Antiglomerular Basement Membrane Disease

2018 ◽  
Vol 39 (04) ◽  
pp. 494-503 ◽  
Author(s):  
Charles Pusey ◽  
Stephen McAdoo
Keyword(s):  
Basement Membrane ◽  
Rapidly Progressive Glomerulonephritis ◽  
Basement Membranes ◽  
Alveolar Hemorrhage ◽  
Type Iv ◽  
Maintenance Immunosuppression ◽  
Life Threatening ◽  
Renal Prognosis ◽  
Function Testing

AbstractAntiglomerular basement membrane (anti-GBM) disease is a rare but life-threatening autoimmune vasculitis that is characterized by the development of pathogenic autoantibodies to type IV collagen antigens expressed in the glomerular and alveolar basement membranes. Once deposited in tissue, these autoantibodies incite a local capillaritis which manifests as rapidly progressive glomerulonephritis (GN) in 80 to 90% of patients, and with concurrent alveolar hemorrhage in ∼50%. A small proportion of cases may present with pulmonary disease in isolation. Serological testing for anti-GBM antibodies may facilitate rapid diagnosis, though renal biopsy is often required to confirm the presence of necrotizing or crescentic GN and linear deposition of autoantibody on the glomerular basement membrane. Alveolar hemorrhage may be evident clinically, or detected on imaging, pulmonary function testing, or bronchoscopy. Prompt treatment with plasmapheresis, cyclophosphamide, and steroids is usually indicated to remove pathogenic autoantibodies, to prevent their ongoing production, and to ameliorate end-organ inflammation. Alveolar hemorrhage is usually responsive to this treatment, and long-term respiratory sequelae are uncommon. Renal prognosis is more variable, though with aggressive treatment, independent renal function is maintained at 1 year in more than 80% of patients not requiring renal replacement therapy at presentation. Relapse in uncommon in anti-GBM disease, unless there is a concomitant antineutrophil cytoplasm antibody (present in 30–40%), in which case maintenance immunosuppression is recommended.

Antiglomerular basement membrane disease

2020 ◽  
pp. 4943-4950
Author(s):  
Mårten Segelmark ◽  
Thomas Hellmark
Keyword(s):  
Basement Membrane ◽  
Age Distribution ◽  
Rapidly Progressive Glomerulonephritis ◽  
Strongly Correlated ◽  
Crescent Formation ◽  
Type Iv ◽  
Renal Prognosis ◽  
High Doses ◽  
Pathogenic Antibodies

Antiglomerular basement membrane (anti-GBM) disease, also known as Goodpasture’s disease, is a rare autoimmune kidney and/or lung disease caused by autoantibodies directed against the noncollagenous, C-terminal domain of the α‎3 chain of type IV collagen (α‎3(IV)NC1). Epidemiology—bimodal age distribution with peaks in the third and sixth/seventh decades; incidence 0.5 to 2/million population/year. Clinical features—typically presents as a renopulmonary syndrome with the combination of rapidly progressive glomerulonephritis and lung haemorrhage, but can present with isolated glomerulonephritis. Pathology—light microscopy typically reveals crescent formation, often in more than 80% of glomeruli, with linear staining of IgG along the GBM. Management—aside from supportive care, this typically consists of (1) stopping the inflammatory process with high doses of corticosteroid, (2) removal of the pathogenic antibodies by plasma exchange, and (3) stopping production of new antibodies with cyclophosphamide. It is controversial whether patients presenting with dialysis dependency and no pulmonary disease benefit from immunosuppression. Prognosis—recent series report mortality at 6 to 12 months of 7 to 36%, with patients’ survival mainly dependent on age and renal function at diagnosis. The most important factor in renal prognosis is the glomerular filtration rate at diagnosis, which is strongly correlated to the proportion of crescents seen in the renal biopsy. Very few patients with dialysis dependency at diagnosis regain enough function to become dialysis independent (0–7% most series). Patients do not need long-term immunosuppression, and the disease rarely recurs. Renal transplantation is safe if performed after autoantibodies have been suppressed or naturally disappeared.

