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.

Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

“…Treatment of patients with IgAN has included several approaches that reduce circulating levels of Gd-IgA1. Tonsillectomy has been widely accepted in Japan [ 86 , 87 , 88 , 89 , 90 ]. Gd-IgA1 production by IgA1-secreting cells in tonsils is related to abnormalities in the expression of glycosyltransferase genes associated with core 1 O -glycosylation [ 91 ].…”

Mucosal Immune System Dysregulation in the Pathogenesis of IgA Nephropathy

“…It has also been reported that, in patients with IgAN, the T-cell area in the tonsils is significantly expanded and the ratio of IgA/IgG-producing cells is high compared with that in patients with chronic tonsillitis. Furthermore, tonsillectomy performed at 1 year after kidney transplantation significantly decreased the level of serum Gd-IgA1 and the recurrence rate of histological IgAN after kidney transplantation [ 70 ]. On the bases of these findings, serum Gd-IgA1 derived from the tonsillar B cells likely plays an important role in the pathogenesis of IgAN.…”

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

“…Several studies suggest strategies as a part of prophylaxis to suppress IgAN recurrence, although no established induction therapy exists. As a prevention of IgAN recurrence, the Jikei group adopted elective tonsillectomy 1 year after renal transplantation and examined the relationship between tonsillectomy and serum GdIgA1 and GdIgA1 deposition in tonsils and kidneys [63]. They revealed that elective tonsillectomy reduced the rates of IgAN recurrence, coupled with decreased immunoreactivities of GdIgA1.…”

“…Next, our concern is therapeutic modalities available in IgAN recurrence. Although there is no specific guideline for renal transplant recipients, many institutions basically follow native IgAN treatments consisting of steroid pulse [65], rituximab, tonsillectomy [63], and elimination of other exacerbating factors. A simple observation strategy often takes place for many PR cases, especially in elderly recipients, combined with lifestyle guidance.…”