Changes in Nephritogenic Serum Galactose-Deficient IgA1 in IgA Nephropathy following Tonsillectomy and Steroid Therapy

Abstract

BackgroundRecent 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.MethodsWe 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.ResultsPatients (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.ConclusionsThe 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.

Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy

“…27 Indeed, we recently showed that Gd-IgA1 was significantly decreased after tonsillectomy in patients with IgAN, who also showed a significant improvement in urinalysis just after tonsillectomy. 26 This study further showed that patients with IgAN with abundant expression of Stalk-1 in tonsillar GC showed more proteinuria and better clinical outcomes after the tonsillectomy, including improvement of proteinuria and decrease of serum Gd-IgA1 levels. These findings suggest that palatine tonsils with overexpression of APRIL may be one of the major delivery source of nephritogenic IgA.…”

“…However, some patients notably showed improved hematuria and serum Gd-IgA1 levels after steroid pulse therapy after the tonsillectomy compared with just after tonsillectomy, suggesting that Gd-IgA1-producing cells may also be localized outside the tonsils. 26 Recent data have revealed that some of the NALT-derived and -activated B cells and even tonsillar B cells can migrate from inductive mucosal sites to systemic effector sites, including bone marrow, through guiding adhesion molecules and chemokine/chemokine receptors. 52,53 In addition, our recent study revealed that IgA1 secreted by Epstein-Barr virusimmortalized B cells from the peripheral blood of patients with IgAN was mostly polymeric with Gd sialylated O-glycans.…”

The efficacy of tonsillectomy on clinical remission and relapse in patients with IgA nephropathy: a randomized controlled trial

“…Nakata et al found that serum GdIgA1 levels decreased by 59% after tonsillectomy, thus indicating that the palatine tonsils are probably a major sites of GdIgA1-producing cells. 23 In fact, Japanese Society of Nephrology clinical guidelines for IgAN suggested tonsillectomy plus steroid pulse therapy to achieve early CR in 2011. 24 Tonsillectomy may delay the progression of IgAN especially in patients with macrohematuria.…”

Efficacy of triptolide on the apoptosis of tonsillar mononuclear cells from patients with IgA nephropathy

“…18 Observations have suggested that tonsillectomy could reduce the incidence of microhematuria and proteinuria in patients with normal renal function and mild proteinuria, 19,20 as well as the level of aberrantly galactosylated IgA1 in patients with IgAN. 21,22 However, the definitive pathogenic mechanism of tonsillitis in IgAN is still debated. We hypothesized that the overactive state of the tonsils and tonsillitis-mediated inhibition of immune tolerance might facilitate IgAN.…”