), %crescents (p = 0.071), C3 on IF (p = 0.657) and IH (p = 0.951). Conclusions ANCA titer at diagnosis, serum C3 and CRP did not correlate with histological severity and chronicity lesions in our population. Nonetheless, larger cohorts, systematization of biopsy findings and studies on newer biomarkers might bring helpful information to expected prognosis and initial therapeutic approaches. A positive correlation between ANCA levels at the last follow-up date and medium and high-risk BRS groups on initial biopsy might be further explored in larger studies.

#4773 INFECTIVE ENDOCARDITIS COMPLICATED BY RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS: BEYOND ANTIBIOTICS - TO TREAT OR NOT TO TREAT?

Abstract Background A significant proportion of patients with infective endocarditis, present with acute renal failure related to infective endocarditis-associated glomerulonephritis (IEAGN). However, IEAGN differs from other infection-related glomerulonephritis because it may present with clinical and serological disturbances resembling autoimmune diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Its development introduces the dilemma of determining the best treatment approach. Immunosuppressive therapy added to antibiotic treatment may be beneficial for recovery of renal function in some cases of IEAGN with positive ANCA serology, although this approach is still controversial. Case presentation A 32-year-old man presented with fever, fatigue, purpura and rapidly progressive glomerulonephritis. He had a history of atrioventricular septal defect corrected at 9 years of age. Blood analysis showed anemia, acute kidney injury and positive ANCA proteinase 3 (PR3). Urine analysis revealed hematuria and proteinuria. Echocardiogram showed vegetation on the mitral valve with moderate to severe mitral regurgitation. Blood cultures showed Streptococcus mitis. After 14 days of intensive antibiotic regimen, kidney function rapidly deteriorated and ANCA titers remained high. A renal biopsy was performed and showed crescentic necrotizing glomerulonephritis with deposition of C3 and IgM – compatible with infection-related glomerulonephritis. Treatment was initiated with pulses of methylprednisolone, low dose of corticosteroids and intravenous immunoglobulin, combined with antibiotics. Renal function dramatically improved in less than a week. At three months of follow-up, kidney function remains stable and ANCA serology negative. Conclusion In infective endocarditis, ANCA antibodies might have an important pathogenic role rather than secondary phenomena. We suggest that patients with IEAGN, that despite adequate antibiotic regimen present, present with kidney deterioration and evidence of crescentic glomerulonephritis on kidney biopsy, might require addition of immunosuppressives.

Diagnostic significance of antineutrophil cytoplasmic antibody (ANCA) titres: a retrospective case-control study

ObjectivesTo investigate the reliability of elevated titres of antineutrophil cytoplasmic antibody (ANCA) and to identify a cut-off titre in discriminating between ANCA-associated vasculitides (AAV) and its mimickers.MethodsThis retrospective observational single-centre...

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series

BackgroundRituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV.MethodsA total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively.ResultsThe baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group.ConclusionsThis is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.

Treatment of Recurrent Antineutrophil Cytoplasmic Antibody-Associated Vasculitis After Kidney Transplant With Rituximab: A Successful Case Report

Antineutrophil cytoplasm antibody-associated systemic vasculitis is a rare disease that frequently leads to end-stage renal disease. Kidney transplant should be delayed until patients are in complete clinical remission for at least 6 months, but the persistence of antineutrophil cytoplasmic antibody titers should not delay transplant. Recurrence of disease after kidney transplant is rare, with only a few cases described in the literature with heterogenous clinical manifestations, therapeutic approaches, and prognosis. We describe the case of a young male patient with recurrent antineutrophil cytoplasmic antibody vasculitis, 5 years after kidney transplant, successfully treated with methylprednisolone pulses plus rituximab. Rituximab presents a new valid option for the treatment of antineutrophil cytoplasmic antibody vasculitis relapse in kidney grafts.

Two pediatric cases with hematuria, normal renal function and positive antineutrophil cytoplasmic antibodies

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis requires prompt diagnosis and treatment, since renal function at the time of diagnosis is significantly associated with renal outcomes. Here, we report two pediatric patients with ANCA-positive glomerulonephritis initially presenting with hematuria, mild proteinuria, and normal renal function. The first patient with a high myeloperoxidase-ANCA titer (&gt;134 IU/mL) was diagnosed with rapidly progressive glomerulonephritis based on renal biopsy and treated with immunosuppressive therapy after 10 months of follow-up. The second patient with a low myeloperoxidase-ANCA titer (11 IU/mL) maintained normal kidney function without medication. Two cases showed different clinical course according to ANCA titer.

