Novel clinical phenotype-based stratification identifies distinct immunopathological and ultrasonographic signatures in Sjögren's disease.

OBJECTIVES: To characterize glandular immune composition and structural involvement across clinically defined Sjögren's disease (SjD) subgroups-B-cell active disease with low symptom burden (BALS), high systemic activity (HSA), and low systemic activity with high symptom burden (LSAHS)-by integrating quantitative immunohistochemistry (IHC) with salivary gland ultrasonography (SGUS) and shear wave elastography (SWE). METHODS: A total of 120 SjD patients were classified into BALS, HSA, and LSAHS subgroups. Quantitative IHC was performed on labial salivary gland biopsy specimens for CD3⁺ T cells, CD20⁺ B cells, and CD45⁺ leukocytes. SGUS was scored using the OMERACT system, and SWE-derived shear wave velocity was measured in major salivary glands. Group comparisons and Spearman correlation analyses were performed. RESULTS: BALS patients showed more severe glandular involvement, with higher frequencies of focus score ≥3 and SGUS score ≥2. Quantitative IHC demonstrated increased CD20⁺ B-cell infiltration in BALS compared with LSAHS. SWE revealed elevated parotid stiffness in BALS. In the overall cohort, parotid stiffness correlated positively with CD3⁺, CD20⁺, and CD45⁺ infiltration. Subgroup analyses showed that parotid stiffness was associated with CD20⁺ B cells in BALS, whereas correlations with CD3⁺ T cells and CD45⁺ leukocytes were observed only in LSAHS. CONCLUSION: SjD clinical phenotypes exhibit distinct immunopathological and structural features.BALS is characterized by greater B-cell infiltration and more pronounced parotid involvement, whereas LSAHS shows a closer association between T-cell infiltration and glandular stiffness. Integrating immunopathological profiling with ultrasonographic elastography may improve phenotype-based assessment of glandular involvement.