Abstract: PUB200
Diagnostic Value of IgG-Antigalactose-Deficient IgA in IgAN or IgA Vasculitis
Session Information
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Nachman, Patrick H., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Allam, Krishna C, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Rabi, Salma, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Theis-Mahon, Nicole, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Lardinois, Olivier, unaffiliated, Chapel Hill, North Carolina, United States
Background
Elevated levels of galactose-deficient IgA1 (GdIgA1) and the formation of IgG antibodies against GdIgA1 (IgG-antiGdIgA1) are key elements in the pathogenesis of IgA nephropathy (IgAN). However the diagnostic utility of circulating IgG-antiGdIgA1 remains uncertain. We conducted a systematic review of the diagnostic performance of IgG-antiGdIgA1 in patients with IgAN or IgA vasculitis (IgAV) compared to healthy (HC) or disease (DC) controls.
Methods
This PRISMA-compliant systematic review searched MEDLINE, Embase, Scopus, Web of Science, and CENTRAL (to 1/2025), combining terms for IgAN, IgAV, Gd-IgA1, autoantibodies, and diagnosis. Studies were included if they evaluated the diagnostic accuracy of IgG-antiGdIgA1 in IgAN/V vs HC or DC, reported relevant statistical analyses, and had a sample size ≥ 20. Data on study design, population, test assays, and diagnostic performance were systematically extracted.
Results
The database searches identified 9585 publications, of which 3908 were duplicates. Of the remaining 5677 articles, 79 were retained for full-text review, of which 71 were excluded due to wrong study design, no anti-GdIgA1 measurements, small sample size, or no diagnostic statistics. The remaining 8 publications included 519 patients with IgAN/V, 216 HC, and 126 DC. Six studies reported clinical data, but only one adjusted for confounders. Author network analysis identified only 2 independent groups. The table summarizes the findings of the 5 studies that reported diagnostic performance of IgG-antiGdIgA.
Conclusion
The diagnostic value of IgG-antiGdIgA1 is based on few studies by inter-related investigators, and varied results. The use of myeloma-derived GdIgA1 as the antigen further limits the tests' reproducibility for diagnosis. Additional independent studies in separate cohorts are necessary to establish the diagnostic value of IgG-antiGdIgA1.
| Study | IgAN/HC/DC (N) | Antigen | AUC | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | Cutoff |
| Placzek 2018 | 135*/106*/- | myeloma GdIgA1 Fab** | - | 87 | 99 | - | - | 1.53 U (2 SD > HC mean) |
| Suzuki 2009 | 60/40/20 | myeloma GdIgA1 | 0.96 | 88 | 95 | - | - | - |
| Yanagawa 2014 | 135*/106*/79 vs HC | myeloma GdIgA1 Fab** | 0.96 | 89 | 92 | 92 | 89 | 1.48 U (90th% HC) |
| vs CKD | 0.97 | 89 | 96 | 96 | 90 | |||
| vs immune-mediated CKD | 0.81 | 85 | 67 | 72 | 82 | |||
| Berthoux 2012 | 97/60(HC+DC) | myeloma GdIgA1 Fab** | 0.63 | - | - | - | - | 1.33 OD (Normalized) |
| Berthoux 2017 | R+ (n=34) vs. R– (n=62) | myeloma GdIgA1 Fab** | 0.62 | 68 | 63 | 48 | 76 | 1.53 OD (Normalized) |
AUC = area under curve; R= post-transplant recurrence; OD= Optical Density; Fab = Fab fragment; *same patients. **same myeloma protein