Presence Of Antineutrophil Cytoplasmic Antibodies Research Articles

Granulomatosis with polyangiitis and facial palsy: Literature review and insight in the autoimmune pathogenesis.

Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported. Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve 'vasa nervorum' is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported. GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations.

Anti-CD20 therapy and pauci-immune crescentic glomerulonephritis.

Pauci-immune glomerulonephritis represents an important cause of crescentic glomerulonephritis, which may be renal-limited vasculitis or part of systemic vasculitis, i.e., microscopic polyangiitis, granulomatosis with polyangiitis (previously known as Wegner’s granulomatosis) and eosinophilic granulomatosis with polyangiitis (previously known as ChurgeStrauss Syndrome). While the presence of antineutrophil cytoplasmic antibody (ANCA) serves a diagnostic tool and leads to the term “ANCA-associated vasculitis,” these autoantibodies are also involved in the pathogenesis. Moreover, there are reports of a positive correlation between B cell activation status and disease activity and the central role of B cells is further supported by reports mentioning that the cyclophosphamide effect is mediated through the suppression of B-cell functions. Thus, suppression of antibody production by Bcell depleting agents to reduce ANCA levels becomes appealing. The murine-human chimeric anti-CD20 monoclonal antibody rituximab depletes B cells and suppresses the production of antibodies. Moreover, rituximab affects other B cell-mediated processes, including but not limited to antigen presentation, cytokine production, and B cell:T cell costimulation, and was associated with the expansion of

The pathogenesis of ANCA-associated vasculitis.

ANCA-associated vasculitis is characterized by the presence of anti-neutrophil cytoplasmic antibody (ANCA) in the serum. ANCA is a pathogenic autoantibody as well as the disease marker. It has been realized that ANCA-cytokine sequence is involved in the pathogenesis of ANCA-associated vasculitis. Recent studies have revealed that neutrophil extracellular traps induced by ANCA are also involved in the pathogenesis. In this study, we review the roles of neutrophils, eosinophils, macrophages/dendritic cells, complements, B cells/plasma cells, T cells, and cytokines/chemokines/cell growth factors in the pathogenesis of ANCA-associated vasculitis.

The Clinicopathologic Spectrum of Rapidly Progressive Glomerulonephritis Based on Glomerular Immune Deposition and Antineutrophil Cytoplasmic Antibody

Rapidly progressive glomerulonephritis presents crescentic glomerulonephritis (CrGN) pathologically. Immune complex (IC)-mediated CrGN is characterized by glomerular IC deposits, whereas pauci-immune CrGN is characterized by presence of antineutrophil cytoplasmic antibody (ANCA) and absence of glomerular IC deposits. CrGN cases presenting both IC deposits and ANCA were common. We retrospectively investigated 91patients with rapidly progressive glomerulonephritis, including 36 patients with idiopathic IC-mediated CrGN and 55 patients with pauci-immune CrGN. On the basis of ANCA and IC deposits, there were 42 patients with ANCA alone (ANCA+IC-), 6 patients with IC deposits alone (ANCA-IC+), 30 patients with both ANCA and IC deposits (ANCA+IC+), and 13 patients with neither ANCA nor IC deposits. The patients with IC-mediated CrGN had more proteinuria, lower estimated glomerular filtration rate (eGFR), higher percentage of cellular crescent formation, and a worse renal outcome compared with those with pauci-immune CrGN. The ANCA+IC+ CrGN patients had lower eGFR level, higher percentage of crescent formation and a tendency of more proteinuria, and worse renal outcome compared with ANCA+IC- CrGN patients, but had no significant differences on the above characteristics compared with ANCA-IC+ CrGN patients. Within a median 7.1 months, 22 patients developed end-stage renal disease. Cox regression revealed the factors including lower eGFR level, more proteinuria, lower platelet level, higher glomerular global sclerosis rate, and glomerular IgG deposits were the independent factors for worse renal outcome. In conclusion, the clinicopathologic spectrum of ANCA+IC+ CrGN was similar with IC-mediated CrGN and glomerular IgG deposition was one of the independent factors for worse renal outcome.

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.

Current therapies for ANCA-associated vasculitis.

The ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA, formerly Wegener's), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss), are a group of multisystem autoimmune diseases characterized by necrotizing small- to medium-vessel vasculitis and the presence of anti-neutrophil cytoplasmic antibodies. Current therapeutic strategies consist of glucocorticoids in conjunction with either conventional or biologic agents for both induction of remission and remission maintenance. Treatment goals include reducing toxicity of induction therapy, preventing disease relapse, and limiting overall accrual of both disease-related damage and treatment-related morbidity. Future research directions include investigation of the optimal duration and frequency of maintenance therapy as well as development of targeted therapeutic agents, which is enhanced by emerging insights into disease pathogenesis.

Antineutrophil Cytoplasm Antibody: Positivity and Clinical Correlation

ObjectiveTo determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). Material and methodsA prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. ResultsMost positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ConclusionANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.

Anticuerpos contra el citoplasma del neutrófilo: positividad y correlación clínica

ObjectiveTo determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). Material and methodsA prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. ResultsMost positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ConclusionANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.

AB0534 Does the Presence of ANCA in Patients with Lupus Nephritis (LN) Help to Distinguish A Subset?

BackgroundAntineutrophil cytoplasm antibodies (ANCA) are known to occur in some patients with systemic lupus erythematosus (SLE), with a prevalence of 15 to 20% [1]. The perinuclear pattern (pANCA) predominates in...

Cocaine induced midline destructive lesions.

Review of the literature concerning cocaine induced midline destructive lesions (CIMDL). We reviewed the English literature regarding CIMDL involving the nose and its surrounding structures. The review is based on a search of the US National Library of Medicine (PubMed) online database from January 1st, 1982 to March 31st, 2013. CIMDL is a pathology that mimics systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA). The prevalence of CIMDL is considered to be about 4.8% among cocaine users. Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal septal perforation, palatal perforation, sinus wall destruction, orbital erosion and damage of the anterior skull base. The presence of ANCA directed against human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL. Toxicological tests, indirect immunofluorescence microscopy, antigen specific solid assay testing, histopathological analysis, apoptosis assay and MRI imaging concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is poorly understood and implicates inflammatory, infective, proapoptotic and autoimmune mechanisms. CIMDL must be readily recognized by clinicians to provide appropriate treatment. Immunosuppressive therapy has no role in the treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

Anti-PR3 and anti-MPO antibodies are not present in sera of patients with pulmonary tuberculosis

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed to intracellular components of neutrophils and are present in several vasculitic syndromes. Recently, these autoantibodies have been described in other autoimmune disorders as well as in infectious diseases such as tuberculosis (TB). As there are some clinical similarities between TB and granulomatosis with polyangiitis, we searched for ANCA in a group of patients with proven TB. Patients with TB confirmed by chest X-ray and sputum bacilloscopy either before or within 30 days after beginning treatment were included in this study. Anti-MPO and anti-PR3 antibodies were studied using well-standardized ELISA kits (INOVA Diagnostics, Inc.). ANCA were also investigated by indirect immunofluorescence (IIF). Fifty TB patients (26 females, mean age 47.34 ± 17 years) were enrolled in the present study. No patient tested positive for ANCA by IIF, or anti-MPO or anti-PR3 antibodies by ELISA. Although previous studies have shown the presence of ANCA in some infectious diseases, the findings of the present study demonstrated the absence of such antibodies in TB. The discrepancy in the prevalence of ANCA in TB among different studies may be attributed to methodological factors and/or the genetic background of the studied populations.

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss)

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) is a peculiar hybrid condition of a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and a hypereosinophilic disorder with frequent lung involvement that occurs in people with asthma. This review focuses on areas of evidence or persistent uncertainty in the classification, epidemiology, clinical presentation, diagnosis, prognosis and management of EGPA and attempts to identify clues to the mechanisms in the development or course of the disease. The 2013 revision of the EGPA definition formally placed the disease in the subset of ANCA-associated vasculitides. Recently published large case series underlined that the presence of ANCAs, found in 30-40% of EGPA, determines distinct but partly overlapping disease expression and the major detrimental effect of heart involvement on survival. There is some evidence that asthma in EGPA resembles a nonallergic eosinophilic asthma phenotype. Encouraging results have been reported for the treatment of EGPA with rituximab or with the eosinophil-targeted antiinterleukin-5 agent mepolizumab. The understanding of EGPA continues to advance, but many gaps in knowledge remain. The nomenclature remains a source of conceptual variance in terms of demonstrated presence or not of vessel inflammation or ANCAs in the diagnosis of EGPA. Distinguishing EGPA from hypereosinophilic syndromes can be problematic, and an understanding of the mechanistic relation between the vasculitis and the eosinophilic proliferation is profoundly lacking. Some evidence suggests distinct disease phenotypes, but this concept has not yet been translated to phenotype-adapted therapy.

