Distinct immunological features characterize early-onset primary Sjögren's disease

Area of Science:

• Immunology
• Rheumatology
• Clinical Medicine

Background:

• Primary Sjögren's Disease (pSjD) has distinct phenotypes.
• Early-onset pSjD is associated with a poorer prognosis.
• Understanding immunophenotypic differences is crucial for targeted treatment.

Purpose of the Study:

• To compare the immunophenotypes of early- and late-onset pSjD.
• To identify distinct immunological features differentiating early-onset pSjD.
• To define a potential 'immune endotype' for early-onset pSjD.

Main Methods:

• Retrospective study of 204 newly diagnosed, untreated pSjD patients.
• Patients categorized by age at diagnosis (≤35 years for early-onset).
• Analysis of clinical features, peripheral lymphocyte profiles, CD4+ T cell subsets, cytokine levels, and statistical modeling (random forest, LASSO, logistic regression).

Main Results:

• Early-onset pSjD patients (n=43) showed significantly lower CD4+ T cell and NK cell counts compared to late-onset patients (n=161).
• The early-onset group had higher Th17/Treg cell ratios and lower Treg cell counts.
• Independent predictors for early-onset pSjD included NK cell counts, CD4+ T cell percentage, and Th17/Treg cell ratios.

Conclusions:

• Early-onset pSjD exhibits a distinct peripheral immunological profile.
• An 'immunological triad' (NK cells, CD4+ T cells, Th17/Treg ratio) may define an 'immune endotype' for early-onset pSjD.
• These findings offer insights for targeted monitoring and therapies in early-onset pSjD.