Tonsillectomy timing is vital for IgAN treatment 

IgA Nephropathy (IgAN), or Berger’s disease, is a kidney disorder characterized by the deposition of Immunoglobulin A (IgA) antibodies in the glomeruli, leading to inflammation and potential kidney failure. Recent studies have highlighted the autoimmune nature of IgAN and the significant role of the tonsils in its development and treatment.

The Autoimmune Nature of IgAN

IgAN is increasingly recognized as an autoimmune condition. The disease involves the production of aberrant IgA1 molecules, which form immune complexes that deposit in the kidneys, triggering inflammation. This process is believed to be initiated by mucosal immune responses, particularly in the tonsils, which are key sites for IgA production.

Tonsillitis as a Trigger

Chronic or recurrent tonsillitis has been implicated as a potential trigger for IgAN. A nationwide Japanese cohort study involving over 4 million individuals found that chronic tonsillitis was associated with a 2.7-fold increased risk of developing IgAN. This suggests that persistent inflammation in the tonsils may contribute to the aberrant immune responses seen in IgAN patients (AJKD, 2024).

Tonsillectomy: A Therapeutic Intervention

Given the tonsils’ role in IgAN, tonsillectomy has been explored as a treatment option. In Japan, tonsillectomy combined with steroid pulse therapy (SPT) has become a standard approach for managing IgAN. A study in the International Journal of Molecular Sciences demonstrated that this combination therapy led to histological improvements in both tonsillar and glomerular lesions, highlighting the interconnectedness of these tissues (IJMS, 2024).

A retrospective study further indicated that tonsillectomy alone can be beneficial in reducing proteinuria and preserving renal function in IgAN patients, particularly when performed early in the disease course (PeerJ, 2022).

Tonsillectomy vs. Steroid Pulse Therapy: A Strategic Choice

A common treatment in Japan and increasingly discussed worldwide is a combination of tonsillectomy with steroid pulse therapy (SPT). The rationale stems from the observation that tonsils are a primary site of aberrant IgA1 production in IgA Nephropathy. While tonsillectomy removes the glandular source of pathogenic IgA, steroid pulses aim to suppress the immune system’s production of IgA systemically.

However, it is important to understand that steroid pulse therapy is itself an IgA production inhibitor—a pharmacological analogue to the surgical removal of the IgA-producing tonsils. When both are used simultaneously, the treatments may be functionally duplicative in their mechanism of action.

Furthermore, the side effects of steroid pulse therapy are significant and frequently challenging. These include:

• Weight gain
• Mood and sleep disturbances
• Increased infection risk
• Osteoporosis
• Hyperglycemia and increased risk of diabetes
• Cataracts and glaucoma
• Adrenal suppression

Because of these well-documented complications, particularly in long-term use, it is both rational and compassionate to sequence treatment in a way that minimizes unnecessary exposure to systemic immunosuppressants. Many clinicians and patients now advocate for an approach where tonsillectomy is the first-line intervention. If the patient experiences resolution or significant improvement of IgAN markers (such as reduced proteinuria or stabilized GFR), the use of steroid pulse therapy may be avoided altogether.

Only if tonsillectomy proves insufficient in halting disease progression or inducing remission should steroid pulse therapy be considered as a secondary treatment option. This patient-first sequencing could improve quality of life, reduce treatment burden, and still allow access to steroid therapy if necessary.

Tonsils in Other Autoimmune Disorders

The influence of tonsillar immune activity isn’t limited to IgAN. Case reports and small clinical studies suggest that tonsillectomy may modulate immune responses in other autoimmune conditions. For instance, in a rare case of anti-SRP myopathy combined with IgAN, a patient showed substantial therapeutic improvement after undergoing tonsillectomy (Frontiers in Immunology, 2020). This supports the hypothesis that tonsils may serve as a persistent source of aberrant immune signaling in autoimmune disease.

Another striking example is Palmoplantar Pustulosis (PPP), a rare and painful autoimmune skin condition affecting the palms and soles. Numerous studies, particularly from Japan, have shown that tonsillectomy results in complete and permanent remission of PPP in a significant number of patients. This finding strengthens the case that the tonsils act as chronic foci of immune dysregulation in various autoimmune disorders.

Tonsillectomy and Asthma: Exploring the Dramatic Effectivness

Emerging research also suggests that tonsillectomy and adenoidectomy (adenotonsillectomy) may benefit children with asthma, particularly those with enlarged tonsils or coexisting obstructive sleep apnea. In a study of over 13,000 children with asthma, adenotonsillectomy led to a 30–38% reduction in asthma-related emergency room visits, hospitalizations, and medication usage (PLOS Medicine).

Other studies have observed improved asthma control test (ACT) scores and reductions in inflammatory biomarkers following surgery. Importantly, these findings reinforce the principle that removing chronically inflamed, IgA-producing lymphoid tissue can relieve systemic inflammatory burdens beyond the throat, offering meaningful benefits for autoimmune and allergic diseases alike.

Conclusion

The last five years of research provide mounting evidence that the tonsils play a pivotal role in the pathogenesis of IgA Nephropathy. They appear not only to act as an upstream source of galactose-deficient IgA1 and immune complex formation but also as a potential target for therapeutic intervention. Tonsillectomy, particularly when performed early, offers a focused and often effective treatment with relatively low long-term side effects.

In contrast, steroid pulse therapy—while effective in many cases—carries a high burden of side effects and should be reserved for cases that do not respond sufficiently to tonsil removal. This evolving strategy honors the balance between scientific evidence and patient experience. It supports the notion that the road to recovery from IgAN often begins with removing the spark—before smothering the fire.

References

1. Nakayama T, Kaneko H, Suzuki Y, et al. Chronic Tonsillitis and IgA Nephropathy: Findings From a Nationwide Japanese Cohort Study. Am J Kidney Dis. 2024. Link
2. Hirano K, Matsuzaki K, Yasuda T, et al. Association Between Tonsillectomy and Outcomes in Patients With Immunoglobulin A Nephropathy. JAMA Netw Open. 2019;2(5):e194772. Link
3. Li Y, Tang Y, Lin T, Song T. Efficacy and Indications of Tonsillectomy in Patients With IgA Nephropathy: A Retrospective Study. PeerJ. 2022;10:e14481. Link
4. Wang J, Zhang M, Tang Z, et al. Histopathological Insights into the Tonsil-Kidney Axis in IgA Nephropathy. Int J Mol Sci. 2024;25(10):5298. Link
5. Hayashi H, Miura M, Nishimura K, et al. Tonsillectomy Improved Therapeutic Response in Anti-SRP Myopathy With IgA Nephropathy: A Case Report. Front Immunol. 2020;11:595480. Link
6. Bhattacharjee R, et al. Adenotonsillectomy in Children With Asthma: A Population-Based Study. PLoS Med. 2014;11(11):e1001753. Link