anti-GBM Antibody Disease Research Articles

Anti-Glomerular Basement Membrane Antibody Disease: Clinicopathologic Profile and Outcomes

Background: Anti-glomerular basement membrane antibody disease is a rare autoimmune disease caused by antibodies to α3 chain of type 4 collagen. Patients presenting with severe renal involvement requiring dialysis have poor response to treatment. Materials and Methods: We conducted a retrospective and prospective study at Institute of Nephrology, Madras Medical College, Chennai, India by analyzing the data of patients with biopsy-proven anti-GBM antibody disease treated from January 2013 to December 2019. Results: There were 2,949 kidney biopsies in the study period and 92 showed crescentic glomerulonephritis (GN). Of those, 20 patients (10 males) had anti-GBM antibody disease. Mean age was 40.75 ± 14.75 years. Rapidly progressive renal failure was the most common mode of presentation (95%); five (25%) patients had diffuse alveolar hemorrhage (DAH) and nineteen patients (95%) required dialysis at presentation. Seven patients (35%) were positive for anti-neutrophil cytoplasmic antibody (anti-myeloperoxidase in six and anti-proteinase 3 in one). Of the twelve patients (60%) who received immunosuppression (cyclophosphamide, steroids, and plasma exchange), two patients (10%) attained remission, and two patients (10%) expired due to sepsis. Crescentic GN was the predominant pathology in kidney biopsy in 19 patients (95%). Mesangial hypercellularity with deposition of IgA and C3 in mesangium was present in one patient. Conclusion: In our study, anti-GBM antibody disease accounted for 21.7% of crescentic GN. Majority of patients presented late, requiring dialysis. Patient survival was 90%, while renal survival was only 10%. One patient had co-occurrence of IgA nephropathy with anti-GBM antibody disease.

Subsequent COVID-19 Prophylaxis in COVID-19 Associated Glomerulopathies.

Successful vaccination has been the decisive factor in the overall decline of SARS-CoV2 infection related morbidity and mortality. However, global effects of the COVID-19 pandemic are ongoing, with reports of glomerular disease occurring in relation to both infection and vaccination. A particular rise in anti-GBM disease has been identified. Information is still emerging regarding the optimal management of such cases. We reviewed anti-GBM antibody detection rates at our test center over the past 5 years. We followed three patients with biopsy confirmed glomerular disease temporally related to COVID-19 vaccination. Each patient proceeded to receive subsequent COVID-19 vaccination as per immunologist recommendations. Further assessment included COVID-19 antibody testing in each case. A three-fold increase in significant anti-GBM antibody results noted at our center was associated with COVID infection in 10% of cases, and COVID vaccination in 25% of cases. We demonstrated that subsequent vaccination did not appear to lead to adverse effects including relapse in our three cases of COVID-19 vaccine-associated GN. We also identified positive COVID-19 antibody levels in two out of three cases, despite immunosuppression. We report a rise in anti-GBM antibody disease incidence. Our small study suggests that COVID-19 antibody testing can help determine COVID prophylaxis requirements, and subsequent vaccination with an alternative vaccine type appears safe.

СИНДРОМ ГУДПАСЧЕРА С УМЕРЕННЫМ ПОРАЖЕНИЕМ ПОЧЕК И ТОРПИДНЫМ ТЕЧЕНИЕМ ЛЁГОЧНОГО ПРОЦЕССА: КЛИНИЧЕСКИЙ СЛУЧАЙ

Anti-GBM antibody disease (Goodpasture syndromee) is a rare immunecomlpex vasculitis, affecting small vessels, and characterized by rapidly progressive glomerulonephritis and alveolitis. Causative mechanism is defined by the hyperproduction of autoantibodies against the α3-chain of type IV collagen (Goodpasture antigen) with immune complex formation on the glomerular and alveolar basement membrane. Typically patients with fnti-GBM antibody disease present with rapidly progressive (crescentic) glomerulonephritis, more than in half of cases associated with alveolar hemorrhage. Cases of Anti-GBM antibody disease with atypical clinical presentation have been reported. We report a case of atypical clinical presentation anti-GBM antibody disease with mild renal damage and slow progression of pulmonary involvement. Main CT signs were multiple centrilobular ground glass nodules. This case report demonstrates that CT with disseminated pulmonary process associated with even mild kidney involvement in patients with high anti-GBM antibodies titers gives a clue to the diagnosis of anti-GBM antibody disease.

