Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?

Abstract

The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/β1, p = 0.039; LPM7/β5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.

The mucosa–kidney axis in IgA nephropathy

“…Tonsillectomy combined with steroid pulse therapy induced a 10% greater decrease in proteinuria than steroid pulse therapy alone, but this decrease was of marginal statistical significance, and whether it would lead to a subsequent beneficial effect on renal function is unclear. Consistent with the Japanese trial, a comparison of tonsillectomized patients with IgAN and non-operated matched controls with IgAN assessed in a study performed by the European VALIGA network failed to show any effects of tonsillectomy on circulating markers of innate immunity, ubiquitin-proteasome pathways and the pro-oxidative milieu 87 , or on clinical outcome 88 .…”

Long‐term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy

“…In contrast, outside of Japan, the efficacy of TMP in IgAN still remains controversial . Feehally et al .…”

“…In contrast, outside of Japan, the efficacy of TMP in IgAN still remains controversial. 36,37 Feehally et al 36 reported that there was no significant correlation between tonsillectomy and renal function decline in the European validation study of the Oxford classification of IgAN. The reason for this discrepancy is unclear.…”

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.…”