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. 2026 Feb 5:17:1760386.
doi: 10.3389/fimmu.2026.1760386. eCollection 2026.

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

Hua-Wei Chi #  1   2 , Chia-Hung Su #  1 , Yu-Hsun Wang  3 , Chun-Hou Liao  4 , Mingchih Chen  5   6 , Jeng-Wen Chen  1   2   5 , James Cheng-Chung Wei  7   8   9
Affiliations

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

Hua-Wei Chi et al. Front Immunol. .

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Sjögren’s syndrome; TriNetX; adenoidectomy; autoimmune disease; immune tolerance; tonsillectomy.

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Conflict of interest statement

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) J-CW declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Study flow diagram illustrating patient identification and propensity score matching process. CRP, C reactive protein; ESR, erythrocyte sedimentation rate.
Figure 2
Figure 2
Kaplan–Meier curves showing cumulative incidence of Sjögren’s syndrome in surgical versus non-surgical cohorts.
Figure 3
Figure 3
Forest plot of subgroup-specific hazard ratios with 95% confidence intervals.
See this image and copyright information in PMC

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