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

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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.

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Authors and Affiliations

  1. Division of Otorhinolaryngology, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy

    Luca Vergano & Roberto Albera

  2. Nephrology, Dialysis and Transplantation Children Unit, University Hospital Città della Salute e della Scienza di Torino, Corso Spezia 60, 10126, Turin, Italy

    Elisa Loiacono, Rosanna Coppo, Roberta Camilla, Licia Peruzzi, Alessandro Amore, Maria Elena Donadio & Federica Chiale

  3. Nephrology, Dialysis and Transplantation Unit, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy

    Alberto Boido & Filippo Mariano

  4. Department of Biomedical Sciences and Human Oncology, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy

    Gianna Mazzucco

  5. Division of Nephrology, Dialysis and Transplantation, University Hospital Spedali Civili di Brescia, Brescia, Italy

    Sara Ravera & Giovanni Cancarini

  6. University Hospital Policlinico di Modena, Modena, Italy

    Riccardo Magistroni

  7. G.Bosco Hospital, Turin, Italy

    Giulietta Beltrame & Cristiana Rollino

  8. Division of Nephrology and Transplantation, Novara Maggiore University Hospital, Novara, Italy

    Piero Stratta & Marco Quaglia

  9. Ospedale degli Infermi, Biella, Italy

    Roberto Bergia & Raffaella Cravero

  10. Nephrology and Dialysis, Borgomanero Hospital, Borgomanero, Italy

    Stefano Cusinato & Luisa Benozzi

  11. Ciriè Hospital, Cirié, Italy

    Silvana Savoldi & Carola Licata

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  1. Luca Vergano
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  2. Elisa Loiacono
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Correspondence to Licia Peruzzi.

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Vergano, L., Loiacono, E., Albera, R. et al. Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?. J Nephrol 28, 51–58 (2015). https://doi.org/10.1007/s40620-014-0086-8

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  • DOI: https://doi.org/10.1007/s40620-014-0086-8

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