scholarly journals SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alexander Winkler ◽  
Emanuel Zitt ◽  
Hannelore Sprenger-Mähr ◽  
Afschin Soleiman ◽  
Manfred Cejna ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Plasma Cells ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Pulmonary Involvement ◽  
Pulmonary Haemorrhage ◽  
Basement Membranes ◽  
High Avidity ◽  
History Of

Abstract Background Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. Case presentation The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. Conclusion Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

scholarly journals Atypical Goodpasture’s disease: a clinical case report and literature review

2018 ◽  
Vol 90 (6) ◽  
pp. 130-136 ◽  
Author(s):  
M L Bulanova ◽  
D V Potapov ◽  
N M Bulanov ◽  
L V Lysenko(Kozlovskaya)
Keyword(s):  
Basement Membrane ◽  
Renal Involvement ◽  
Rapidly Progressive Glomerulonephritis ◽  
Young Male ◽  
Alveolar Hemorrhage ◽  
Disease Course ◽  
Small Vessels ◽  
Goodpasture's Disease ◽  
Pulmonary Renal Syndrome ◽  
Goodpasture’S Disease

Goodpasture’s disease (anti-GBM disease) is a rare small vessels vasculitis characterized by the presence of autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane. Common feature of anti-GBM disease is a combination of rapidly progressive glomerulonephritis and alveolar hemorrhage (pulmonary-renal syndrome). We present a case of atypical disease course in a young male patient who developed alveolar hemorrhage without renal failure. The only symptom of renal involvement was isolated hematuria. Plasmapheresis combined with immunosuppression (cyclophosphamide and corticosteroids) was effective. We present a review of state-of-art data on the pathogenesis and disease course of anti-GBM disease.

scholarly journals Developmental acquisition of basement membrane heterogeneity: type IV collagen in the avian lens capsule.

1983 ◽  
Vol 97 (3) ◽  
pp. 940-943 ◽  
Author(s):  
J M Fitch ◽  
R Mayne ◽  
T F Linsenmayer
Keyword(s):  
Basement Membrane ◽  
Type Iv Collagen ◽  
Lens Capsule ◽  
Basement Membranes ◽  
Developmentally Regulated ◽  
Membrane Heterogeneity ◽  
Domain Specific ◽  
Type Iv ◽  
Anterior Lens Capsule ◽  
Immunohistochemical Analyses

To investigate potential heterogeneity and developmental changes in basement membranes during embryogenesis, we performed immunohistochemical analyses on lens capsules in chicken embryos of different ages using domain-specific monoclonal antibodies against type IV collagen. We found that the capsule of the newly formed lens stained uniformly with antibodies against this component of basement membranes, but with increasing age and differentiation of the lens cells the anterior lens capsule remained brightly fluorescent while staining of the posterior capsule became relatively much less intense. This antero-posterior gradient of anti-type IV collagen antibody reactivity demonstrated that developmentally-regulated changes can occur within a single, continuous basement membrane.

scholarly journals Etanercept-Induced Anti-Glomerular Basement Membrane Disease

2021 ◽  
pp. 292-300
Author(s):  
Saif Al-Chalabi ◽  
Henry H.L. Wu ◽  
Rajkumar Chinnadurai ◽  
Arvind Ponnusamy
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Rapidly Progressive Glomerulonephritis ◽  
Alveolar Haemorrhage ◽  
Small Vessel Vasculitis ◽  
Drug Induced ◽  
Psoriatic Arthropathy ◽  
Tnf Α ◽  
Life Threatening ◽  
Factor Α

Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.

