# Surgical removal of Waldeyer’s ring and long-term risk of Sjögren’s syndrome: a population-based cohort study investigating the mucosal immune link

**Authors:** Hua-Wei Chi, Chia-Hung Su, Yu-Hsun Wang, Chun-Hou Liao, Mingchih Chen, Jeng-Wen Chen, James Cheng-Chung Wei

PMC · DOI: 10.3389/fimmu.2026.1760386 · Frontiers in Immunology · 2026-02-05

## TL;DR

Removing tonsils and adenoids increases the long-term risk of developing Sjögren’s syndrome, especially in children and African Americans.

## Contribution

This study is the first to show a population-level link between tonsillectomy/adenoidectomy and increased Sjögren’s syndrome risk.

## Key findings

- Tonsillectomy/adenoidectomy is associated with a 52% higher risk of Sjögren’s syndrome.
- The risk is highest in individuals operated on before age 18 and in African American patients.
- Sensitivity analyses confirm the association is specific to Sjögren’s syndrome and not other conditions.

## Abstract

The palatine tonsils and adenoids are critical inductive sites for the mucosa-associated lymphoid tissue (MALT) system, educating B cells for salivary defense. While their removal is common, the long-term impact on mucosal autoimmunity remains unclear. We hypothesized that disrupting this lymphoid network increases susceptibility to Sjögren’s syndrome (SS).

Using the TriNetX US Collaborative Network (2006–2023), we conducted a retrospective cohort study matching 302,737 patients who underwent tonsillectomy/adenoidectomy with 302,737 non-surgical controls (propensity score-matched 1:1). Hazard ratios (HR) for incident SS were estimated using Cox proportional hazards models.

The surgical cohort exhibited a significantly elevated risk of SS (HR 1.52; 95% CI 1.23–1.87; p<0.001) compared to controls. This risk was most profound in individuals operated on before age 18 (HR 2.27) and in African American patients (HR 2.26). Sensitivity analyses using negative outcome controls (e.g., burns, injuries) confirmed the specificity of the association.

Tonsillectomy is independently associated with an increased risk of SS. These findings suggest that early-life removal of nasopharyngeal lymphoid tissue may disrupt the MALT axis, impairing oral tolerance and predisposing to salivary autoimmunity.

## Full-text entities

- **Genes:** CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, IRF5 (interferon regulatory factor 5) [NCBI Gene 3663] {aka SLEB10}, HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}, CCR10 (C-C motif chemokine receptor 10) [NCBI Gene 2826] {aka GPR2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}
- **Diseases:** malignant neoplasms (MESH:D009369), SS (MESH:D012859), spike (MESH:D031261), inflammation (MESH:D007249), abscess (MESH:D000038), injuries (MESH:D014947), C-HL (MESH:C538324), respiratory infections (MESH:D012141), adenoidal disorder (MESH:D003528), tonsillar (MESH:D014067), gout (MESH:D006073), obstructive airway disease (MESH:D000402), palmoplantar pustulosis (MESH:D011565), IgA nephropathy (MESH:D005922), frailty (MESH:D000073496), peritonsillar abscess (MESH:D000039), burns (MESH:D002056), Waldeyer's ring (MESH:D012303), autoimmune (MESH:D001327), fatigue (MESH:D005221), infection (MESH:D007239), fire (MESH:D000092422), rheumatoid arthritis (MESH:D001172), immunodeficiency (MESH:D007153), death (MESH:D003643), multiple sclerosis (MESH:D009103), keratoconjunctivitis sicca (MESH:D007638), immune dysregulation (OMIM:614878), lymphocytic sialadenitis (MESH:D012793), parotid swelling (MESH:D010309), acute tonsillitis (MESH:D014069), obstructive sleep-disordered breathing (MESH:D012891), dryness (MESH:D014987), autoimmune thyroiditis (MESH:D013967), obstructive sleep apnea (MESH:D020181), inflammatory bowel disease (MESH:D015212), kidney (MESH:D007674), allergic diseases (MESH:D004342)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916558/full.md

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Source: https://tomesphere.com/paper/PMC12916558