SEVERE IMMUNE-MEDIATED DIFFUSE ALVEOLAR HEMORRHAGE IN THE AGE OF COVID-19 AND EXTRACORPOREAL MEMBRANE OXYGENATION

SEVERE IMMUNE-MEDIATED DIFFUSE ALVEOLAR HEMORRHAGE IN THE AGE OF COVID-19 AND EXTRACORPOREAL MEMBRANE OXYGENATION

WITHDRAWN

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is an immune-mediated disease characterized by necrotizing vasculitis of the small blood vessels. Pulmonary involvement is common in AAV. Nodules and pleural effusions are the most common pulmonary finding in AAV. Fibrosing interstitial lung disease (ILD) is rarely associated with AAV, and it has a significant prognostication impact. We present a case of usual interstitial pneumonia (UIP) found in a patient with anti-Myloperoxidase (MPO) ANCA and rapidly progressive disease. CASE PRESENTATION: A 71-year-old female presented to the hospital with progressive exertional dyspnea and weakness for several months. Her physical exam was remarkable for bilateral basilar crackles. Oxygen saturation was 91% on ambient air. Chest radiograph showed lower zones interstitial infiltrates. Computed tomography of the chest showed diffuse reticular opacities in both lungs with honeycombing and traction bronchiectasis consistent with definite usual interstitial pneumonia (UIP) pattern. Laboratory evaluation revealed elevated serum creatinine (5.73 mg/dL). Immunology tests showed elevated anti-MPO ANCA titers. A renal biopsy showed the presence of pauci-immune crescentic glomerulonephritis, confirming the diagnosis of ANCA-mediated vasculitis. The patient was treated with plasmapheresis and 500 mg of intravenous methylprednisolone for three days, followed by cyclophosphamide and a medium dose of prednisone. Her kidney function improved, and she was then discharged to follow-up with pulmonary clinic for initiation of anti-fibrotic. DISCUSSION: ANCA-associated vasculitis (AAV) is a small-vessel vasculitis that can involve multiple organs. Pulmonary involvement has been reported in 25%–80% of cases. Sometimes, it can be the initial manifestation of the disease. The most common form of pulmonary involvement in AAV is diffuse pulmonary nodules, with or without cavitation and pleural effusions. Occasionally, patients can present with fibrosing-ILD, particularly with anti-MPO. This presentation is more prevalent in males and the elderly. Among AAV patients with ILD, UIP is the most frequent radiographic pattern. Non-specific interstitial pneumonia (NSIP) pattern can also be seen. ILD has been linked to increased mortality in AAV patients, particularly those with a UIP pattern. Treatment of fibrosing-ILD in AAV patients is not well established, with a questionable role for immunosuppression. Anti-fibrotic agents might be helpful in patients with a UIP pattern. CONCLUSIONS: UIP is rarely associated with AAV, and it can be the leading diagnostic manifestation. A careful clinical history and laboratory evaluation should be performed in patients with UIP to identify and treat any underlying systemic disease. UIP is a poor prognostic sign in AAV. Clinical trials are needed to establish the role of anti-fibrotic in treating this condition. Reference #1: Maillet T, Goletto T, Beltramo G, Dupuy H, Jouneau S, Borie R, Crestani B, Cottin V, Blockmans D, Lazaro E, Naccache JM, Pugnet G, Nunes H, de Menthon M, Devilliers H, Bonniaud P, Puéchal X, Mouthon L, Bonnotte B, Guillevin L, Terrier B, Samson M; French Vasculitis Study Group (FVSG). Usual interstitial pneumonia in ANCA-associated vasculitis: A poor prognostic factor. J Autoimmun. 2020 Jan;106:102338. doi: 10.1016/j.jaut.2019.102338. Epub 2019 Sep 27. PMID: 31570253. Reference #2: Mohammad AJ, Mortensen KH, Babar J, Smith R, Jones RB, Nakagomi D, Sivasothy P, Jayne DRW. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017 Oct;44(10):1458-1467. doi: 10.3899/jrheum.161224. Epub 2017 Aug 1. PMID: 28765242. Reference #3: Zhou P, Ma J, Wang G. Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis. Chron Respir Dis. 2021 Jan-Dec;18:1479973121994562. doi: 10.1177/1479973121994562. PMID: 33605150; PMCID: PMC7897823. DISCLOSURES: No relevant relationships by Mais Abdou No relevant relationships by Khaled Alshabani

Acute Cholecystitis in an Elderly Patient With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Report

A diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is difficult to establish in elderly patients. Herein, we report a case of acute cholecystitis mimicking sepsis in an elderly patient with ANCA-associated vasculitis. A 99-year-old woman was transferred to a rural community hospital on account of anorexia and hypotension; there, she was initially diagnosed with sepsis and treated accordingly. However, she developed new-onset right upper quadrant tenderness on indirect fist percussion of the liver, and Murphy’s sign was positive. While imaging did not reveal any findings suggestive of cholecystitis, the high index of suspicion for cholecystitis prompted an exploratory laparoscopy. Intraoperatively, the gallbladder wall was found to be inflamed, necessitating laparoscopic cholecystectomy. Histopathologic examination of the resected gallbladder showed neutrophilic infiltration and fibrinoid necrosis of the arterial walls. Perinuclear ANCA titers were elevated. These findings were consistent with a diagnosis of ANCA-associated vasculitis, and treatment with prednisolone markedly improved her condition. This case shows the difficulty encountered in differentiating between sepsis and ANCA-related vasculitis based on clinical features and relatively non-invasive diagnostic strategies alone. This study highlights the utility of invasive diagnostic procedures (e.g., biopsy) in elderly patients in whom a diagnosis of ANCA-associated vasculitis is difficult to establish.

Granulomatosis with polyangiitis: The trigger cannot be long hidden.

Granulomatosis with polyangiitis, or GPA, is a form of vasculitis that affects multiple organs especially the respiratory tract and the kidneys. The diagnosis is suspected with the clinical presentation and elevated serum titer of antineutrophil cytoplasmic antibodies and confirmed with the biopsy of the affected organ. Viral infection has been described as one of the triggers of the immune system in developing GPA. In this report, we describe a rare case of GPA that developed following cytomegalovirus infection in a patient with unknown immunocompromised medical condition.