The John Charnley Award: The Impact of Human Leukocyte Antigen Genotype on Bacterial Infection Rates and Successful Eradication in Total Hip Arthroplasty

Background: Genetics play an important role in several medical domains; however, the influence of human leukocyte antigen (HLA) genotype on the development of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) remains unknown. The primary aim of this study was to determine if HLA genotype is associated with the development of bacterial PJI in THA. Secondarily, we evaluated the association between HLA genotype and PJI treatment success.

Methods: A retrospective, matched, case-control study was performed using prospectively collected data from a single institution. A total of 49 patients who underwent primary THA were included, with a mean follow-up of 8.5 years (range, 4.2 to 12.9). The 23 cases (PJI) and 26 controls (no PJI) were matched for age, sex, follow-up, body mass index, primary diagnosis, and comorbidities (P > .05). High-resolution genetic analysis targeting 11 separate HLA loci was performed in all patients using serum samples. The HLA gene frequencies and carriage rates were determined and compared between cohorts. A subgroup analysis of PJI treatment success (18) and failure (5) was performed. Statistical significance was set at P = .10 for genetic analysis and at 0.05 for all other analyses.

Results: There were 4 HLA alleles that were significantly associated with the development of PJI. The 3 at-risk alleles included HLA-C∗06:02 (odds ratio 5.25, 95% CI [confidence interval] 0.96 to 28.6, P = .064), HLA-DQA1∗04:01 (P = .096), and HLA-DQB1∗04:02 (P = .096). The single protective allele was HLA-C∗03:04 (odds ratio 0.12, 95% CI 0.01 to 1.10, P = .052). There were no specific HLA alleles that were associated with treatment success or failure.

Conclusions: This study suggests that there are at-risk and protective HLA alleles associated with the development of PJI in THA. To our knowledge, this is the first study to demonstrate an association between patient HLA genotype and the development of PJI. A larger study of the subject matter is necessary and warranted.