Platelet Interaction With Basement Membrane Proteins

1981 ◽  
Author(s):  
L Balleisen ◽  
J Rauterberg ◽  
J Risteli ◽  
H Rohde ◽  
R Timpl
Keyword(s):  
Membrane Proteins ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Fibrin Clot ◽  
Basement Membranes ◽  
Plastic Substrate ◽  
Acid Extraction ◽  
Clot Retraction ◽  
Type Iv ◽  
Basement Membrane Proteins

Basement membranes consist mainly of two components: non-fibrillar type IV collagen and the non-collagenous glycoprotein laminin (m.w.900.000) which is capable to interact with cell surfaces. The collagenous protein was studied in form of two major fragments comprising together the total mass of the molecule. 7-S collagen which resembles the crosslinking domain of type IV collagen was isolated after collagenase digestion and consisted of four triple helices aligned in a parallel fasion (m.w.360.000). The major triple helical domain of type IV collagen (m.w.450.000) could be obtained by a acid extraction but had lost most of the 7-S domain.Interaction with platelets was examined in aggregation, cell spreading and fibrin clot retraction assays including the determination of malondialdehyde formation. 7-S collagen was the most active component in all three assays. Aggregation was induced by as little as 25 µg/ml and was confirmed by electronmicroscopy. When compared to interstitial collagens, however, 10-20 fold higher amounts of 7-S collagen are required to produce the same effects. Acid extracted type IV collagen possessed virtually no activity. Laminin did not aggregate platelets but promoted strongly their attachment and spreading on a plastic substrate. Thus both basement membrane proteins apparently interact with platelets in different ways via distinct domains of the molecules.

scholarly journals DIABETIC NEPHROPATHY AN OBVIOUS COMPLICATION IN LONG TERM TYPE 1 DIABETES MELLITUS: A CASE STUDY

2017 ◽  
Vol 10 (11) ◽  
pp. 4
Author(s):  
Jahidul Islam Mohammad ◽  
Sridevi Chigurupati ◽  
Azli Shahril Othman ◽  
Muhammad Zahid Iqbal
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Type 1 Diabetes Mellitus ◽  
Case Review ◽  
Type Iv ◽  
Tissue Matrix

  Most overwhelming complications of Type 1 diabetes mellitus patients are responsible for complications related to the microvascular system most likely with kidney. In the kidney, hyperglycemia induced microangiopathy resulting not only thickening of the glomerular capillary basement membrane but also to the proliferation of the mesangial matrix and solidifying of the tubular basement membrane. Several biochemical and pathological, factors are concerned for the development of diabetic renal microangiopathy. These include the glomerular hyperperfusion and hyperfiltration, transformed morphology of podocytes accompanies these basement membrane modifications, Type IV collagen augmented synthesis following the hyperglycemia, and increased expression of tissue matrix metalloproteinase. The aim of this case review is to highlight the recent advances in understanding the pathogenesis, diagnosis, the overview and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.

scholarly journals Anti-glomerular basement membrane disease: an update on subgroups, pathogenesis and therapies

2018 ◽  
Vol 34 (11) ◽  
pp. 1826-1832 ◽  
Author(s):  
Mårten Segelmark ◽  
Thomas Hellmark
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
De Novo ◽  
Correct Diagnosis ◽  
Rapidly Progressive Glomerulonephritis ◽  
Human Leukocyte ◽  
Pulmonary Haemorrhage ◽  
Leukocyte Antigen ◽  
Type Iv

Abstract Most patients with anti-glomerular basement membrane (anti-GBM) disease present with rapidly progressive glomerulonephritis with or without pulmonary haemorrhage; however, there are several variants and vigilance is necessary to make a correct diagnosis. Such variants include overlap with anti-neutrophil cytoplasm antibodies-associated vasculitis and membranous nephropathy as well as anti-GBM occurring de novo after renal transplantation. Moreover, patients can present with isolated pulmonary haemorrhage as well as with negative tests for circulating anti-GBM. Virtually all patients with anti-GBM disease have autoantibodies that react with two discrete epitopes on the α3 chain of type IV collagen. Recent evidence suggests that healthy persons have low-affinity natural antibodies reacting with the same epitopes, but most people are protected from developing disease-causing high-affinity autoantibodies by human leukocyte antigen-dependent regulatory T-cells (Tregs). The α3 chain-derived peptides presented by the HLA-DR15 antigen lack the ability to promote the development of such Tregs. The detection of anti-GBM in circulation using the rapid assay test has led to early diagnosis and improved prognosis. However, our present tools to curb the inflammation and to eliminate the assaulting antibodies are insufficient. Only about one-third of all patients survive with functioning native kidneys. More effective therapies need to be developed; agents that inhibit neutrophil recruitment, deplete B cells and cleave immunoglobulin G (IgG) in vivo may become new weapons in the arsenal to combat anti-GBM disease.

