Goodpasture's Syndrome Research Articles

Rituximab for the Treatment of Anti-glomerular Basement Membrane Disease with Isolated Diffuse Alveolar Hemorrhage: A Case Report.

Anti-glomerular basement membrane (GBM) disease with isolated diffuse alveolar hemorrhage (DAH) is rare. We herein report a 91-year-old man admitted with hypoxia and diagnosed with anti-GBM disease with DAH based on positive bronchoalveolar lavage and serum antibody test results. There was no renal involvement. Although remission was achieved using glucocorticoids and plasmapheresis, the patient experienced DAH relapse one week after the last plasmapheresis. Rituximab 375 mg/m2 was administered 4 times weekly; thereafter, DAH relapse was not observed, and the glucocorticoid dosage was tapered. Rituximab was thus effective in treating anti-GBM disease with isolated DAH in an extremely elderly patient.

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment.

Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpasture's disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) (ClinicalTrials.gov identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients. In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data. Patients with a rebound (n=10) tended to have lower eGFR at 6months (11 vs 34mL/min/1.73 m2, P=.055), and patients with dialysis at 6months had a higher EB/EA ratio at rebound (0.8vs 0.5, P=.047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months. In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide.

Therapeutic plasma exchange for anti-glomerular basement membrane disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is treated with immunosuppressive medications and plasma exchange. However, whether plasma exchange, in addition to pulse glucocorticoid therapy, would benefit patients with anti-GBM disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage remains unclear.MethodsUsing the Japanese Diagnosis Procedure Combination database, we identified patients diagnosed with anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage from July 2010 to March 2020. We compared in-hospital mortality within 10 days of hospitalization between patients who received therapeutic plasma exchange in addition to pulse glucocorticoid therapy and those who received pulse glucocorticoid therapy alone. Overlap weighting based on propensity score was performed to adjust for potential confounders.ResultsWe identified 207 eligible patients; 168 patients received therapeutic plasma exchange plus pulse glucocorticoid therapy, while 39 patients received pulse glucocorticoid therapy alone. The mean dose of therapeutic plasma exchange was 52.2 ml/kg/day of albumin and/or fresh frozen plasma. Therapeutic plasma exchange in addition to pulse glucocorticoid therapy was associated with a lower in-hospital mortality risk in the unweighted (10.7% versus 28.2%; risk difference, 17.5%; 95% confidence interval, 2.6–32.4%; P = 0.02) and weighted analyses (11.5% versus 28.4%; risk difference, 17.0%; 95% confidence interval, 1.5–32.5%; P = 0.03) than pulse glucocorticoid therapy alone.ConclusionsThis retrospective cohort study using a national database suggests that therapeutic plasma exchange may improve the in-hospital prognosis of anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage.Graphical abstract

Primary membranous nephropathy in two siblings with one combined with anti-glomerular basement membrane disease: a case report

BackgroundThe phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear.Case presentationWe describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01.ConclusionWe describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

An unusual blend; IgA nephropathy and anti GBM disease

Anti-glomerular basement membrane (anti-GBM) disease is a rare illness with a wide spectrum of clinical manifestations. The typical presentation (90% of cases) of anti-GBM is with a rapidly progressive glomerulonephritis (RPGN) in conjunction with pulmonary disease in 25-60% of cases. In its atypical form – seen in 10% of cases, anti GBM disease takes on a chronic form, presenting with long standing renal dysfunction, proteinuria and better renal prognosis when compared to the typical form of the disease. The known associations of anti-GBM disease are with anti-neutrophil cytoplasmic antibody (ANCA)vasculitis and membranous nephropathy. In this case report, a young lady with atypical anti-GBM disease is described with a most unusual association with IgA nephropathy. This association is rare and only described in few case reports worldwide. The possible pathogenesis, clinical features, treatment and outcome of this disease are also elucidated.

