Background/Purpose: In primary Sjögren’s syndrome (pSS), the histologic focus score reflects immune infiltration but does not capture irreversible glandular damage. We evaluated a submandibular gland (SMG) gland ratio—defined as the proportion of preserved parenchyma in biopsy sections—as a marker of structural integrity, and assessed its associations with salivary function, serology, and imaging.

Methods: We analyzed 51 anti-SSA⁺ pSS patients who underwent SMG core needle biopsy (CNB); 46 had paired parotid gland (PG) CNB. The gland ratio was calculated as the area of preserved acini and ducts divided by total tissue area, including stroma, adipose, and fibrosis. Patients were stratified by SMG gland ratio tertiles. Salivary function was assessed by unstimulated whole salivary flow (UWSF) and Saxon test. Serologic markers included IgG, rheumatoid factor (RF), complement, and CK. Among 29 patients, SMG sialoscintigraphy was performed. In 36 patients, p16⁺ cells were quantified in striated ducts by immunohistochemistry.

Results: Lower SMG gland ratios were associated with impaired salivary function. UWSF increased from median 0.02 to 0.20 mL/min across tertiles (p< 0.001); Saxon test rose from 1.3 to 4.1 mL/2 min (p< 0.001). IgG (p=0.008) and RF (p< 0.001) decreased with greater gland preservation. Echography scores (OMERACT) also declined with increasing gland ratio (p=0.011). SMG gland ratio correlated with sialoscintigraphy uptake (ρ=0.55–0.61) and maximal secretion (ρ=0.63–0.65). PG gland ratio showed marginal association with Saxon (p=0.067) but not UWSF. In a subset (n=36), p16⁺ cells in striated ducts showed a bell-shaped association with gland ratio, peaking near 0.5, suggesting senescence may rise before overt tissue loss.

Conclusion: The SMG gland ratio stratifies salivary function, immune activity, and imaging findings in anti-SSA⁺ pSS, supporting its potential as a histologic anchor for structural damage staging. Preliminary findings further suggest senescence may peak in moderately preserved glands, highlighting its possible role in early irreversible injury.

Figure 1. Salivary function and serologic activity across tertiles of submandibular gland (SMG) gland ratio. (A–B) Saxon test and unstimulated whole salivary flow (UWSF) improved with increasing gland preservation. (C–D) Serum IgG and rheumatoid factor decreased across tertiles. SMG, submandibular gland; UWSF, unstimulated whole salivary flow.

Figure 2. p16⁺ cell percentage in striated ducts (STD) across submandibular gland (SMG) gland ratio tertiles in anti-SSA⁺ pSS (n = 36). (Left) Boxplot showing increased p16⁺ burden in mid- and high-tertile groups. (Right) Quadratic regression model reveals a bell-shaped association, peaking near gland ratio 0.5 (95% bootstrap CI shaded). No similar pattern was observed in anti-SSA⁻ patients (not shown).

Table 1. Clinical, serologic, and imaging features across submandibular gland (SMG) gland ratio tertiles. Gland ratio was defined as the preserved parenchymal area over total biopsy section. p-values based on Kruskal–Wallis test. UWSF, unstimulated whole salivary flow; ESSDAI, EULAR Sjögren’s syndrome disease activity index.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/submandibular-gland-ratio-stratifies-salivary-function-and-reveals-a-senescence-peak-in-anti-ssa-positive-sjogrens-syndrome/