Anti-neutrophil Cytoplasmic Antibody Serology Research Articles

Kidney involvement in myelodysplastic syndromes.

The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9g/g, and median serum creatinine was 3.2mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

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.

The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern wasnot associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. IV Laryngoscope, 134:2609-2616, 2024.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

Measurement of superoxide dismutase: clinical usefulness for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

ObjectiveTo investigate the clinical usefulness of serum superoxide dismutase (SOD) measurement in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsIn this single-center retrospective study, demographic data, serum SOD levels, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), the Birmingham Vasculitis Activity Score (BVAS), ANCA, organ involvement, and outcomes were analyzed for 152 AAV patients hospitalized in the Second Affiliated Hospital of Chongqing Medical University. Meanwhile, the serum SOD levels of 150 healthy people were collected as the control group.ResultsCompared to the healthy control group, serum SOD levels of the AAV group were significantly lower (P < 0.001). SOD levels of AAV patients were negatively correlated to ESR, CRP, and BVAS (ESR rho = − 0.367, P < 0.001; CRP rho = − 0.590, P < 0.001; BVAS rho = − 0.488, P < 0.001). SOD levels for the MPO-ANCA group were significantly lower than the PR3-ANCA group (P = 0.045). SOD levels for the pulmonary involvement group and the renal involvement group were significantly lower than those for the non-pulmonary involvement group and the non-renal involvement group (P = 0.006; P < 0.001, respectively). SOD levels in the death group were significantly lower than the survival group (P = 0.001).ConclusionsIn AAV patients, low SOD levels might indicate disease associated oxidative stress. SOD levels in AAV patients were decreased with inflammation, suggesting that SOD levels could potentially be a surrogate marker for disease activity. SOD levels in AAV patients were closely related to ANCA serology, pulmonary involvement, and renal involvement, with low SOD levels an important indicator of a poor prognosis for AAV patients.

#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.

MO051: Single-Cell Transcriptomics of Lupus Nephritis with ANCA Positive

Abstract BACKGROUND AND AIMS Lupus nephritis (LN) is one of the most common complications of SLE that can lead to worsened kidney function or renal failure. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies that are against antigens in the cytoplasm of neutrophils and monocytes and can lead to an autoimmune disease characterized by vascular necrotizing inflammation. The presence of ANCA in serum can also be found in SLE. Positive ANCA serology in patients with LN is associated with distinct histopathologic features on renal biopsy and seems to affect outcome of LN. Deeper understanding of the molecular pathogenesis in LN with ANCA positive is needed to identify novel targets improve the outcome of LN. METHOD Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from one LN patient with PR3-ANCA positive and a healthy adult kidney. We identified distinct cell clusters through unsupervised clustering analysis. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. RESULTS Unsupervised clustering analysis identified 15 distinct cell types including all of the renal intrinsic cells and major immune cells. The DEGs in kidney endothelial cells and intercalated cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling and Th17 cell differentiation. Macrophages displayed increased expression of HLA-DRB5, which plays a central role in the immune system by presenting peptides derived from extracellular proteins. TYROBP, a gene plays a role in signal transduction and inflammation, was also high-expressed in macrophages from kidney of LN with PR3-ANCA positive. The receptor-ligand crosstalk analysis highlighted the interactions between endothelial cells and other cells in LN, which infers great importance in LN. CONCLUSION We provide a searchable resource of single-cell RNA sequencing to LN with PR3-ANCA positive to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis and offer new insight into therapeutic targets of this unique type of LN.

Lung biopsy in the diagnosis of pediatric ANCA-associated vasculitis.