#6879 ASSOCIATION OF THE BERDEN CLASSIFICATION AND THE PROGNOSIS OF ANCA VASCULITIS

Abstract Background and Aims ANCA-associated vasculitides (AAVs) are systemic diseases characterized by inflammatory involvement of the small vessel wall, and renal involvement is frequent and severe. The new Berden histo-pathological classification established in 2010 has made it possible to classify ANCA-associated glomerulonephritis (GAA) into focal, mixed, cellular, and sclerotic forms in order to better guide the therapeutic management and to assess the prognosis. The aim of this work was to evaluate the prognostic value of this anatomopathological classification. Method We conducted a single-center retrospective descriptive and analytical study of patients diagnosed with histologically confirmed GAA in our Nephrology Department during the period from 2016 to 2022. Results We collected 20 patients, median age 52 years [21-77 years]. The sex ratio (M/F) was 0.8. Histological confirmation of GAA was based on renal biopsies in 100% of cases. Rapidly progressive glomerulonephritis was the nephrological presentation in 15 patients. One patient had no hematuria and one had no proteinuria and renal failure was present in all cases. Good Pasture syndrome was present in 7 cases. The Berden classification was applied to the 20 renal biopsies: the focal form (2 cases), the cellular form (7 cases), the mixed form (7 cases) and the sclerotic form (4 cases). The evolution was marked by a partial remission for 11 patients. After an evolution of 1 year, end-stage renal failure (ESRD) was retained in 13 patients. The sclerotic form was not associated with a poor prognosis in our population (p = 0.642). Conclusion Of course, our sample size was small and in our population we found a predominance of the mixed and cellular forms compared to the sclerotic form, contrasting with poor therapy with a rapid evolution towards CKD.

#5132 POST-COVID-19 ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE: TWO CLINICAL CASES

Abstract Background and Aims Acute kidney injury is a common complication in patients hospitalized with COVID-19, has multiple aetiologies, and is usually multifactorial. We present two cases of anti-glomerular basement membrane (anti-GBM) disease diagnosed after SARS-CoV-2 infection, suggesting a causal correlation. Case Reports A 76-year-old female, with chronic kidney disease (serum creatinine 1.5mg/dL), hypertension, weight loss (16 Kg/6 months) and a pancreatic nodule under surveillance, presented to the emergency department with 1 week of nausea, vomits, diarrhoea and oliguria, as well as a history of mild SARS-CoV-2 infection 2 weeks before presentation. Lab work revealed severe anaemia (7.4 g/dL), inflammatory markers elevation, nephrotic proteinuria (proteinuria/creatininuria ratio 30 g/g), leucoerythrocyturia, serum creatinine of 19.3 mg/dL, hyperkalaemia and metabolic acidosis requiring dialysis induction. Renal ultrasound showed signs of chronicity and several cysts. Aetiological study disclosed positive anti-GBM antibody (1800 U/L) and negative ANCA. Complementary study failed to identify pulmonary involvement or neoplasms. Given the severity of the renal dysfunction along with the absence of alveolar haemorrhage, immunosuppression and plasmapheresis were not initiated. Patient was discharged and remains dialysis dependent. A 65-year-old male smoker with type 2 diabetes and combined pulmonary fibrosis and emphysema, presented in the emergency department with 2 months of asthenia, weight loss and anaemia, in addition to dyspnoea and haemoptysis in the past 3 days. Lab work exposed moderate anaemia (9.7 g/dL), elevated inflammatory markers, serum creatinine of 1.18 mg/dL (previously 0.8 mg/dL), leucoerythrocyturia and positive SARS-CoV-2 test. Angio-Computed Tomography exhibited known pulmonary fibrosis and possible bacterial superinfection. Despite antibiotic therapy (10 days of levofloxacin), haemoptysis remained and kidney function continuously worsened (serum creatinine 2.1 mg/dL). Complementary study showed positive ANCA-MPO (1125.4 U/L) and anti-GBM antibody (460.8U/L). Renal ultrasound was innocent. Kidney biopsy revealed: 6 glomeruli with cellular crescents with segmental necrosis, 3 with focal Bowman's capsule rupture; erythrocyte casts; intimal arterial fibrosis; moderate tubular atrophy; diffuse linear deposits of IgG. Immunosuppression was initiated with prednisolone (1 mg/Kg/day), cyclophosphamide (3x 12.5mg/Kg-750 mg, 2x 500 mg), rituximab (2x 1g), immunoglobulin (1x 2 g/Kg) and plasmapheresis (15 sessions). Kidney function continued to deteriorate (maximum serum urea 306 mg/dL, maximum serum creatinine 6.92 mg/dL) requiring dialysis induction 3 weeks after the beginning of immunosuppression. Even though haemoptysis ceased, the patient remains dialysis dependent 8 months after. Conclusion Literature reports an increase of Anti-GBM disease since the beginning of the pandemic. The presented cases support the apparent correlation, suggesting SARS-CoV-2 as a precipitant of this disease by endothelial injury with basal membrane exposure and autoantibody development. In the second case, the authors assume a subacute ANCA-MPO vasculitis with superimposed anti-GBM (eventually precipitated by COVID-19). Even though the causal association is not established, we highlight the importance of clinical suspicion of this rare aetiology in cases of acute kidney injury after SARS-CoV-2 infection.

