Peripheral immune cell and circulating cytokine alterations associated with hematologic involvement in primary Sjögren’s syndrome

To characterize peripheral immune alterations associated with hemat-ologic involvement (HI) in patients with primary Sjögren’s syndrome (pSS) andto assess the potential influence of leukopenia on differences in peripheral immune-cell counts. A total of 145 patients with pSS were included and classified according to the presence or absence of HI. Clinical and laboratory characteristics, peripheral lymphocyte subsets, immunoglobulins, and circulating cytokines were compared between patients with and without HI. A sensitivity analysis excluding patients with leukopenia was performed to assess its potential influence on immune-cell alterations. Univariable and multivariable logistic regression analyses were used to identify factors associated with HI. Spearman correlation analysis with hierarchical clustering was performed to characterize the correlation structure among peripheral immune parameters. Among the 145 patients, 47 had HI and 98 did not. Compared with the non-HI group, patients in the HI group exhibited higher erythrocyte sedimentation rates (ESR) and serum IgG levels, along with lower absolute counts of multiple peripheral lymphocyte subsets. Furthermore, circulating levels of IL-2, IL-4, IL-10, IL-17, IFN-γ, and TNF-α were higher in the HI group. After excluding patients with leukopenia, 123 patients remained (25 in the HI group and 98 in the non-HI group). In this subgroup, differences in most absolute lymphocyte counts were attenuated; however, the absolute Th1-cell count remained significantly lower in the HI group than in the non-HI group [72.70 (41.61–151.37) vs. 135.87 (60.02–218.96) cells/µL, P = 0.032]. In contrast, between-group differences in multiple circulating cytokines remained evident in the sensitivity analysis. Multivariable logistic regression analysis showed that higher ESR and lower absolute Th1-cell counts were significantly associated with HI. Hierarchical clustering revealed two relatively distinct correlation patterns corresponding to lymphocyte- and cytokine-related components. Hematologic involvement in patients with pSS is associated with alterations in peripheral immune cells and circulating cytokines. After excluding patients with leukopenia, lower absolute Th1-cell counts and higher levels of multiple circulating cytokines remained evident, suggesting that these alterations may represent peripheral immune features associated with HI.