Sjögren's disease (SjD) is a heterogeneous autoimmune disorder characterized by variable symptom burden, systemic activity, and glandular involvement. Recent phenotype-based stratification has identified distinct clinical subgroups; however, their corresponding glandular immunopathological and imaging features remain insufficiently defined.

To characterize glandular immune composition and structural involvement across clinically defined SjD subgroups-B-cell active disease with low symptom burden (BALS), high systemic activity (HSA), and low systemic activity and high symptom burden(LSAHS) by integrating quantitative immunohistochemistry (IHC) with salivary gland ultrasonography (SGUS) and shear wave elastography (SWE).

A total of 120 patients with suspected primary SjD were classified into BALS, HSA, and LSAHS subgroups. Labial salivary gland biopsies(LSGB) underwent quantitative IHC analysis for CD3⁺ T cells, CD20⁺ B cells, and CD45⁺ leukocytes. SGUS was scored using the OMERACT semi-quantitative system, and SWE-derived shear wave velocity (SWV) was measured in the parotid, submandibular, and lacrimal glands. Group comparisons and Spearman correlation analyses were performed.

BALS patients exhibited more severe salivary gland involvement than the other clinical subgroups. A higher proportion of BALS patients showed focus score (FS) ≥3 on LSGB and parotid SGUS scores ≥2. Quantitative immunohistochemistry revealed significantly greater CD20⁺ B-cell infiltration in BALS patients compared with LSAHS patients. SWE demonstrated significantly increased parotid gland stiffness in the BALS subgroup. In the overall cohort, parotid stiffness correlated positively with CD3⁺ T-cell, CD20⁺ B-cell, and CD45⁺ leukocyte infiltration areas. Subgroup analyses further showed that parotid stiffness was associated with CD20⁺ B-cell infiltration in BALS, whereas correlations with CD3⁺ T cells and CD45⁺ leukocytes were observed only in the LSAHS subgroup.

Clinically defined SjD subtypes exhibit distinct glandular immunopathological profiles: the BALS phenotype is associated with B-cell infiltration and increased parotid stiffness, whereas the LSAHS phenotype shows T-cell–dominant inflammation. Integration of quantitative IHC with parotid SWE offers a non-invasive assessment modality for refined SjD patient stratification and individualized treatment response monitoring.