Pulmonary Pneumocystis in HIV-Negative Patients: About 13 Cases

We present thirteen examples of pulmonary pneumocystis (PCP) in patients without HIV infection. Eight men and five women, average age 55, with one instance of breast neoplasia, two cases of DICV, one case of "Goodpasture's syndrome," one case of idiopathic fibrosing PINS treated with extended corticotherapy for two years, and the other patient without known immunosuppression. In 11 cases, there is persistent dyspnea and severe hypoxia. Lymphopenia (9 instances), with a 920.76 element/mm3 average rate. Except in two cases where examination of the bronchoalveolar lavage fluid was required, the diagnosis was established by the isolation of Pneumocystis jiroveci in the induced sputum. The evolution was positive in every case while receiving trimethoprine-sulfametaxazole and corticosteroid therapy.

Goodpasture’s Syndrome in Children: About a Case Report

Pulmonary-renal syndrome is a medical condition that encompasses a range of clinical symptoms that can appear in various diseases. It is identified by the occurrence of both pulmonary hemorrhage and glomerulonephritis. While this syndrome is rare in children, it can pose a medical emergency if it does occur. Goodpasture's syndrome (GPS) is one of the infrequent causes of pulmonary-renal syndrome in childhood. This article presents a case study detailing the diagnosis of Goodpasture's Syndrome in a 5-year-old pediatric patient with a medical history of nephrotic syndrome, glomerulonephritis at end-stage renal failure, and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The patient was admitted to the emergency department due to hemoptysis, a hallmark symptom of this syndrome.

Good-Pasture Syndrome: A Rare Entity, about two Observations

Goodpasture syndrome is an uncommon autoimmune disorder that can harm the lungs and kidneys. This condition occurs when the body's immune system mistakenly targets and damages the tissues in these organs. The antibodies produced by the body attack the collagen in the basement membrane of the lungs and kidneys, which results in inflammation and injury to these organs. Symptoms of Goodpasture syndrome include tiredness, coughing up blood, breathing difficulties, and kidney failure. Diagnosis typically involves blood and urine tests to look for the specific antibodies associated with the syndrome, as well as imaging tests to assess the extent of lung and kidney damage. We report two cases of Good-Pasture syndrome admitted to the emergency room with alveolar hemorrhage, whose anatomopathological examinations later confirmed the diagnosis.

146 Development of a Mathematical Model for Cost Calculation and Sustainability Analysis of Beef Cattle Grazing Systems

Abstract A mathematical model to estimate: a) the cost of beef cattle production in grazing systems; and b) the environmental sustainability of production systems using the Emergy Synthesis Model was evaluated. All items were considered and allocated, according to the precepts of the Economic Theory, under Fixed Cost (FC), Variable Cost (VC), and Total Cost (TC). The model estimated costs in the case-study for the entire property and the different production lots within the same property. Costs were allocated per animal and per kg of beef cattle produced. The total cost per animal of cattle produced was US$ 416.86. It was observed that the VC represented 66% of the TC. The cattle purchase price, including under VC, was the factor that represented the most significant portion of the production cost, in which the current operation reached 59% of the TC. Therefore, the currently developed tool may be used to facilitate understanding and potentially help to manage risk and profit. To examine from the environmental point of view, the synthesis of emergy was utilized. Emergy is the memory of the available energy used directly and indirectly to produce a service or product. It was observed that the property considered in the current case-study showed a renewability of 47.6%, indicating that less than one-half of all the energy used came from renewable resources. The emergetic yield ratio (EYR), which measures how much natural energy was incorporated into produced goods or services, was 1.91. The survey showed that the emergetic exchange ratio (EER), which indicates how balanced the exchange ratio between the energy in products and the energy gross revenue, was 12.45, showing that the system delivers much more energy than it receives in a monetary form. It seems like the current system analysis was highly dependent on cost-effective resources. The fuel used for pasture management services was the non-renewable resource that mostly affected the design. For the emergy synthesis, such input represented 51.2% of the total energy used, but from the economic point of view, such resource represented only 1% of the total production cost. The system could be less dependent on market variability if good pasture management practices were adopted, such as using a reasonable pasture stocking rate. By using the emergy indexes, it was possible to analyze the cattle system from an environmental perspective, allowing to assist technology/technique adoptions capable of increasing the sustainability indicators, which has been recently valued by worldwide beef consumers.

