This study aims to investigate the heterogeneous mechanisms of hematological impairment in primary Sjögren’s syndrome (pSS) by integrating clinical stratification of blood cell damage and antibody serotyping, to identify risk factors for patients with high-risk subtypes, and to further elucidate the underlying pathogenesis.

（1）A retrospective study was conducted involving 163 patients with pSS who were hospitalized in the Department of Rheumatology and Immunology at the Second Affiliated Hospital of Soochow University from January 2018 to December 2024. Demographic characteristics, clinical manifestations, comorbidities, laboratory parameters, and immunological indicators were extracted from their electronic medical record systems. Based on the presence or absence of baseline hematological impairment, patients were divided into an improvement group and a persistent impairment group. Multivariate logistic regression was used to screen for independent risk factors and to construct a predictive model. The model's discrimination, calibration, and clinical utility were evaluated using ROC curves, calibration curves, and decision curve analysis. Additionally, patients were followed up for one year to preliminarily assess the prognostic value of baseline risk factors.

（2）Based on the findings of the first part, further differences in clinical manifestations and serological indicators between the anti-SSB antibody-positive and anti-SSB antibody-negative groups among pSS patients were explored. Regarding the prognosis of anti-SSB antibody-positive patients, bioinformatics analysis was employed to screen and validate key genes associated with aggressive expression.

Part I: Predictive Value of Complement C3 Level and Anti-SSB Antibody for Cytopenia in pSS

（1）A total of 163 pSS patients were included in this study, among whom 70 (42.94%) presented with hematological impairment. The results showed that the hematological impairment group had significantly higher positivity rates of anti-SSA/Ro52 antibody and anti-SSB antibody, as well as significantly higher levels of globulin, IgG, and ESSDAI score, compared to the group without hematological impairment. In contrast, complement C3 and C4 levels were significantly lower in the hematological impairment group.

（2）In this study, the proportions of patients with anemia, leukopenia, thrombocytopenia, and multilineage impairment were 23.3% (38 cases), 24.5% (40 cases), 9.8% (16 cases), and 11.7% (19 cases), respectively. Patients with multilineage impairment had higher IgG level, disease activity score, and anti-SSB antibody positivity rate, as well as lower complement C3 level.

（3）Complement C3 level was identified as an independent protective factor for cytopenia, anemia, leukopenia, and multi-lineage cytopenia in pSS patients. Anti-SSB antibody was a risk factor for hematological involvement and anemia. The incidence of purpura and IgM level were risk factors for thrombocytopenia.

（4）The combination of complement C3 level and positive Anti-SSB antibody has diagnostic value for cytopenia.

（5）During the one-year follow-up of patients with hematological involvement, it was found that baseline complement C3 level in patients with persistent hematological involvement were significantly lower than those in the improved group (0.63 g/L vs. 0.77 g/L, P=0.002). Baseline complement C3 level demonstrated good predictive value for persistent hematological involvement.

Part II: Comparison of Clinical Characteristics and Screening and Validation of Key Genes Between Anti-SSB Antibody-Positive and Anti-SSB Antibody-Negative Patients

（1）Compared with anti-SSB antibody negative patients, anti-SSB antibody positive patients had significantly higher incidences of parotid gland enlargement and lymphadenopathy, as well as significantly higher ANA titer, erythrocyte sedimentation rate, IgG, IgA, and RF levels, and were associated with a higher disease activity score (6.0 vs 4.5, P=0.013). Furthermore, anti-SSB antibody positivity was associated with peripheral blood leukopenia, neutropenia, and anemia.

（2）During the one‑year follow‑up, the unplanned readmission rate (56.1% vs 28.6%, P = 0.003) and total hospital days (5.8 vs 2.7, P = 0.01) were significantly higher in the anti‑SSB‑positive group than in the anti‑SSB‑negative group.

（3）Bioinformatics analysis was performed on 236 anti-SSB antibody negative and 115 anti-SSB antibody positive pSS patients from the GSE140161 dataset. A total of 205 differentially expressed genes were identified, including 158 upregulated genes and 47 downregulated genes. Through protein-protein interaction (PPI) network analysis, five key genes, namely IFIT3, RSAD2, IFI44, IFIT2, and IFIT1, were screened out. Subsequent qRT-PCR validation demonstrated that the transcriptional levels of IFIT3, RSAD2, and IFIT2 were significantly higher in anti-SSB antibody positive patients than in the negative group.

（1）Low complement C3 level and positive anti-SSB antibody are risk factors for hematological impairment in patients with pSS.

（2）Decreased complement C3 level may be associated with the persistence of hematological impairment, and the readmission rate is significantly higher in patients with positive anti-SSB antibody.

（3）The aggressive phenotype associated with anti-SSB antibody-positive patients is pathologically closely related to the activation of the type I interferon pathway and is significantly correlated with elevated transcriptional levels of IFIT3, RSAD2, and IFIT2.