Rituximab for Anti-Glomerular Basement Membrane Disease.
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ABSTRACT:
SUBMITTER: Jain R
PROVIDER: S-EPMC6451084 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Rituximab for Anti-Glomerular Basement Membrane Disease.
Jain Rashmi R Dgheim Hanna H Bomback Andrew S AS
Kidney international reports 20181217 4
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Project description: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.
| S-EPMC10239794 | biostudies-literature
Project description: Not available
| S-EPMC10166737 | biostudies-literature
Project description:IntroductionIn 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.MethodsCirculating 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.ResultsCirculating 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.ConclusionCirculating 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.
| S-EPMC10658233 | biostudies-literature
Project description:BackgroundAnti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic necrotizing glomerulonephritis, with linear deposits of immunoglobulin G (IgG) in the GBM. Classic anti-GBM disease is clinically associated with rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Some patients have a better renal prognosis and milder symptoms than those with classic anti-GBM disease, which is termed atypical anti-GBM disease.Case presentationA 43-year-old Japanese woman was admitted to our hospital complaining of hematuria that had persisted for more than one month. Serological examination revealed negativity for anti-nuclear, anti-neutrophilic cytoplasmic, and anti-GBM antibodies. However, renal biopsy showed cellular crescents. Immunofluorescence revealed strong diffuse linear capillary loop staining for IgG. An indirect immunofluorescence antibody method was performed by applying the patient serum to normal kidney tissue to confirm the presence of autoantibodies binding to the GBM. Using this method, anti-GBM antibodies were detected. The patient was treated with high-dose steroids, cyclophosphamide, and plasma exchange. Aggressive treatment resolved proteinuria and hematuria and improved renal function.ConclusionsRenal biopsy is crucial in the diagnosis of anti-GBM disease, especially when serological tests are negative. Accurately identifying the presence of anti-GBM disease is important to initiate optimal treatment.
| S-EPMC9675149 | biostudies-literature
Project description:Anti-glomerular basement membrane (Anti-GBM) disease is a severe form of glomerulonephritis (GN) that predominantly impacts individuals aged 20 to 70. It arises from the presence of circulating antibodies that specifically target an antigen inherent to the basement membranes of glomerular and alveolar structures. A unique subset within this category is termed atypical anti-GBM disease. In this variant, a distinctive feature is the widespread linear staining of the glomerular basement membrane (GBM) by IgG observed through immunofluorescence microscopy, with the notable absence of anti-GBM antibodies in the patient's serum. Here, we present an unusual case involving a 65-year-old female patient who sought medical attention due to rapidly progressing renal failure. The initial management included six hemodialysis sessions. Following a kidney biopsy, the diagnosis revealed a sclerosed phase of diffuse crescentic glomerulonephritis, attributed to atypical anti-GBM disease. Given the presence of diffuse crescents on the kidney biopsy, the medical team opted for an aggressive treatment regimen, commencing with intravenous methylprednisolone, followed by oral cyclophosphamide and oral prednisolone. Plasmapheresis was also recommended as part of the treatment plan, although it did not materialize due to the family's reluctance. Despite exhaustive efforts, the renal failure exhibited no signs of improvement, leading to the patient's discharge with a plan for ongoing maintenance hemodialysis. It is crucial to emphasize the pivotal role of immunosuppressive medications in managing this condition, as they play a critical role in preventing antibody formation and subsequent hypersynthesis that can exacerbate the disease.
| S-EPMC10731130 | biostudies-literature
Project description: Not available
| S-EPMC8484114 | biostudies-literature
Project description:A 46-year-old female presented with a chief complaint of fatigue and intermittent painless gross hematuria for one month. The patient was fluid overloaded on physical examination and noted to be in acute renal failure with a serum creatinine of 10.8 mg/dL. The patient was emergently started on hemodialysis. Serologies were negative for antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibody (ANCA), and anti-glomerular basement membrane (anti-GBM) antibody. However, renal biopsy revealed 90% glomerular involvement by temporally heterogeneous crescents ranging from cellular to fibrous. Immunofluorescence studies revealed strong, linear glomerular capillary wall staining for immunoglobulin G (IgG). Although the patient was treated with pulse dose steroids and cyclophosphamide, the patient ultimately developed infectious complications from immunosuppression, and treatment was terminated. This case highlights the atypical presentation of anti-GBM disease diagnosed based on renal biopsy with negative serologies. Although rare, the possibility of atypical anti-GBM antibodies which are not detected by standard commercial assays should be considered in such cases.
| S-EPMC6603348 | biostudies-literature
Project description:An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome.We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties.Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival.To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.
| S-EPMC4974897 | biostudies-other
Project description:Background and objectivesApproximately 20%-30% of patients with anti-glomerular basement membrane disease present coexisting anti-myeloperoxidase (MPO) autoantibodies. We previously showed the recognition of a linear fragment of the MPO heavy chain N-terminus ((1)H, MPO279-409) in plasma from most double-positive patients. Herein, we investigated the frequency of autoantibodies against overlapping (1)H-derived linear peptides in plasma from patients with anti-glomerular basement membrane disease.Design, setting, participants, & measurementsWe synthesized 13 overlapping linear peptides ((1)H-1 to (1)H-13) covering MPO279-409. We retrospectively collected plasma samples from 67 patients with anti-glomerular basement membrane disease from 1996 to 2012, and we screened them for IgG autoantibodies by ELISA using intact human MPO and the overlapping peptides as antigens, and we further investigated the clinical significance. Autoantibody binding to the linear MPO structure was confirmed by Western blotting.ResultsWe followed up the 67 patients until 2015, with a median follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the 67 patients with follow-up data. Plasma from 23.9% (16) of the patients recognized intact human MPO, whereas 62.7% (42) plasma samples recognized MPO279-409 linear peptides. Of the 13 linear peptides, (1)H-4 (44.8%, 30 patients) and (1)H-12 (40.3%, 27 patients) exhibited the highest recognition frequencies. Patients with autoantibodies against (1)H-11 or (1)H-12 (MPO371-400) were older (46.1±18.8 versus 34.1±16.6 years; P<0.01), had higher serum creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a higher probability of progressing to ESRD; however, multivariate Cox regression analysis showed that (1)H-11 or 12 reaction was not an independent risk factor for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8; P=0.19).ConclusionsAutoantibodies against linear peptides of MPO can be detected in the majority of patients with anti-glomerular basement membrane disease, and several are associated with disease severity. The potential common pathogenic mechanism between anti-glomerular basement membrane antibodies and anti-MPO autoantibodies in anti-glomerular basement membrane disease requires further investigation.
| S-EPMC4822661 | biostudies-literature
Project description:Anti-glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.
| S-EPMC6877440 | biostudies-literature