Oral ulceration as a revealing sign of granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), formerly called Wegener's granulomatosis, is a rare systemic disease of unknown etiology that can affect all areas of the body, including the oral cavity. Typical oral manifestations present as nonspecific erosive/ulcerative lesions of the oral mucosa or appear with hyperplastic gingivitis, termed “strawberry gingivitis”. We report here a case of cheek ulceration as the first sign of recurrence of GPA in the absence of oral manifestations in the primary disease. A 37-year-old woman was referred to our oral pathology and surgery department for oral ulcerations. The patient had already been diagnosed with GOODPASTURE syndrome (pneumorenal syndrome) two years previously and treated with cyclophosphamide and Azathioprine. Its relapse and the appearance of oral manifestations made it possible to readjust the diagnosis and the treatment.

Anti-glomerular Basement Membrane Disease Concomitant with MPO-ANCA Positivity Concurrent with High Serum Levels of Interleukin-26 Following Coronavirus Disease 2019 Vaccination.

As coronavirus disease 2019 (COVID-19) vaccine booster campaigns progress worldwide, new reports of complications following COVID-19 vaccination have emerged. We herein report a case of new-onset anti-glomerular basement membrane (GBM) disease concomitant with myeloperoxidase-antineutrophil cytoplasmic antibody positivity concurrent with high levels of interleukin (IL)-26 following the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal association with vaccination in this case suggests that an enhanced neutrophilic immune response through IL-26 may have triggered necrotizing glomerulonephritis and a T-cell-mediated immune response to GBMs, leading to the development of anti-GBM antibodies, with an enhanced B-cell response after the vaccination triggering anti-GBM IgG and the onset of anti-GBM disease.

317 Case of Goodpasture syndrome With Double-Positive Anti-Glomerular Basement Membrane (GBM) and Myeloperoxidase-Anti Neutrophil Cytoplasmic Antibodies (MPO-ANCA)

317 Case of Goodpasture syndrome With Double-Positive Anti-Glomerular Basement Membrane (GBM) and Myeloperoxidase-Anti Neutrophil Cytoplasmic Antibodies (MPO-ANCA)

Clinical and immunological characteristics of patients with combined anti-glomerular basement membrane disease and IgA nephropathy.

