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

Abstract

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). 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. 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. 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.