HLA-B27 Status in Rheumatic Diseases: Clinical and Immunological Differences Between Positive and Negative Patients—A Comparative Study

<b>Background/Objectives</b>: Human leukocyte antigen B27 (HLA-B27) is a genetic marker strongly associated with various inflammatory rheumatic diseases, particularly those within the spondyloarthritis spectrum. Its presence influences disease onset, clinical severity, and therapeutic strategies. However, comparative data between HLA-B*27-positive and -negative patients, especially in Eastern European populations, remain limited. The study aimed to investigate the clinical, paraclinical, and psychosocial differences between HLA-B*27-positive and -negative individuals diagnosed with rheumatic diseases, in order to better understand the implications of HLA-B27 status on disease expression and patient quality of life. <b>Methods</b>: A cross-sectional, observational study was conducted between June 2023 and December 2024 at the Emergency Clinical Hospital for Children "Sf Ioan" in Galati, Romania, in collaboration with "Dunarea de Jos" University. Fifty adult patients with various rheumatic conditions were enrolled and stratified into HLA-B*27-positive (n = 22) and -negative (n = 28) groups. Data collection included clinical evaluations, laboratory biomarkers (CRP = C-reactive protein; ESR = erythrocyte sedimentation rate), and a structured quality-of-life questionnaire. Statistical analysis was performed using SPSS v27. <b>Results</b>: HLA-B*27-positive patients were significantly younger (mean age 46.00 vs. 55.07 years, <i>p</i> = 0.018) and had higher CRP levels (>1 mg/dL in 53.33% vs. 0%, <i>p</i> = 0.001). Ankylosing spondylitis was more prevalent in this group (22.73% vs. 3.57%, <i>p</i> = 0.039). Magnetic resonance imaging (MRI) was more frequently used (68.18% vs. 39.29%, <i>p</i> = 0.042), indicating greater suspicion of axial involvement. HLA-B27-positive patients also reported higher perceived stress (mean score 2.41 vs. 1.21, <i>p</i> < 0.001). <b>Conclusions</b>: HLA-B*27 positivity is associated with earlier disease onset, increased systemic inflammation, greater axial involvement, and higher psychological stress. These findings emphasise the need for personalised, multidisciplinary care that integrates both medical and psychological support for HLA-B*27-positive patients.