The combination of anti-glomerular basement membrane (GBM) disease and immunoglobulin A nephropathy (IgAN) has been well documented in sporadic cases, but lacks overall assessment in large collections. Herein, we investigated the clinical and immunological characteristics and outcome of this entity. Seventy-five consecutive patients with biopsy-proven anti-GBM disease from March 2012 to March 2020 were screened. Among them, patients with concurrent IgAN were identified and enrolled. The control group included biopsied classical anti-GBM patients during the same period, excluding patients with IgAN, other glomerular diseases or tumors, or patients with unavailable blood samples and missing data. Serum IgG and IgA autoantibodies against GBM were detected by enzyme-linked immunosorbent assay, as were circulating IgG subclasses against GBM. Fifteen patients with combined anti-GBM disease and IgAN were identified, accounting for 20% (15/75) of all patients. Among them, nine were male and six were female, with an average (± standard deviation) age of 46.7±17.3 years. Thirty patients with classical anti-GBM disease were enrolled as controls, with 10 males and 20 females at an average age of 45.4±15.3 years. Patients with combined anti-GBM disease and IgAN had restricted kidney involvement without pulmonary hemorrhage. Compared with classical patients, anti-GBM patients with IgAN presented with significantly lower levels of serum creatinine on diagnosis (6.2±2.9 vs 9.5±5.4mg/dL, P=.03) and less occurrence of oliguria/anuria (20%, 3/15 vs 57%, 17/30, P=.02), but more urine protein excretion [2.37 (1.48, 5.63) vs 1.11 (0.63, 3.90) g/24h, P=.01]. They showed better kidney outcome during follow-up (ESKD: 47%, 7/15 vs 80%, 24/30, P=.03). The autoantigen and epitope spectrum were comparable between the two groups, but the prevalence of circulating anti-α3(IV)NC1 IgG1 (67% vs 97%, P=.01) and IgG3 (67% vs 97%, P=.01) were lower in patients with IgAN. Concurrent IgAN was not rare in anti-GBM disease. Patients showed milder kidney lesions and better recovery after immunosuppressive therapies. This might be partly explained by lower prevalence of anti-GBM IgG1 and IgG3 in these patients.

Case Report: Bilateral Lung Transplantation for Rapidly Progressive Undifferentiated Interstitial Lung Disease—A Cautionary Tale

Interstitial lung disease is fast becoming one of the most common indications for lung transplantation (LTx); however, LTx for Goodpasture's syndrome with pulmonary involvement has not been previously described in the literature. In this report, we outline the case of a young male with undifferentiated rapidly progressive interstitial lung disease who ultimately received a bilateral sequential LTx after deterioration requiring extracorporeal membrane oxygenation. The original disease soon recurred in the graft, and unfortunately, the patient did not survive. The diagnosis of Goodpasture's syndrome was made postmortem and was not clearly evident on examination of the native explanted tissue, nor was there an elevated titer of antiglomerular basement membrane antibodies during his initial work-up. We hypothesize that the donor and recipient's HLA profile made him more susceptible to aggressive disease. In hindsight, active Goodpasture's disease would have been a contraindication to proceed to transplantation. This case is a cautionary reminder of the high stakes of performing LTx without a certain diagnosis.

28 An Interesting Case of Anti-Glomerular Basement Membrane Disease Mediated by IgA Autoantibodies

28 An Interesting Case of Anti-Glomerular Basement Membrane Disease Mediated by IgA Autoantibodies

"Double Positive Anti-GBM and ANCA Along with Hyponatremia: Case Report"

On rare occasions, patients with Goodpasture’s syndrome (GPS) present with both anti-glomerular basement membrane (GBM) and antineutrophil cytoplasmic antibody (ANCA). Concurrent ANCA and anti-GBM disease is rare with a high mortality rate. Here we present a case of both anti-glomerular basement membrane (GBM) and antineutrophil cytoplasmic antibody (ANCA) complicated with hyponatremia.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

Effects of climate change on community based grazing lands management: A case study of the border between Nigeria and Niger Republic

In recent years, climate changes have had serious and unprecedented effects in Nigeria and Niger Republic. These changes range from a rapid decrease in forest resources to social and economic effects with obvious environmental repercussions. This paper examined the effect of climate change on community based grazing land management between the border of Nigeria and the Niger Republic. The focus was made on identifying activities carried out in the area, identifying herders’ encroachment routes and the perceived occurrence of climate change. Thus, data from Focus Group Discussions (FGD) and Questionnaire derived from the inhabitants were collected and analyzed. A total of 1,009 questionnaires out of the 1,020 given were used to collect data for the study. The results revealed that various forms of changing climatic patterns force arable farming into more and more marginal areas. When there is heavy pressure on grazing lands, the animals consume palatable vegetation faster than it can generate, and eventually, no vegetation remains. Continuing overgrazing is detrimental in the study area because it reduces primary productivity, impedes plant growth and survival and consequently alters species composition of the grasses, shrubs and forbs that provide livestock with food. The study further revealed that moderate grazing pressure increased plant diversity and soil and land health. Therefore, good pasture management is a remedy to sustainable utilization, among which proper grazing management serves as the key element of sustainable rangeland restoration. The study further recommends that the conservation of grazing land is the responsibility of all.