Accuracy of Anti-GBM Antibodies in Diagnosing Anti-Glomerular Basement Membrane Disease: A Systematic Review and Meta-Analysis

Abstract

<b><i>Background:</i></b> The sensitivity and specificity of anti-glomerular basement membrane (GBM) antibodies have not been systematically analyzed. In this systematic review, we aimed to evaluate the diagnostic accuracy of anti-GBM antibodies for anti-GBM disease. <b><i>Summary:</i></b> Potential studies were searched using MEDLINE, Embase, the Cochrane Library, and the International Clinical Trials Registry Platform based on the index test and target condition. The inclusion criteria were prospective or retrospective cohort studies or case-control studies assessing the sensitivity and specificity of anti-GBM antibodies, and the reference standard was clinical diagnosis including biopsy results. The exclusion criteria were review articles, case reports, animal studies, and in vitro studies. Quality assessment was conducted based on the Quality Assessment of Diagnostic Accuracy Studies-2. The pooled estimates of sensitivity and specificity were calculated using a bivariate random-effects model. The overall quality was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation. Six studies (1,691 patients) and 11 index tests were included in our systematic review. A high risk of bias and concerns regarding the applicability of patient selection were noted because of the case-control design in 67% of the included studies. The pooled sensitivity and specificity were 93% (95% CI: 84–97%) and 97% (95% CI: 94–99%), respectively. The certainty of evidence was low because of the high risk of bias and indirectness. <b><i>Key Messages:</i></b> Anti-GBM antibodies may exhibit high sensitivity and specificity in the diagnosis of anti-GBM disease. Further cohort studies are needed to confirm their precise diagnostic accuracy and compare diagnostic accuracies among different immunoassays.

Anti-GBM disease with positive serum anti-GBM antibodies but negative IgG deposition: A case report

“…10 A systematic review and meta-analysis reported that the sensitivity and specificity of anti-GBM antibody detection in diagnosing anti-GBM disease were 93% and 97%, respectively. 11 In another study, Qu et al 12 claimed that IgG deposition was detected among all patients with anti-GBM disease. Large biopsy series suggest that 95% of patients will have evidence of crescent formation on kidney biopsy, and that in 80% of patients >50% of glomeruli will be affected.…”

Serodiagnosis of Anti-glomerular Basement Membrane Disease Using a Newly Developed Chemiluminescence Immunoassay

“…Due to the retrospective character of this study, no further investigations about clinical and serological manifestations in these patients are feasible. Future studies could provide further insights and moreover address the need for comparisons among different immunoassays ( 8 ). In addition, limitations of the present study could be addressed, for example with regard to sample selection.…”

“…In routine diagnostics, this antigen is thus utilized as substrate by various immunoassay formats, most notably indirect immunofluorescence tests and ELISA, for the detection of anti-GBM autoantibodies to support diagnosis of anti-GBM disease. A recent literature-based meta-analysis confirmed the potential high sensitivity and specificity in the diagnosis of anti-GBM disease ( 8 ).…”

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) for life-threatening isolated pulmonary anti-GBM disease

“…The pathogenic anti-GBM antibodies are usually IgG class, but a few cases are caused by IgA or IgG4 alone [ 5 , 6 ]. The sensitivity and specificity of anti-GBM antibodies were 93% and 97%, so they showed low false-negative and high true positive rate [ 7 ]. At another point of view, 32% of all anti-GBM positive samples have detectable ANCA, and 5% of all ANCA-positive serum samples also have detectable anti-GBM antibodies, but the mechanism is unclarified [ 8 ].…”