A Case of Antineutrophil Cytoplasmic Antibody-negative Granulomatosis with Polyangiitis Presenting as Breast Mass

Granulomatosis with polyangiitis (GPA) is a disease characterized by a granulomatous necrotizing vasculitis of the small vessels, along with the presence of antineutrophil cytoplasmic antibody (ANCA), serologically. GPA is a multisystem disease, in which the diagnosis is frequently based on respiratory and renal manifestations, with rare breast invasion. To date, several cases of breast invasion by GPA have been published, and most cases have been positive for ANCA. However, ANCA-negative forms of breast invasion by GPA are extremely rare and have not been reported in Korea thus far. Therefore, we report a case of ANCA-negative GPA in a 70-year-old woman, who was initially presented with a localized palpable mass in the left breast.

Cocaine induced midline destructive lesions

Review of the literature concerning cocaine induced midline destructive lesions (CIMDL). We reviewed the English literature regarding CIMDL involving the nose and its surrounding structures. The review is based on a search of the US National Library of Medicine (PubMed) online database from January 1st, 1982 to March 31st, 2013. CIMDL is a pathology that mimics systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA). The prevalence of CIMDL is considered to be about 4.8% among cocaine users. Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal septal perforation, palatal perforation, sinus wall destruction, orbital erosion and damage of the anterior skull base. The presence of ANCA directed against human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL. Toxicological tests, indirect immunofluorescence microscopy, antigen specific solid assay testing, histopathological analysis, apoptosis assay and MRI imaging concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is poorly understood and implicates inflammatory, infective, proapoptotic and autoimmune mechanisms. CIMDL must be readily recognized by clinicians to provide appropriate treatment. Immunosuppressive therapy has no role in the treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

Antineutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis

Objective.Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA may be detectable in bile, potentially providing diagnostic and prognostic information. Methods.Serum and bile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other non-PSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). Results.Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p = 0.004), number of ERC (p = 0.01) and interventions performed (p = 0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. Conclusions.The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications.

Antineutrophil cytoplasm antibody–associated vasculitis: recent developments

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment. A genome-wide association study has confirmed a role for genetic susceptibility in AAV, and links between environmental factors and AAV induction through abnormal neutrophil extracellular traps has been demonstrated. Ongoing international consensus initiatives have revised approaches to the classification of vasculitis that has been enhanced by the analysis of large-scale prospective clinical data sets. New autoantibodies to human lysosome-associated membrane protein-2 antibody, moesin, and plasminogen have been detected in AAV sera and a prognostic classification of renal biopsies developed. Clinical trial networks have extended the evidence base for the treatment of AAV, and rituximab has emerged as an alternative to cyclophosphamide for remission induction. Long-term outcomes following current treatment strategies have been determined and increased risks for cardiovascular and malignant disease reported.

Vascularite cutanée à anticorps anti-cytoplasme des polynucléaires neutrophiles induite par le benzylthio-uracile : à propos d’un cas et revue de la littérature

IntroductionVasculitis associated to antineutrophil cytoplasmic antibodies is a rare complication of therapy with antithyroid medication. They were mainly reported in patients treated with propylthiouracil and rarely with benzylthiouracil. Case reportWe report a 22-year-old woman treated with benzylthiouracil for Graves’ disease, who developed a vasculitic skin involvement. The presence of antineutrophil cytoplasmic antibodies with anti-myeloperoxidase specificity was documented. The discontinuation of benzylthiouracil was followed by a complete disappearance of skin lesions and of antineutrophil cytoplasmic antibodies. ConclusionTo our knowledge, only ten cases of antineutrophil cytoplasmic antibodies vasculitis induced by benzylthiouracil have been previously reported in the literature. Our patient was characterized by the occurrence of isolated cutaneous vasculitis, without renal involvement. Early discontinuation of benzylthiouracil may have prevented the occurrence of severe visceral complication.

