Identification of protective and 'at risk' HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings

Gerard A Sheridan; Michael Hanlon; Adanna Welch-Phillips; Karen Spratt; Richard Hagan; John M O'Byrne; Patrick J Kenny; Andrew P Kurmis; Bassam A Masri; Donald S Garbuz; Conor J Hurson

doi:10.1302/2633-1462.43.BJO-2023-0003.R1

Identification of protective and 'at risk' HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings

Bone Jt Open. 2023 Mar 14;4(3):182-187. doi: 10.1302/2633-1462.43.BJO-2023-0003.R1.

Authors

Gerard A Sheridan^{1

2

3}, Michael Hanlon¹, Adanna Welch-Phillips¹, Karen Spratt¹, Richard Hagan⁴, John M O'Byrne^{1

2}, Patrick J Kenny¹, Andrew P Kurmis^{5

6}, Bassam A Masri³, Donald S Garbuz³, Conor J Hurson¹

Affiliations

¹ National Orthopaedic Hospital Cappagh, Dublin, Ireland.
² Royal College of Surgeons in Ireland, Dublin, Ireland.
³ University of British Columbia, Vancouver, Canada.
⁴ National Blood Centre, Irish Blood Transfusion Service, Dublin, Ireland.
⁵ College of Medicine & Public Health, Flinders University, Bedford Park, SA, Australia.
⁶ Discipline of Medical Specialties, University of Adelaide, Adelaide, SA, Australia.

PMID: 37051827
PMCID: PMC10032235
DOI: 10.1302/2633-1462.43.BJO-2023-0003.R1

Abstract

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. 'Controls' were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two 'at risk' alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.