scholarly journals Fcγ Receptor Iib–Deficient Mice Develop Goodpasture's Syndrome upon Immunization with Type IV Collagen

2000 ◽  
Vol 191 (5) ◽  
pp. 899-906 ◽  
Author(s):  
Akira Nakamura ◽  
Takae Yuasa ◽  
Azusa Ujike ◽  
Masao Ono ◽  
Toshihiro Nukiwa ◽  
...  
Keyword(s):  
Rapidly Progressive Glomerulonephritis ◽  
Pulmonary Hemorrhage ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Goodpasture's Syndrome ◽  
Goodpasture’S Syndrome ◽  
Type Iv ◽  
Suitable Animal Model ◽  
And Function

The combination of hemorrhagic pneumonitis and rapidly progressive glomerulonephritis is a characteristic feature of Goodpasture's syndrome (GPS), an autoimmune disease resulting from the interaction of pathogenic anti–collagen type IV (C-IV) antibodies with alveolar and glomerular basement membranes. Lack of a suitable animal model for this fatal disease has hampered both a basic understanding of its etiology and the development of therapeutic strategies. We now report a novel model for GPS using mice deficient in a central regulatory receptor for immunoglobulin (Ig)G antibody expression and function, the type IIB Fc receptor for IgG (FcγRIIB). Mutant mice immunized with bovine C-IV reproducibly develop massive pulmonary hemorrhage with neutrophil and macrophage infiltration and crescentic glomerulonephritis. The distinctive linear, ribbon-like deposition of IgG immune complex seen in GPS was observed along the glomerular and tubulointerstitial membranes of diseased animals. These results highlight the role of FcγRIIB in maintaining tolerance and suggest that it may play a role in the pathogenesis of human GPS.

scholarly journals Formation of basement membranes in the embryonic kidney: an immunohistological study

1981 ◽  
Vol 91 (1) ◽  
pp. 1-10 ◽  
Author(s):  
P Ekblom
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Basement Membranes ◽  
Glomerular Endothelial Cell ◽  
Type Iv ◽  
Endothelial Cell Differentiation ◽  
Inductive Interaction ◽  
Immunohistological Study

Specific antibodies to laminin, type IV collagen, basement-membrane proteoglycan, and fibronectin have been used in immunofluorescence microscopy to study the development of basement membranes of the embryonic kidney. Kidney tubules are known to form from the nephrogenic mesenchyme as a result of an inductive tissue interaction. This involves a change in the composition of the extracellular matrix. The undifferentiated mesenchyme expresses in the composition of the extracellular matrix. The undifferentiated mesenchyme expresses fibronectin but no detectable laminin, type IV collagen, or basement-membrane proteoglycan. During the inductive interaction, basement-membrane specific components (laminin, type IV collagen, basement membrane proteoglycan) become detectable in the induced area, whereas fibronectin is lost. While the differentiation to epithelial cells of the kidney requires an inductive interaction, the development of the vasculature seems to involve an ingrowth of cells which throughout development deposits basement-membrane specific components, as well as fibronectin. These cells form the endothelium and possibly also the mesangium of the glomerulus, and contribute to the formation of the glomerular basement membrane. An analysis of differentiation of the kidney mesenchyme in vitro in the absence of circulation supports these conclusions. Because a continuity with vasculature is required for glomerular endothelial cell differentiation, it is possible that these cells are derived from outside vasculature.

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