Study about correlation of anti-neutrophil cytoplasmic antibodies and anticardiolipin antibodies with thromboangiitis obliterans

Doctors often have difficulties in clinical diagnosis and clinical stage of thromboangiitis obliterans (TAO). Immunolesion was important in the initiation and progression of various kinds of vasculitis diseases, including TAO. Several kinds of immune complexes were developed by immunolesion, including anti-neutrophil cytoplasmic antibodies (ANCA) and anticardiolipin antibodies (ACA). Our aim was to determine if it is an effective way for clinical diagnosis and clinical stage of TAO by detection of the presence of ANCA and ACA in blood serum of patients with TAO and the relationship among the presence of ANCA, ACA and patients with different grades of TAO. Blood samples and clinical characteristics were collected from 38 patients with Rutherford grade I TAO, 30 patients with Rutherford grade II–III TAO, 75 patients with arteriosclerosis obliterans (ASO) and 65 healthy volunteers. Their serum samples were investigated for ANCA by indirect immunofluorescent (IIF), and for ACA and ANCA specificity antigens including reactivity to proteinase 3(PR3), myeloperoxidase (MPO), cathepsin G (CG), bactericidal/permesbility-increasing protein (BPI), elastase (HLE) and lactoferrin (LF) by enzyme linked immunosorbent assay (ELISA). (1) ANCA positive rate and titre were much higher in cases with Rutherford grade I TAO (52.6%, 20/38, 0.386 ± 0.458) and Rutherford grade II–III TAO (73.3%, 22/30, 0.847 ± 0.658) than those in cases with ASO (4%, 3/75, 0.011 ± 0.002) and healthy volunteers (0%,0/65, 0.010 ± 0.002) (P < 0.01). ANCA positive rate and titre were higher in cases with Rutherford grade II–III TAO (73.3%, 22/30, 0.847 ± 0.658) than those in cases with Rutherford grade I TAO (52.6%, 20/38, 0.386 ± 0.458) (P < 0.05). (2) ACA concentration was much higher in cases with Rutherford grade I TAO (270.13 ± 13.05 IU/mL) and Rutherford grade II–III TAO (279.33 ± 19.98 IU/mL) than that in cases with ASO (236.85 ± 17.32 IU/mL) and healthy volunteers (229.16 ± 15.55 IU/mL) (P < 0.05) respectively. (3) In 42 cases of ANCA-positive samples, there were 20 cases reacted with MPO, 14 cases reacted with LF, five cases reacted with HLE, five cases reacted with BPI and no one reacted with PR3 and CG. All cases were Rutherford grade II–III TAO. Our results indicate that ANCA, ANCA specificity antigens and ACA were detected susceptibly and availably in patients with TAO. Thus, detection of ANCA, ANCA specificity antigens and ACA was helpful for clinical diagnosis of TAO and detection of ANCA and ANCA specificity antigens was helpful for clinical staging of TAO. They are important assistance for clinical diagnosis and stage of TAO.

High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis

Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p<0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p<0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p<0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18-2.56, p=0.006). Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents.

Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody

A subset of patients with crescentic glomerulonephritis (CGN) is characterized serologically by the presence of antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM) called "double positive" disease. The clinical significance of the occurrence of both antibodies is not clear. This study aims to describe the clinical and histologic characteristics and outcomes of CGN in a US cohort of double positive (DP) patients and compare them to patients with anti-GBM disease only or ANCA only (ANCA-associated vasculitis (AAV)). Renal biopsies with a diagnosis of CGN with either pauci-immune or linear immunofluorescence were selected and classified as AAV, anti-GBM disease, or DP based on serologic testing at the time of biopsy. Data on demographics, clinical presentation, treatment, and outcome were obtained by chart review. Six patients with anti-GBM disease, 9 with DP disease, and 18 AAV patients matched for year of diagnosis with DP were identified. Extrarenal disease manifestations were more prominent in the DP patients. The DP patients had severe renal dysfunction at presentation with eight of nine patients requiring dialysis at presentation. Renal biopsy findings of DP patients were similar to anti-GBM disease with majority of glomeruli showing cellular crescents. Eighty-nine percent of patients were treated with immunosuppressive therapy and 78% with plasmapheresis. At 1year, all nine DP patients reached end-stage renal disease. We conclude that the DP patients share extrarenal manifestations similar to AAV patients while the renal manifestations resemble anti-GBM patients clinically and histologically. The renal prognosis of DP patients remains poor despite treatment.