Acquired aplastic anemia complicated with anti-glomerular basement membrane disease successfully treated with immunosuppressive therapy: a case report

BackgroundAplastic anemia (AA) is a rare but fatal disorder characterized by pancytopenia due to bone marrow hypoplasia. Anti-glomerular basement membrane disease (anti-GBM disease) is an immune complex small-vessel vasculitis that presents as rapidly progressive glomerulonephritis and/or pulmonary hemorrhage. Although both involve autoreactive T cells that are partially triggered by human leukocyte antigen (HLA)-DR15, there have been no reports of their co-existence and the treatment strategy is not well understood.Case presentationA 67-year-old woman presented with fever, malaise, and acute kidney injury with proteinuria and hematuria requiring hemodialysis. She was diagnosed with anti-GBM antibody disease based on high serum anti-GBM antibody titer and crescentic glomerulonephritis on a renal biopsy. Pulse administration of methylprednisolone (MP), oral prednisolone (PSL), and plasmapheresis were performed. Only 2 weeks after the diagnosis of anti-GBM disease, the patient developed pancytopenia requiring frequent blood transfusions. The blood cell count did not recover even 1 month after discontinuing the drugs that could cause pancytopenia. Bone marrow examination showed hypocellularity without abnormal infiltrates or fibrosis, which led to the diagnosis of severe acquired AA. Further HLA phenotyping revealed that she had HLA-DR15. Increased dose of PSL with the secondary MP pulse and the addition of cyclosporine improved pancytopenia. Although she remained dialysis-dependent, anti-GBM disease and pancytopenia did not recur for more than 2 years.ConclusionsWe report the first case of acquired AA complicated with anti-GBM disease in an elderly woman with HLA-DR15, which was successfully treated with immunosuppressive therapy (IST). This report is valuable not only because it shows they may co-occur, but also because it provides a therapeutic option for this complex condition. It was also suggested that pancytopenia in patients with anti-GBM disease recalls serious hematologic diseases including AA that require immediate treatment based on bone marrow examination.

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

Rapid progressive anti-GBM glomerulonephritis with multiple auto-antibodies

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by progressive loss of renal function in a short period. At renal biopsy, it is characterized by crescent formation. RPGN may be associated with the presence of circulating antibodies. We report a case of type IV RPGN [ANCA and Anti–glomerular basement membrane (anti-GBM) antibody disease], a severe disease causing a difficult to treat picture. Our case was complicated by severe thrombocytopenia due to the use of heparin and later on by thrombotic microangiopathy. These events occurred rapidly, making the clinical framing and management decisions very hard.

Characteristics and Outcomes of Patients with Anti-Glomerular Basement Membrane Antibody Disease and Anti-Neutrophil Cytoplasmic Antibodies.

It is unclear whether patients with Anti-Glomerular Basement Membrane (GBM) disease and Anti-Neutrophil Cytoplasmic Antibodies (ANCA), so called "Double-Positive" (DP), have a different clinical presentation and outcome compared to patients with anti-GBM antibody disease alone. This study describes the clinical and histologic characteristics as well as the patient and renal outcomes of DP patients at the University of Washington compared to patients with anti-GBM antibody disease alone. Adults admitted to the University of Washington and Harborview Medical Centers from 2000 to 2016 who had a kidney biopsy showing anti-GBM disease characterized by crescentic glomerulonephritis with strong linear staining of glomerular basement membranes for IgG by immunofluorescence were included. Subjects were classified into anti-GBM or DP based on serologic testing. Information on demographics, clinical presentation, biopsy findings, initial treatment, and rates of relapse and patient and renal survival were collected. Continuous and categorical variables were analyzed using the Mann-Whitney U and Fisher's exact tests, respectively. There were 6 anti-GBM and 7 DP patients. Two patients were lost to follow-up after one year. There was no significant difference in clinical presentation or outcomes between the two groups. Two DP patients had greater than 50% global glomerulosclerosis. All the subjects developed ESRD. Two DP patients had a relapse while off immunosuppression. Two patients in each group died within 5 years of diagnosis. Two DP patients in our cohort had a relapse within 5 years of diagnosis. Multicenter studies are needed to determine whether DP patients have a higher relapse rate and need prolonged immunosuppression.

