Changes in nephritogenic serum galactose-deficient IgA1 in IgA nephropathy following tonsillectomy and steroid therapy

Abstract

Background: Recent studies have shown that galactose-deficient IgA1 (GdIgA1) has an important role in the pathogenesis of IgA nephropathy (IgAN). Although emerging data suggest that serum GdIgA1 can be a useful non-invasive IgAN biomarker, the localization of nephritogenic GdIgA1-producing B cells remains unclear. Recent clinical and experimental studies indicate that immune activation tonsillar toll-like receptor (TLR) 9 may be involved in the pathogenesis of IgAN. Here we assessed the possibility of GdIgA1 production in the palatine tonsils in IgAN patients.

Methods: We assessed changes in serum GdIgA1 levels in IgAN patients with clinical remission of hematuria and proteinuria following combined tonsillectomy and steroid pulse therapy. Further, the association between clinical outcome and tonsillar TLR9 expression was evaluated.

Results: Patients (n = 37) were divided into two groups according to therapy response. In one group, serum GdIgA1 levels decreased after tonsillectomy (59%) alone, whereas in the other group most levels only decreased after the addition of steroid pulse therapy to tonsillectomy (41%). The former group showed significantly higher tonsillar TLR9 expression and better improvement in hematuria immediately after tonsillectomy than the latter group.

Conclusions: The present study indicates that the palatine tonsils are probably a major sites of GdIgA1-producing cells. However, in some patients these cells may propagate to other lymphoid organs, which may partially explain the different responses observed to tonsillectomy alone. These findings help to clarify some of the clinical observations in the management of IgAN, and may highlight future directions for research.

Figure 1. Classification of patients with immunoglobulin A nephropathy (IgAN) based on therapy response.

Group A exhibited reduced serum galactose-deficient IgA1 (GdIgA1) levels after tonsillectomy alone. Group B showed no response to tonsillectomy alone. Group B patients were further subdivided into those exhibiting reduced GdIgA1 levels after initiation of steroid therapy (group B1) and those not showing a reduction (group B2). The cut-off level for a reduction in GdIgA1 levels was 1 (after/before tonsillectomy or after the first steroid pulse therapy session/after tonsillectomy, <1 indicated a reduction; ≥1 indicated no reduction).

Figure 2. Comparison between groups A and B before and after tonsillectomy.

(A) The rate of change in hematuria was <1 in group A and was significantly lower than that in group B. (B) Tonsillar TLR9 expression in group A was significantly higher than that in group B. (C) The rate of change in proteinuria before and after tonsillectomy was not significantly different between groups A and B. (D) The rate of change in serum Cr before and after tonsillectomy was not significantly different between groups A and B.

Figure 3. Comparison between groups B1 and B2 before and after the first steroid pulse therapy session.

(A) An improvement in hematuria was observed in group B1, but not in group B2. The rate of change in hematuria in group B1 was significantly lower than that in group B2. (B) The rate of change in proteinuria before and after the first steroid pulse therapy session was not significantly different between groups B1 and B2. (C) The rate of change in serum creatinine before and after the first steroid pulse therapy session was not significantly different between groups B1 and B2.