To investigate pulmonary histopathologic features in a cohort of pediatric patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) who underwent a lung biopsy as part of their evaluation. We report the safety and the findings of lung biopsies in this population. After IRB approval, we performed a retrospective chart review of all patients <18 years of age presenting to our institution with a diagnosis of pediatric AAV (pAAV) who underwent lung biopsy. We reviewed histopathologic features, serologies, the timing of biopsy, and complications. Fourteenpatients met inclusion criteria, nine patients with microscopic polyangiitis (MPA), and five patients with granulomatosis with polyangiitis (GPA). All patients had positive ANCA serology. 13/14 patients required admission on initial presentation for respiratory symptoms; 11/13 required respiratory support. The indication for biopsy was confirmation of diagnosis before initiating therapy in 11 patients (78%), part of the infectious evaluation in two (14%), and part of interstitial lung disease evaluation in one (7%). 11/14 (78%) biopsies had findings consistent with AAV diagnosis: 6/9 (67%) of the MPA patients compared with 5/5 (100%) of the GPA patients. The most common findings on histopathology were vascular inflammation and signs of alveolar hemorrhage. The only reported complication after lung biopsy was pneumothorax in four patients (28%). Lung biopsy had a higher diagnostic yield in GPA compared with MPA patients. In our cohort, a diagnosis of AAV could be made with clinical features and positive serology but was confirmed by lung histopathology in the majority of cases. Obtaining a lung biopsy for diagnostic purposes in pAAV should be reserved for uncertain cases where the diagnosis cannot be confirmed clinically and with serology.

P0374TREATMENT EFFICACY OF BIOSIMILAR RITUXIMAB (TRUXIMA) COMPARED TO THE ORIGINATOR (MABTHERA) IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Abstract Background and Aims Truxima is a biosimilar version of rituximab. It was licensed &amp; launched in the United Kingdom in April 2017. A biosimilar medicine is made to be highly similar in quality, safety and efficacy to existing licensed “reference” biological medicine and the cost is often significantly lower. A recent systematic review showed comparable long-term efficacy and safety of biosimilar rituximab to the originator drug in treatment of rheumatoid arthritis and non-hodgkin’s lymphoma. Fewer data are available in regards to the efficacy of biosimilar rituximab in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A retrospective study was thus conducted in our centre to examine the efficacy of Truxima when compared to the reference rituximab (MabThera) in the treatment of patients with AAV. Method All patients with new or relapsing AAV who received first ever rituximab therapy between 1/1/2016 and 31/12/2018 were identified via hospital dispensing database. Patients were stratified into Truxima or MabThera treatment group depending on the version of rituximab administered. Primary outcomes that were assessed include: time to B cell depletion (defined as absolute B cell count (ABC) ≤10) and repletion (i.e ABC &amp;gt;10 and &amp;gt;20); time to antimyeloperoxidase(MPO)/antiproteinase 3(PR3)-ANCA negativity; Secondary outcomes assessed include: overall survival, time to major relapse (defined as relapse requiring further course of rituximab for remission induction); adverse events including episodes of neutropenia, hypogammaglobulinemia and major infusion reactions. Subgroup analysis in patients who received concomitant cyclophosphamide and rituximab or other induction therapy was performed to examine if it impacts on the treatment efficacy. Results 59 and 60 patients received Truxima and MabThera respectively for treatment of new or relapsing AAV. The baseline characteristic (age, gender, entry estimated Glomerular Filtration Rate, proportion of patients received concomitant cyclophosphamide, ANCA serology and organ involvement) of both group were comparable. All patients achieved clinical remission following induction treatment. Using Kaplan Meier analysis and log rank test, no difference was identified in time to B cell depletion or repletion (Figure 1&amp;2), MPO/PR3-ANCA negativity (Figure 3), overall survival or major relapses requiring further rituximab as induction therapy. Treatment efficacy of Truxima and MabThera did not differ in subgroup analysis. However we observed that patients who received concurrent cyclophosphamide during induction therapy achieved MPO/PR3-ANCA negativity more rapidly compared to those who did not irrespective of the version of rituximab received. No difference in adverse events such as major infusion reactions was seen in either group upon first rituximab exposure. Two patients in each group developed reactions following repeated dosing of rituximab. Conclusion Biosimilar rituximab Truxima appears to have comparable treatment efficacy compared to the reference drug in our cohort of patients with AAV.