The Diagnostic and Clinical Utility of Autoantibodies in Systemic Vasculitis

Considerable progress has been made in understanding the role of autoantibodies in systemic vasculitides (SV), and consequently testing for anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane antibodies (anti-GBM), and anti-C1q antibodies is helpful and necessary in the diagnosis, prognosis, and monitoring of small-vessel vasculitis. ANCA-directed proteinase 3 (PR3-) or myeloperoxidase (MPO-) are sensitive and specific serologic markers for ANCA-associated vasculitides (AAV), anti-GBM antibodies are highly specific for the patients with anti-GBM antibody disease (formerly Goodpasture’s syndrome), and autoantibodies to C1q are characteristic of hypocomlementemic urticarial vasculitis syndrome (HUVS; anti-C1q vasculitis). The results of a current EUVAS study have led to changes in the established strategy for the ANCA testing in small-vessel vasculitis. The revised 2017 international consensus recommendations for ANCA detection support the primary use PR3- and MPO-ANCA immunoassays without the categorical need for additional indirect immunofluorescence (IIF). Interestingly, the presence of PR3- and MPO-ANCA have led to the differentiation of distinct disease phenotype of AAV: PR3-ANCA-associated vasculitis (PR3-AAV), MPO-ANCA-associated vasculitis (MPO-AAV), and ANCA-negative vasculitis. Further studies on the role of these autoantibodies are required to better categorize and manage appropriately the patients with small-vessel vasculitis and to develop more targeted therapy.

160 Unusual Case of Anti-GBM Antibody Disease: Presenting with Microangiopathic Hemolytic Anemia

160 Unusual Case of Anti-GBM Antibody Disease: Presenting with Microangiopathic Hemolytic Anemia

Difficulties in Goodpasture's syndrome diagnosing.

The article analyzes the diagnosis and treatment of anti-GBM antibody disease (Goodpasture's syndrome) - a rare, severe progressive disease, associated with anti-glomerular basement membrane antibody-induced pulmonary hemorrhage and glomerulonephritis. The main problem of this pathology is late diagnosis, resulted in ineffective treatment. The article provides current information on the epidemiology, etiology and pathogenesis, diagnosis, and treatment of Goodpasture's syndrome, as well as clinical case of a patient with this rare disease.

Good Pasture Syndrome-A Case Presentation

Good pasture syndrome (GPS), also known as Pneumorenal Syndrome or anti-glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure. Currently, the preferred term for both conditions is “anti-GBM antibody disease”. Circulating antibodies are directed against the collagen of the part of the kidney known as the glomerular basement membrane (GBM), leading to bleeding from the lungs and kidney failure. Antibodies also attack the collagen of the air sacs of the lung (alveoli) resulting in bleeding of the lung (pulmonary hemorrhage). Good pasture syndrome is fatal unless quickly diagnosed and treated. (Magalini SI, et al, 1997)

Investigations in systemic vasculitis. The role of the laboratory.

The diagnosis of systemic vasculitis is challenging. Laboratory testing may provide useful information. Routine laboratory tests include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulin, cryoglobulin, and Hepatitis B and C serology. Although ESR and CRP are often helpful for the diagnosis of vasculitis, they are nonspecific and do not help in distinguishing between vasculitis disease activity and a concomitant infection or another source of inflammation. A few autoantibodies are helpful for diagnosis, such as anti-neutrophil cytoplasmic antibodies (ANCAs) (in ANCA-associated small-vessel vasculitis), anti-glomerular basement membrane (GBM) antibodies (in anti-GBM antibody disease), and anti-C1q antibodies (in immune complex-associated small-vessel vasculitis). The 2017 revised consensus recommendations on ANCA testing state that high-quality antigen-specific immunoassays are the preferred screening methodology for the diagnosis of ANCA-associated vasculitis. ANCA subtypes (proteinase-3-ANCA and myeloperoxidase-ANCA) are associated with different epidemiological, genetic, and clinical features.

Goodpasture's Syndrome with Negative Anti-glomerular Basement Membrane Antibodies.

A young male patient with rapidly progressive and life-threatening pulmonary haemorrhage due to anti-glomerular basement membrane (anti-GBM) antibody disease without renal involvement repeatedly tested negative for serum anti-GBM antibodies. Although rare, anti-GBM antibody disease should be considered in the differential diagnosis in patients with life-threatening pulmonary haemorrhage due to isolated diffuse alveolar haemorrhage. Enzyme-linked-immunosorbent assay (ELISA) testing for anti-GBM antibodies in anti-GBM antibody disease can give false-negative results. A negative serum anti-GBM antibody test is therefore insufficient to exclude the diagnosis. Thus, a kidney or lung biopsy should be considered in any case with a high clinical suspicion but negative anti-GBM antibody test to confirm or rule out the diagnosis.LEARNING POINTSDiffuse alveolar haemorrhage (DAH) is a life-threatening disorder caused by severe damage due to injury or inflammation of the alveolar-capillary basement membrane.Anti-GBM antibody disease is a rare autoimmune disorder with circulating autoantibodies directed against the alpha-3 chain[Q2] of type VI collagen of the glomerular and/or alveolar basement membrane which may result in oliguric acute kidney failure due to rapidly progressive glomerulonephritis with or without DAH (commonly referred to as Goodpasture’s syndrome).A kidney or lung biopsy should be considered to confirm or rule out the diagnosis if there is a high clinical suspicion but the anti-GBM antibody test is negative; prompt diagnosis and initiation of plasmapheresis, cyclophosphamide and prednisone therapy is essential.

