Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation

Abstract

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.

Keywords: IgA nephropathy; galactose-deficient IgA1; kidney transplantation; recurrent glomerulonephritis; tonsillectomy.

Figure 1

Subject enrolment flow chart. From May 1988 to June 2014, 36 patients with biopsy-proven IgA nephropathy (IgAN) underwent kidney transplantation in our hospital. Among the 36 patients, we excluded those with the following: tonsillectomy (TE) performed before transplantation, no clinical data available, IgAN with vasculitis, a second allograft, and graft loss due to lack of drug compliance. In total, 27 patients were included in this study. Among them, nine underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE after transplantation (group 2).

Figure 2

Log-rank test of histological IgAN recurrence in group 1 (red line) and group 2 (blue line).

Figure 3

Serum Gd-IgA1 level. Serum Gd-IgA1 levels decreased after TE in group 1 (a,b) but remained stable or gradually increased in group 2 (c). Serum Gd-IgA1 levels gradually increased before TE and decreased thereafter (d).

Figure 4

Group 1 (without IgAN recurrence). IgA and Gd-IgA1 were localized in the mantle zone of tonsils. No mesangial deposits of IgA and Gd-IgA1 were observed in the 0-h and 5-year biopsies (allograft biopsies, ×200; tonsils, ×40).

Figure 5

Patient 1 of group 1 (with IgAN recurrence). IgA and Gd-IgA1 deposits were observed in both the mantle zone and at the germinal center of tonsils. Mesangial deposits of IgA and Gd-IgA1 were observed in the 3-year biopsies (allograft biopsies, ×200; tonsils, ×40).

Figure 6

Patient eight of group 2 (with IgAN recurrence). Mesangial IgA and Gd-IgA1 deposition did not increase after TE. IgA and Gd-IgA1 were deposited at the geminal center and in the mantle zone of tonsils (allograft biopsies, ×200; tonsils, ×40).

Figure 7

Comparison of tonsils from patients with sleep apnoea syndrome (SAS) and native IgAN. Deposition of IgA and Gd-IgA1 at the germinal center was greater in recurrent cases (magnification, ×40).