Purpose: To investigate the clinical characteristics and prognostic significance of leukopenia and its components （lymphocytopenia and neutropenia）in patients with primary Sjögren's disease (pSjD). Particular attention was paid to the significance of lymphocyte phenotype in mortality prognosis among patients with pSjD. 

Patients and methods: This ambispective cohort study included patients from the Tao pSjD Multi-Omics Cohort (TSMC) treated at China-Japan Friendship Hospital between 2016 and 2022. Baseline clinical characteristics and associated factors were compared between patients with and without leukopenia and its components. During follow-up, risk factors for new-onset cytopenias and mortality were assessed.

Results: Among 1017 patients with pSjD, 269 (26.5%) had leukopenia, including 261 (25.7%) with lymphocytopenia and 96 (9.4%) with neutropenia at baseline. Patients with leukopenia exhibited enhanced humoral immune activation, hypocomplementemia and other cytopenias. Notably, lymphocytopenia was associated with a distinct inflammatory phenotype characterized by elevated CRP and ESR levels. During follow-up, low complement C3 levels were independently associated with an increased risk of new-onset leukopenia, particularly when C3 ≤0.61 g/L (HR 4.52, 95% CI 1.94–10.53). Importantly, baseline lymphocytopenia was independently associated with an increased risk of mortality. Patients with lymphocyte counts ≤0.39×10⁹/L had a more than sevenfold increased risk of death (HR 7.40, 95% CI 3.01–18.21). In patients with leukopenia or lymphocytopenia, elevated CRP may be associated with increased mortality risk.

Conclusion: Leukopenia is common in pSjD and reflects active humoral immune dysregulation. Among its components, lymphocytopenia defines a distinct high-risk inflammatory phenotype associated with significantly increased mortality. These findings highlight the importance of lymphocyte count as a clinically relevant marker for risk stratification and long-term management in pSjD.

Patients and methods: This ambispective cohort study included patients from the Tao pSjD Multi-Omics Cohort (TSMC) treated at China-Japan Friendship Hospital between 2016 and 2022. Baseline clinical characteristics and associated factors were compared between patients with and without leukopenia and its components. During follow-up, risk factors for new-onset cytopenias and mortality were assessed.

Results: Among 1017 patients with pSjD, 269 (26.5%) had leukopenia, including 261 (25.7%) with lymphocytopenia and 96 (9.4%) with neutropenia at baseline. Patients with leukopenia exhibited enhanced humoral immune activation, hypocomplementemia and other cytopenias. Notably, lymphocytopenia was associated with a distinct inflammatory phenotype characterized by elevated CRP and ESR levels. During follow-up, low complement C3 levels were independently associated with an increased risk of new-onset leukopenia, particularly when C3 ≤0.61 g/L (HR 4.52, 95% CI 1.94–10.53). Importantly, baseline lymphocytopenia was independently associated with an increased risk of mortality. Patients with lymphocyte counts ≤0.39×10⁹/L had a more than sevenfold increased risk of death (HR 7.40, 95% CI 3.01–18.21). In patients with leukopenia or lymphocytopenia, elevated CRP may be associated with increased mortality risk.

Conclusion: Leukopenia is common in pSjD and reflects active humoral immune dysregulation. Among its components, lymphocytopenia defines a distinct high-risk inflammatory phenotype associated with significantly increased mortality. These findings highlight the importance of lymphocyte count as a clinically relevant marker for risk stratification and long-term management in pSjD.