Abstract
<title>Abstract</title> <p>Background Persistent pain after total knee arthroplasty (TKA) remains a challenging clinical problem with multifactorial etiology. Immunogenetic susceptibility has been proposed as a potential contributor to implant-related adverse reactions. Recent prospective biological evidence has reported associations between silicone implants and autoimmune markers, particularly involving major histocompatibility complex (MHC) genes such as human leukocyte antigen (HLA). These observations suggest that immunogenetic susceptibility could represent a contributing factor in patients with persistent pain of unknown origin after total knee arthroplasty (TKA). Purpose This study aimed to explore the prevalence of selected HLA alleles in patients with painful TKA of unclear origin, specifically HLA-DRB1*03 and HLA-B*08. Study Design and Level of evidence: Observational pilot study; Level IV evidence. Methods This observational pilot study included 50 patients with persistent unexplained pain following primary TKA, who fulfilled the predefined inclusion criteria of the study. All patients underwent standardized clinical evaluation to exclude common mechanical and infectious causes of postoperative pain. Demographic and clinical characteristics were recorded. HLA typing for HLA-B*08 and HLA-DRB1*03 was performed using DNA extracted from buccal swabs. Results The mean age of the cohort was 74.7 (SD 8.1). The mean body mass index was 31.3 kg/m² (SD 4.4). HLA-DRB1*03 was detected in 13 patients (26%), HLA-B*08 in 6 patients (12%), and combined positivity in 4 patients (8%). Overall, 15 patients (30%) tested positive for at least one of the analyzed HLA alleles. Conclusion In this pilot cohort of patients with persistent unexplained pain after TKA, HLA-B*08 and HLA-DRB1*03 were identified in a subset of patients. These descriptive findings provide preliminary data for the design of future controlled studies investigating potential immunogenetic contributions to persistent postoperative pain. Level of evidence Level IV, observational pilot study.</p>