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-Immunofluorescence microscopy: intense linear staining along the glomerular capillary loops for IgA (×400).
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Context 1
... biopsy was performed. Light microscopy demonstrated focal necrotizing crescentic glomerulonephritis with cellular and fibrous crescents (Fig. 1). 40% of glomeruli were globally sclerotic. Immunofluorescence microscopy demonstrated linear (2+) staining along the glomerular capillary loops for IgA (Fig. 2) along with weak linear staining for IgG, anti-kappa and anti-lambda antibodies. Interstitial fibrosis and tubular atrophy occupied 40% of renal parenchyma. By electron microscopy there were no immune complex-type deposits. The findings were consistent with IgA-mediated anti-GBM disease. The patient had 12 plasma exchanges during a 1 ...
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Antiglomerular basement membrane disease (anti-GBM) is an unusual cause of glomerulonephritis. Patients usually present with rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. The diagnosis is based on linear deposits of IgG along the GBM and the presence of anti-GBM antibodies. However, cases with atypical anti-GBM diseas...
Classic antiglomerular basement membrane (anti-GBM) disease is an exceedingly rare but extremely aggressive form of glomerulonephritis, typically caused by autoantibodies directed against cryptic, conformational epitopes within the noncollagenous domain of the type IV collagen alpha-3 subunit. Pathologic diagnosis is established by the presence of...
Citations
... Due to its rarity, the incidence of the disease is uncertain; studies point to an incidence of less than 1 case/million inhabitants/year in Europe, and it is even rarer in African populations (1). It shows a bimodal age distribution, with peaks in incidence in the third and sixth decades; in younger patients, there is a slight predominance of cases in men and pulmonary involvement is more frequent, while there is a predominance of cases in women and more cases of isolated glomerulonephritis in the older population (1)(2)(3)(4)(5). ...
... The diagnosis of anti-GBM disease consists of identifying the pathogenic autoantibodies, either in serum and/or deposited in the tissues. Immunoassay serological tests may not detect IgA class anti-GBM antibodies, emphasizing the importance of renal biopsy in diagnosing the pathology (1)(2)(3)5,7,12,13). ...
... The predictors of worse renal outcomes include the severity of renal dysfunction at disease presentation, especially if the serum creatinine level X5.7 mg/dL (503.9 mmol/L), the ratio of glomeruli affected by crescents, and oligoanuria at presentation. Kidney transplantation is a therapeutic option if anti-GBM antibodies are negative for at least 6 months (1)(2)(3)7,8,14). ...
Anti-glomerular basement membrane (GBM) disease is a rare and severe vasculitis that affects the glomerular and pulmonary capillaries and has an incidence of less than 2 cases per million individuals per year. Anti-GBM disease is mediated by autoantibodies against the α3 chain of type IV collagen. In the majority of cases, the autoantibodies are of the immunoglobulin G (IgG) class, with rare cases being mediated by immunoglobulin M (IgM) or immunoglobulin A (IgA); there are less than 15 IgA-mediated cases reported in the literature worldwide. The classic form of this disease manifests with rapidly progressive glomerulonephritis (RPGN), with or without pulmonary hemorrhage, and the diagnosis consists of identifying high titers of autoantibodies in the serum and/or deposited in the tissues. IgA antibodies are not identified in routine immunoassay tests, and renal biopsy with immunofluorescence is essential for diagnosis. We present a case of RPGN due to anti-GBM disease with linear IgA deposition, whose diagnosis was made exclusively by renal biopsy and with an unfavorable prognosis.
... In most cases, the causative antibody is IgG [2,3]. Rarely, however, anti-GBM disease is mediated by immunoglobulin A (IgA) or immunolgobulin M (IgM) antibodies [4][5][6][7]. Here, we describe a new case of anti-GBM disease mediated by immunolgobulin G (IgG) and IgA. ...
Background
Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition responsible for rapidly progressive glomerulonephritis. This disease is usually mediated by IgG autoantibodies against the noncollagenous domain of the α3(IV) collagen chain. In rare cases, IgA or IgM anti-GBM antibodies are involved. This raises the question of whether there are different types of antibody-mediated anti-GBM disease at the same time.