A "Mini-Epidemic" of anti-glomerular basement membrane disease: Clinical and epidemiological study.

Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM) antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17-80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5-7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted?

Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occurrence, symptoms resolved with plasmapheresis, intravenous methylprednisone and oral cyclophosphamide. The relationship between anti-GBM antibody findings and disease presentation is complex. Clinicians should be aware of the possibility of seronegative anti-GBM disease.

65-Year-Old Woman With Intermittent Fevers, Lower Extremity Paresthesia, Weight Loss, and Malaise

65-Year-Old Woman With Intermittent Fevers, Lower Extremity Paresthesia, Weight Loss, and Malaise

A Case of Anti-Glomerular Basement Membrane Antibody Disease in Siblings

Anti-glomerular basement membrane (anti-GBM) antibody disease, also known as Goodpasture syndrome, is associated with the presence of antibodies against type 4 collagen. Increasing evidence supports the role of human leukocyte antigen (HLA) genes in the pathogenesis of this disease. A 48-year-old Caucasian male was admitted to the intensive care unit with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. Serology demonstrated high anti-GBM antibodies (291.8 U/L). Renal biopsy showed crescentic glomerulonephritis involving 16 of 19 glomeruli with strong linear and diffuse IgG staining confirming the diagnosis of anti-GBM antibody disease. The patient’s sister presented with pulmonary-renal syndrome at age 29 due to the same illness. Subsequent HLA typing revealed that our patient was homozygous for DRB1*15:01, an allele strongly associated with anti-GBM antibody disease. To our knowledge, this is the first case report of anti-GBM antibody disease in a patient who is homozygous for DRB1*15:01 with a sibling who had the same diagnosis. Our case highlights the importance of HLA genes in the pathogenesis of this disease. World J Nephrol Urol. 2015;4(1):178-180 doi: http://dx.doi.org/10.14740/wjnu198w

Propylthiouracil-associated rapidly progressive crescentic glomerulonephritis with double positive anti-glomerular basement membrane and antineutrophil cytoplasmic antibody: the first case report.

We report a case of propylthiouracil (PTU)-induced double antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai woman with 10-year history of PTU treatment for thyrotoxicosis. She developed clinical symptoms of vasculitis upon receiving long-term PTU treatment. Prednisolone treatment and the switching from PTU to methimazole resulted to short-term clinical improvement. Nevertheless following termination of steroid treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with linear IgG deposit on the glomerular basement membrane although transbronchial lung biopsy showed no immune deposit along the alveolar basement membrane. Serum testing for p-ANCA was positive and western blot showed positive antibody to the alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a role in the development of end organ damage. To facilitate early and specific intervention, clinicians should be aware of the propensity of PTU to cause lupus-like syndromes with renal involvement. In patients with PTU-induced ANCA-associated glomerulonephritis, serum anti-GBM antibody test may be useful in the early diagnosis of double positive antibodies disease and plasmapheresis should be performed without delay.

A Fulminant Case of Anti-GBM Antibody Disease Without Renal Symptoms

A Fulminant Case of Anti-GBM Antibody Disease Without Renal Symptoms

Update on crescentic glomerulonephritis.

The recent years have seen a number of major progresses in the field of extracapillary glomerulonephritis. This entity is the final damage caused by unrelated immunological disorders such as immune complexes glomerular deposits or microvascular injury caused by proinflammatory cytokines, neutrophil extracellular traps (NET), and cell adhesion molecules in the context of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This review provides a summary of recent advances in the understanding of crescentic glomerulonephritis, focusing on interplays of local immune cells and on local mediators participating to crescent formation especially in anti-glomerular basement membrane (anti-GBM) antibody disease. The recent advances about AAV and lupus nephritis are covered by other chapters of this issue. Nevertheless, these considerations may apply to the general case of crescentic glomerulonephritis of all causes.