Anti-Glomerular Basement Membrane Disease without Linear IgG Deposits in an Elderly Patient with Metastatic Rectal Cancer: A Case Report

Eculizumab and Complement Activation in Anti−glomerular Basement Membrane Disease

The Uncertain Significance of Anti–Glomerular Basement Membrane Antibody Among HIV-Infected Persons With Kidney Disease

Atypical Antiglomerular Basement Membrane Nephritis Following Immune Checkpoint Inhibitor

SAT-397 PAUCI-IMMUNE VASCULITIS - CLINICAL CHARACTERISTICS AND OUTCOME ANALYSIS OF 120 PATIENTS FROM A SINGLE CENTER IN INDIA

IntroductionGoodpasture's syndrome consists of a triad of pulmonary hemorrhage, rapidly progressive glomerulonephritis and anti-glomerular basement membrane (anti-GBM) antibodies, either in circulation or fixed to the kidney. The absence of renal manifestations is uncommon. We present a case of biopsy proven anti-GBM antibody disease with normal renal function, mild urinary abnormalities and positive C-antineutrophil cytoplasmic antibody (C-ANCA) serology.Case presentationA 44-year-old female was treated for repeated episodes of hemoptysis and one episode of respiratory failure requiring ventilatory support. She had minor urinary abnormalities in the form of microscopic hematuria and non-nephrotic proteinuria. She also had positive C-ANCA. Her lung biopsy showed evidence of intra-alveolar hemorrhage with linear IgG deposits in the basement membrane of the alveolar capillaries. Owing to these lung biopsy findings, a kidney biopsy was carried out, which showed minimal thickening of the glomerular basement membrane and linear IgG and C3 deposits along the capillary walls. Her renal function remained persistently normal.ConclusionGoodpasture's syndrome is a rare disease. Even though the classical presentation is that of rapidly progressive glomerulonephritis pulmonary hemorrhage and anti-GBM antibodies in the circulation and kidneys, in rare cases it can present with repeated pulmonary hemorrhage and minor urinary abnormalities. In all cases of repeated pulmonary hemorrhage, the possibility of Goodpasture's syndrome should be considered and investigated further.

Concurrent anti-GBM disease and IgA glomerulonephritis

Anti-glomerular basement membrane (anti-GBM) disease is a systemic autoimmune disorder characterized by circulating immunoglobulin (Ig) G antibodies to carboxy-terminal, noncollagenous 1 domain of type IV collagen of GBM. Patients typically present with rapidly progressive glomerulonephritis and pulmonary hemorrhage. Anti-GBM disease has been reported to coexist with pauci-immune antineutrophil cytoplasmic autoantibody-positive glomerulonephritis and membranous glomerulopathy. The presentation of anti-GBM disease with thrombotic microangiopathy (TMA) and IgA nephropathy has been rarely described. We herein report two cases of anti-GBM antibody disease, both with crescentic glomerulonephritis and peripheral linear deposits of IgG, one case with clinical and histological findings of associated TMA and other with findings of extensive mesangial IgA deposits. Both the patients were treated with corticosteroid, intravenous cyclophosphamide, and plasma exchange but had poor renal recovery. Association of anti-GBM disease with TMA or IgA nephropathy could open up new pathogenetic mechanism and may help us to prognosticate anti-GBM disease.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is characterized by rapidly progressive glomerular nephritis with or without pulmonary hemorrhage with disease severity correlating with antibody titer. Following treatment, relapse is rare but has been reported in the literature. The objective of this study was to assess for clinical, serologic, and histologic differences associated with disease relapse in patients with anti-GBM disease. Methods: Patients seen at our facility between 1997 and 2017 were screened for anti-GBM disease by ICD 9/10 codes. They were included if the diagnosis was confirmed by a board-certified rheumatologist or nephrologist and had positive antibodies and/or biopsy results consistent with anti-GBM disease. Relapsing disease was defined as recurrence of pulmonary or renal manifestations after achieving remission following the initial presentation. All charts were reviewed for baseline demographics, clinical manifestations, and antibody positivity and compared between groups. Results: 40 patients were confirmed as having anti-GBM disease. Mean follow-up from disease onset to the date of last follow-up was 56.2 months. 8 patients had relapsing disease and 32 patients had nonrelapsing disease. Baseline characteristics and clinical manifestations were similar between groups. Patients with relapsing disease had a high incidence of anti-neutrophilic cytoplasmic antibody (ANCA) co-positivity as compared to nonrelapsing patients (50 vs. 15.6%, respectively, p = 0.059), but this did not reach statistical significance. In patients with relapsing disease, only one had positive anti-GBM antibodies at time of relapse. Conclusions: In this study, patients with relapsing disease had a high incidence of ANCA co-positivity (50%). In patients with newly diagnosed anti-GBM disease, ANCAs should be obtained to assess for the risk of relapse and to help guide long-term follow-up and treatment.

