Establishing the Frequency of the HLA Class II Pseudotumour 'at Risk' Genotype: A Pilot Epidemiologic Analysis

Immune-mediated adverse local tissue reactions (ALTRs) to implanted metallic devices are an increasingly recognised orthopaedic concern. Recent research has identified a critical HLA genotype associated with increased risk of ALTR development around in situ arthroplasty implants. Carriage imparts a > 700% increased relative-risk of high-grade peri-prosthetic lesion development, associated with pain and joint dysfunction and likely contributing to an increased burden of complex revision surgery. Despite being first reported in 2017, the 'at risk' genotype has only subsequently been described in selected metal-on-metal and revision arthroplasty cohorts and no population-level prevalence data has been reported. This novel epidemiologic pilot investigation aimed to explore allele-variant carriage frequencies of the previously-described 'at risk' HLA genotype in an undifferentiated orthopaedic population to inform larger screening investigations.

One hundred consecutive patients were prospectively recruited. Targeted HLA class II genotyping was performed using a medium-resolution Luminex-based approach, and secondary screening was performed to identify the presence of four specific alleles previously-associated with immune-mediated reactions to implanted metal devices.

Our findings, in a non-differentiated orthopaedic cohort, suggest a carrier rate of the previously-defined 'at risk' allele of 38%, with 29% of those sampled carrying the defined 'at risk' genotype.

Our results show a higher-than-anticipated incidence of the 'at risk' gene and genotype. As genotype-associated ALTRs may contribute to patient dissatisfaction following primary joint replacements, the impact of this result may be greater than had previously been considered. While acknowledging the preliminary nature of these data, they may guide future screening applications of the genotyping analysis and will provide a foundation contribution-to-knowledge for future endeavours in diverse populations.