Antineutrophil cytoplasmic antibodies (ANCA) - their role in pathogenesis, diagnosis, and treatment monitoring of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCA. Increasing clinical and experimental evidences support their pathogenic role in AAV, but the exact mechanism is not fully understood. Recently, the important role of neutrophil extracellular traps (NETs) in pathogenesis of AAV is underlined. There is an indication that NETs can be a source for the formation of ANCA. The most common ANCA target antigens are myeloperoxidase (MPO) and proteinase 3 (PR3). Though the mechanism of action of ANCA is still under exploration, ANCA serology is being increasingly used for classification of AAV and revealed as kenner in defining various disease subsets associated with different genetic background, clinical features, treatment response, and prognosis. Controversy exists regarding the utility of serial measurements of ANCA in patients with AAV to monitor treatment and predict disease relapse.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. Objective: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. Method: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca’ Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. Results: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. Conclusion: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Peroxidasin Is a Novel Target of Autoantibodies in Lupus Nephritis

Peroxidasin Is a Novel Target of Autoantibodies in Lupus Nephritis

Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance

Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response. The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n=536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. During VDZ induction, at week 6, inflammatory bowel disease patients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P=0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval=0.567-0.878, P=0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P=0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P=0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction.

Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are very rare in childhood with an increased risk of morbidity and mortality. We aimed to evaluate renal prognostic factors in childhood AAV from the perspective of ANCA serotype, histopathological classification, and five-factor score (FFS). Pediatric AAV patients from 11 referral centers in Turkey had been included to the study. The demographics, clinical findings, AAV subtypes, outcomes, and FFS were evaluated retrospectively. Kidney biopsies were classified histopathologically. Totally, 39 patients were enrolled in the study. Among all patients, 74.4% had renal involvement, 56.4% ear-throat-nose involvement, and 51.3% had musculoskeletal involvement. Proteinase 3 (PR3)-ANCA was positive in 48.7%, and myeloperoxidase (MPO)-ANCA was positive in 30.8%. 69.2% of patients had impaired renal function, and 28.2% had progressed to end-stage renal disease (ESRD) during the follow-up. At the time of diagnosis, FFS was ≥ 2 in 53.8%. The most common histopathologic classifications were as follows: crescentic type in 40.7% and sclerotic type in 25.9%. Gastrointestinal and renal involvement, MPO-ANCA positivity, serum creatinine levels, and impaired renal function during the follow-up were significantly higher in patients with FFS ≥ 2, compared to patients with FFS < 2. Patients with FFS ≥ 2 had more common crescentic, mixed and sclerotic histopathologic findings in biopsies. By logistic regression analysis forward method, the strongest single-risk factor among all the parameters was the initial level of creatinine in patients with ESRD, compared to the other patients (p = 0,007). Evaluation of the FFS, ANCA serology, and the creatinine levels may help to predict renal prognosis.

Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis: a case series of 15 patients

Objective: We aimed to describe the clinical characteristics and treatment course of hypertrophic pachymeningitis (HPM) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods: We retrospectively analysed 15 patients (11 men and four women). HPM was diagnosed based on thickening and enhancing of the brain and/or spinal dura mater on gadolinium-enhanced magnetic resonance imaging (MRI) T1 sequence.Results: The median age at HPM onset was 60 years. Headache and cranial nerve impairment were observed in 14 and 10 patients, respectively. Otitis media and/or mastoiditis were found as complications of AAV in 11 patients. Fourteen patients were classified as having granulomatosis with polyangiitis (GPA). Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, and double-positive ANCA were identified in seven patients, five patients, and one patient, respectively. With MRI, thickening of the dura mater in the cranial fossa and tentorium cerebelli was found in 10 and eight patients, respectively. For remission induction, all patients were treated with corticosteroids, and immunosuppressants were added in 10 patients. Dura mater thickening partially improved in all patients, and cranial neuropathy completely remitted in eight patients. In a median follow-up of 43 months, four patients had HPM relapse and underwent reinduction therapy. All six patients treated with cyclophosphamide at initial therapy did not relapse.Conclusions: HPM was mostly associated with patients with GPA with otitis media and/or mastoiditis having either type of ANCA serology. Treatment with corticosteroids with or without immunosuppressants was effective. However, HPM relapse occasionally occurred, especially when cyclophosphamide was not used in initial treatment.