BackgroundRenal injury of anti-glomerular basement membrane (GBM) disease is defined by the linear deposition of IgG along GBM and rapidly progressive glomerulonephritis. To date, the distribution of anti-GBM IgG subclasses on renal tissue is still unclear. In the current study, we investigated the deposition of the four IgG subclasses using immunohistochemistry in the renal biopsy specimens from 46 patients with anti-GBM disease.ResultsAll four IgG subclasses can be detected within the GBM. Anti-GBM IgG3 was detected in all patients (100%), with 39 (84.8%) patients presenting with weak segmental staining and 7 (15.2%) patients with strong linear deposition. Anti-GBM IgG2 was detected in 22 (47.8%) patients, with 20 (90.9%) patients having weak segmental deposition and 2 (9.1%) patients presenting strong linear staining. Anti-GBM IgG1 and IgG4 were detected in 9 (19.6%) and 7 (15.2%) patients, respectively. IgG deposition along tubular basement membrane (TBM) was also detected in 31 (67.4%) patients. Among them, the IgG subclass distribution was similar to that of the deposition within the GBM: IgG1 6.5% (2/31), IgG2 45.2% (14/31), IgG3 100% (31/31) and IgG4 9.7% (3/31). We observed increased inflammatory cell infiltration into the interstitium in patients with increased anti-TBM IgG3 deposits (P=0.031).ConclusionsAnti-GBM IgG3 predominantly deposits along GBM and TBM on renal biopsy specimens from patients with anti-GBM disease, which may be involved in the development of renal injury of the disease.

Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune kidney disease in which autoantibodies are directed against GBM components. Type IV collagen and laminin α5β2γ1 (laminin 521) within the GBM are two major target antigens in anti-GBM disease. Perlecan is a type of heparan sulphate proteoglycans, ubiquitously expressed in basement membranes. The present study aimed to investigate whether perlecan could be recognized by anti-GBM antibodies and further analysed the properties and clinical associations of anti-perlecan antibodies. A total of 108 patients diagnosed with anti-GBM disease between January 2000 and December 2018 were included in the study. Additionally, 100 patients with various active glomerular diseases were utilized as disease controls, along with 40 healthy controls. Immunoglobulin G (IgG) antibodies against perlecan were detected by enzyme-linked immunosorbent assay and immunoblot. Circulating IgG antibodies against perlecan were detected in 18.5% (20/108) of the anti-GBM patients but not in the healthy controls or other glomerular disease controls. Anti-perlecan IgG antibodies were predominantly of the IgG3 subclass. Patients with anti-perlecan autoantibodies had a higher prevalence of lung haemorrhage than those without (55.0% versus 26.1%; P=.012). A 'triple-positive' subgroup with anti-GBM disease was identified, who had circulating autoantibodies simultaneously against type IV collagen, laminin 521 and perlecan. This subgroup had the highest prevalence of lung haemorrhage [66.7% (10/15)] and incidence of end-stage kidney disease events [93.3% (14/15)], indicating a more aggressive immune-mediated tissue injury among these patients. Perlecan expands the repertoire of target antigens in anti-GBM disease. The discovery of autoantibodies against perlecan identified a 'triple-positive' subgroup with a more severe clinical phenotype among patients with anti-GBM disease. The pathogenic role of autoimmunity against perlecan and the pathophysiology of the co-existence of three autoantibodies merit further investigation in the future.

Goodpasture syndrome

The Alloantigenic Sites of α3α4α5(IV) Collagen: PATHOGENIC X-LINKED ALPORT ALLOANTIBODIES TARGET TWO ACCESSIBLE CONFORMATIONAL EPITOPES IN THE α5NC1 DOMAIN

BackgroundAnti-GBM disease is characterised by rapidly progressive glomerular nephritis with or without pulmonary haemorrhage. It is usually monophasic in nature and disease severity correlates with antibody titer. The disease is...

Anti–glomerular basement membrane disease during the COVID-19 pandemic

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it...