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Abstract: PO1799

Low Serum IgG4: A Remarkable Diagnostic Biomarker for IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Tian, Xinyu, Peking University Third Hospital, Beijing, China
  • Wang, Song, Peking University Third Hospital, Beijing, China
  • Deng, Zhenling, Peking University Third Hospital, Beijing, China
  • Wang, Yue, Peking University Third Hospital, Beijing, China
Background

Reports regarding IgG subclasses in IgA nephropathy (IgAN) were scarce. Low serum IgG4 levels in IgAN were noticed in our preliminary experiment. We aim to verify the low IgG4 levels in IgAN and investigate the related immune mechanism.

Methods

Three groups of IgAN patients were enrolled, including the newly diagnosed IgAN-N (n = 58), IgAN-F (n = 28) with a follow-up interval of (19 ± 11) months, and IgAN-10 patients (n = 27) who have been diagnosed over 10 years. Healthy individuals (n = 56) and patients with idiopathic membranous nephropathy (IMN, n = 30) were enrolled as controls. Serum IgG4, IgG, galactose-deficient IgA1 (Gd-IgA1), and urine IgG4 levels were detected by ELISA. The IgG4+B, Th1, and Th2 cells were measured by flow cytometry. Receiver operating characteristic curves and logistic regression analyses were performed to evaluate the diagnostic and predictive abilities of IgG4.

Results

The serum IgG4 levels in IgAN patients with different courses, severity, and outcomes were all significantly lower than those of healthy controls and IMN (all P < 0.001). The cutoff value of IgG4 in differentiating IgAN from healthy individuals and IMN was respectively 0.26mg/ml (sensitivity 98.3%, specificity 82.1%, AUC 0.938, P < 0.0001) and 0.24mg/ml (sensitivity 96.6%, specificity 73.3%, AUC 0.869, P < 0.0001). The risk of IgAN in subjects with low IgG4 levels was 281 times higher than those with normal IgG4 (OR 281.11, 95%CI 34.33 - 2301.97, P < 0.001), and a negative correlation between serum Gd-IgA1 and IgG4 levels was observed in healthy controls (r = -0.240, P = 0.077) instead of IgAN-N patients (r = -0.066, P = 0.629). Similar results were obtained when IgG4/IgG was analyzed in the same patients and controls. The urine IgG4 levels [μg/(g.Cr)] in IgAN-N [798.16 (308.75, 1533.56)] were higher than healthy controls [72.87 (31.51, 201.89), P < 0.001], but were similar to IMN [1153.39 (378.83, 2108.40), P = 0.341]. The IgG4+B/B cells (0.29 ± 0.17 vs. 0.61 ± 0.56, P = 0.017) and Th2/Th (0.54 ± 0.27 vs. 0.87 ± 0.44, P = 0.037) of IgAN were significantly lower than those of healthy controls.

Conclusion

Serum IgG4 levels of IgAN patients are generally low, and the low IgG4 level may be a risk factor for IgAN. Serum IgG4 may be a remarkable diagnostic biomarker for IgAN. Decreased IgG4+B and Th2 cells may contribute to the low IgG4 levels.