An evaluation of the 2010 histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis: a Bayesian network meta-analysis

In 2010, a new histopathological classification of ANCA-associated glomerulonephritis (ANCA-GN) based on four categories (focal, crescentic, mixed, and sclerotic) was proposed to predict renal outcome. However, this classification was the source of much debate in different populations. We aimed to evaluate this classification scheme in terms of renal survival using Bayesian network meta-analysis. We searched Pubmed, Embase, and Medline for articles published between 1 October 2010 and 9 August 2017 that assessed the predictive value of this classification. We pooled hazard ratios (HRs) for end-stage kidney disease (ESRD) among the four categories using a Bayesian random-effects model. Clinical factors that could potentially influence renal outcome among the different trials were explored by meta-regression. Sixteen case-controlled studies, including a total of 1945 patients with 1695 endpoint events, were included. Compared with sclerotic, the HRs for ESRD were 0.45 [95% confidence interval (CI) 0.26-0.79] for crescentic, 0.34 (0.22-0.51) for mixed, and 0.24 (0.12-0.51) for focal. Pooled results showed no obvious difference between the crescentic and the mixed sub-groups (HR 1.35; 95% CI 0.90-2.0). Baseline eGFR (P = 0.002) and the ANCA serology (P = 0.029) were associated with renal survival. The 2010 ANCA-GN classification and the extent of ANCA serology and baseline eGFR were shown to be significant predictors of renal outcome, although there was no significant prognostic difference between crescentic and mixed. The ANCA-GN classification scheme should, therefore, be optimized by combining with other established parameters, such as tubular atrophy and the proportion of normal glomeruli.

Prognosis and Histological Classification in Elderly Patients with ANCA-Glomerulonephritis: A Registry-Based Cohort Study.

Background The value of a histologic classification scheme to classify patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into focal, mixed, crescentic, and sclerotic types for predicting risk of end-stage renal disease (ESRD) is well documented. However, the prognostic value of histological classification specifically in elderly patients (≥70 years) with ANCA-GN has not previously been investigated. Methods Patients with biopsy-verified pauci-immune necrotizing glomerulonephritis were identified from the Norwegian Kidney Biopsy Registry between 1991 and 2012 and those ≥70 years of age at the time of diagnosis and having positive anti-neutrophil cytoplasmic antibody serology were included in this study. The incidence rate of ESRD and/or death was determined by linking the study cohort to the Norwegian Renal Registry and the Population Registry of Norway. The ESRD-free survival and patient survival were compared between the 4 histological types. Results Of the 81 patients included, 20 progressed to ESRD and 34 died. The 1-year and 5-year ESRD-free survival varied between histological groups (p = 0.003) as follows: focal, 97% and 97%, respectively; mixed, 70% and 57%; crescentic, 76% and 63%; and sclerotic, 49% and 49%. Patient survival did not differ significantly between groups (p = 0.30). Conclusion Histological classification in elderly patients with ANCA-GN is useful for predicting ESRD but not survival.

Impact of Proteinase 3 versus Myeloperoxidase Positivity on Risk of End-Stage Renal Disease in ANCA-Associated Glomerulonephritis Stratified by Histological Classification: A Population-Based Cohort Study.