Case report
A 37-year-old woman with anti-GBM disease mediated by IgG and IgA. The patient developed rapidly progressive glomerulonephritis with nephrotic syndrome. Indirect immunofluorescence analysis indicated the presence of IgG and IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoadsorbent assay and Western blotting as the α3(IV) collagen chain. After plasmapheresis and immunotherapy (steroids and cyclophosphamide), much improved the massive proteinuria and renal function. Follow up to date, she had normal renal function without proteinuria.
Conclusions
This is the first case report of anti-GBM disease mediated by IgG and IgA. If the clinical presentation and histopathological findings are suggestive of atypical anti-GBM disease, alternative laboratory tests such as Western blotting analysis can be used to confirm the diagnosis.
Introduction
In some cases, immunoglobulin (IgA)-mediated antiglomerular basement membrane (anti-GBM) disease has been reported. Whether circulating IgA anti-GBM antibodies affect the clinico-pathologic characteristics and outcome of typical anti-GBM disease deserves further study.
Methods
Circulating IgA anti-α3(IV)NC1 antibodies were examined by enzyme-linked immunosorbent assay (ELISA) using recombinant human α3(IV)NC1 as solid phase antigens in 107 patients with anti-GBM disease and 115 controls. Clinical, pathological, and follow-up data of patients were retrospectively analyzed.
Results
Circulating IgA anti-α3(IV)NC1 antibodies were found in 18.7% (20/107) of patients with anti-GBM disease but were not detected in healthy controls or in patients with other glomerular diseases. The positivity of circulating IgA anti-α3(IV)NC1 antibodies was not associated with whether the patient was with combined IgA nephropathy or other glomerulonephritis. Kidney immunofluorescence showed no statistical difference in IgA deposition between patients with circulating IgA anti-α3(IV)NC1 antibodies and patients without (30.0% vs. 40.4%, P = 0.725). The titers of circulating immunoglobulin G (IgG) anti-α3(IV)NC1 antibodies in patients with circulating IgA anti-α3(IV)NC1 antibodies were significantly higher than those without (200 [183.3, 200] vs. 161 [85.5, 200] U/ml, P = 0.005). There were no significant differences in kidney outcome and mortality between the 2 groups.
Conclusion
Circulating IgA anti-α3(IV)NC1 antibodies occurred in 18.7% (20/107) of patients with anti-GBM in our center and were specific to anti-GBM disease. Patients with circulating IgA anti-α3(IV)NC1 antibodies showed a higher levels of serum IgG anti-α3(IV)NC1 antibodies than those without.
Atypical anti-glomerular basement membrane (anti-GBM) disease is characterized by linear immunoglobulin G (IgG) deposition along the GBM without circulating IgG anti-GBM antibodies. Compared to classic anti-GBM disease, atypical anti-GBM disease tends to be milder with a more indolent course in certain cases. Moreover, pathologic disease pattern is much more heterogenous in atypical anti-GBM disease than in the classic type, which is uniformly characterized by diffuse crescentic and necrotizing glomerulonephritis. Although there is no single well-established target antigen in atypical anti-GBM disease, the target antigen (within the GBM) and the autoantibody type are hypothesized to be different from the classic type. Some patients have the same antigen as the Goodpasture antigen that are detected only by a highly sensitive technique (biosensor analysis). Some cases of atypical anti-GBM disease have autoantibodies of a different subclass restriction like IgG4, or of monoclonal nature. Antibodies targeting antigen/epitope structure other than the Goodpasture antigen can be detected using modified assays in some cases. Patients with IgA- and IgM-mediated anti-GBM disease are known to have negative circulating antibodies because conventional assays do not detect these classes of antibodies. A significant proportion of cases with atypical anti-GBM disease do not have any identifiable antibodies despite extensive evaluation. Nevertheless, extensive evaluation of atypical autoantibodies using modified assays and sensitive techniques should be attempted, if feasible. This review summarizes the recent literature on atypical anti-GBM disease.