Background End-stage renal disease (ESRD) risk in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis (ANCA-GN) according to ANCA serotype and stratified by histological classification has not been previously investigated. Methods Patients from the Norwegian Kidney Biopsy Registry (NKBR) between 1991 and 2012 who had biopsy-verified pauci-immune glomerulonephritis and positive antineutrophil cytoplasmic antibody serology were included. Cases with ESRD during follow-up were identified in the Norwegian Renal Registry. ESRD-free survival with proteinase 3 (PR3) versus myeloperoxidase- (MPO-) ANCA positivity stratified into 4 histological classes was investigated. Results Three hundred fifty-eight patients, of whom 87 progressed to ESRD during follow-up, were included. Patients with PR3- as compared to MPO-ANCA were younger (58 versus 64 years, p = 0.001), had a higher percentage of males (62 versus 41%, p < 0.001), had a lower percentage with a sclerozing glomerulonephritis pattern (4 versus 16%, p < 0.001), and had a significantly higher cumulative ESRD-free survival (90 versus 80%, p = 0.007) at 1-year follow-up. No significant differences in cumulative ESRD-free survival with PR3- as compared to MPO-ANCA were observed by histological stratification. Conclusion Advanced glomerular sclerosis is found more frequently in patients with MPO-ANCA, explaining the higher risk of ESRD. ANCA serotypes have no impact on prognosis of patients with similar histological findings.

Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy

Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative biopsies from patients with lupus nephritis. The majority (82%) of ANCA-positive patients had antimyeloperoxidase antibodies. Class IV-S lupus nephritis and glomerular necrosis were significantly more common (36% vs. 16% and 35% vs. 15%, respectively) and isolated Class V lupus nephritis significantly less common (10% vs. 29%) in the ANCA-positive group. ANCA-positive patients had significantly higher dsDNA titers (335u/ml vs. 52u/ml), significantly lower serum C4 concentrations (0.125g/L vs. 0.15g/L) and significantly higher serum creatinine (130μmol/L vs. 84μmol/L) at the time of biopsy. Hence ANCAs appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology. There was no significant difference in outcome between groups when matched for severity of disease and treatment using propensity scoring. Thus, further studies are needed to examine whether ANCAs in patients with lupus nephritis have a pathogenic role and whether they are associated with worse renal outcomes or are simply a marker of more severe disease.

Cutaneous Manifestations of ANCA-Associated Small Vessels Vasculitis.

Skin lesions are frequent manifestations of underlying systemic conditions, including systemic autoimmune vasculitis. In particular, anti-neutrophil cytoplasmic antibodies (ANCA) are associated with distinct forms of vasculitis characterized by inflammatory cell infiltration of the walls of small and medium-sized vessels leading to vascular destruction and tissue necrosis. ANCA-associated vasculitis is rare and systemic diseases, which can be classified based on different distribution of vascular inflammation and presence or absence of granulomatosis and asthma. Despite their diversities, ANCA-associated vasculitis, namely microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, can all display a broad variety of cutaneous manifestations, which can appear during the course of the disease or even as first sign at the time of onset. Different skin manifestations might coexist in the same patient and occur in different occasions during the course of the vasculitis. Thus, a deep knowledge of the spectrum of skin lesions as part of ANCA-associated vasculitis is mandatory for a correct diagnostic process, whenever cutaneous vasculitis is suspected. Due to this broad variety of manifestations, the diagnosis of skin involvement in ANCA-associated vasculitis is very challenging and it must be supported by a detailed medical history, accurate physical examination, specific histopathological analysis of skin biopsy and the presence of ANCA serology. In this review, we focus on the cutaneous manifestations that can develop in the context of ANCA-associated vasculitis, detailing the clinical features, the histopathological aspects as well as the direct immunofluorescence studies for each of the three conditions. Moreover, we acknowledged the differential diagnoses that must be ruled out in the diagnostic process and the main therapeutic approaches available for treatment of ANCA-associated vasculitis.