HLA Genotype is Associated with Patient Reported Outcomes and Adverse Reactions to Metal Debris in Patients with Cobalt-Chrome Knee Arthroplasties
- 1ExplantLab
Abstract
PurposeTo determine whether a cobalt-chrome genetic reactivity (CoGR) score - originally developed to identify patients at greater risk of developing adverse reaction to metal-on-metal hips - is associated with poorer patient-reported outcomes after knee arthroplasty (KA).
MethodsIn a prospective multicentre study, patients at a minimum two years post all cobalt-chrome KA were invited to research clinics. Participants provided samples for blood metal ion measurements and DNA sequencing and completed Forgotten Joint Scores (FJS). Component alignment was assessed on AP and lateral plain radiographs.
The association between CoGR and FJS was assessed using regression adjusted for time since surgery, age, gender, BMI and tested for modification by blood cobalt. In a case-control analysis, CoGR scores of revised patients with histologically confirmed adverse reactions to metal debris (and specifically aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL)) were compared with controls (revised patients with no signs of ARMD and unrevised patients with FJS of 75 or more) using Firth logistic regression.
Results376 patients were included: 312 unrevised patients and 64 patients who underwent revision. Each one-unit increase in CoGR score was associated with a 9.8 point lower FJS (95% confidence interval (CI) 4.2 to 15.4 points; p < 0.001). This increased to a 17.5 (9.4 to 25.5) point reduction per CoGR score unit in patients with blood cobalt above the median level. Comparing 28 ARMD cases (12 with ALVAL) with 177 controls, each one-unit CoGR increase was associated with odds ratios of 1.90 (CI 1.34 to 2.75) for ARMD and 3.05 (CI 1.89 to 5.34) for ALVAL.
ConclusionsA higher CoGR score was associated with worse patient-reported outcome and higher odds of histologically confirmed adverse reaction to metal debris at revision. Adverse immune responses may be a more significant factor in unexplained pain after KA than is generally recognised.
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BibTeX
@misc{langton2026genotype,
title = {{HLA Genotype is Associated with Patient Reported Outcomes and Adverse Reactions to Metal Debris in Patients with Cobalt-Chrome Knee Arthroplasties}},
author = {D. Langton and R. Bhalekar and Y. Borikar and S. Wells and N. Clement and D. Deehan and D. Guest and C. Harrington and S. Jameson and G. Leitch and R. McManus and M. Pabbruwe and J. Phillips and S. Rushton and A. Porteous and A. Santini and S. Tross and R. Sidaginamale},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.26365276},
url = {https://www.medrxiv.org/content/10.64898/2026.10.12.26365276v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - HLA Genotype is Associated with Patient Reported Outcomes and Adverse Reactions to Metal Debris in Patients with Cobalt-Chrome Knee Arthroplasties
AU - D. Langton
AU - R. Bhalekar
AU - Y. Borikar
AU - S. Wells
AU - N. Clement
AU - D. Deehan
AU - D. Guest
AU - C. Harrington
AU - S. Jameson
AU - G. Leitch
AU - R. McManus
AU - M. Pabbruwe
AU - J. Phillips
AU - S. Rushton
AU - A. Porteous
AU - A. Santini
AU - S. Tross
AU - R. Sidaginamale
PY - 2026
DA - 2026/10/12
PB - medRxiv
DO - 10.64898/2026.10.12.26365276
UR - https://www.medrxiv.org/content/10.64898/2026.10.12.26365276v1
AB - PurposeTo determine whether a cobalt-chrome genetic reactivity (CoGR) score - originally developed to identify patients at greater risk of developing adverse reaction to metal-on-metal hips - is associated with poorer patient-reported outcomes after knee arthroplasty (KA). MethodsIn a prospective multicentre study, patients at a minimum two years post all cobalt-chrome KA were invited to research clinics. Participants provided samples for blood metal ion measurements and DNA sequencing and completed Forgotten Joint Scores (FJS). Component alignment was assessed on AP and lateral plain radiographs. The association between CoGR and FJS was assessed using regression adjusted for time since surgery, age, gender, BMI and tested for modification by blood cobalt. In a case-control analysis, CoGR scores of revised patients with histologically confirmed adverse reactions to metal debris (and specifically aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL)) were compared with controls (revised patients with no signs of ARMD and unrevised patients with FJS of 75 or more) using Firth logistic regression. Results376 patients were included: 312 unrevised patients and 64 patients who underwent revision. Each one-unit increase in CoGR score was associated with a 9.8 point lower FJS (95% confidence interval (CI) 4.2 to 15.4 points; p < 0.001). This increased to a 17.5 (9.4 to 25.5) point reduction per CoGR score unit in patients with blood cobalt above the median level. Comparing 28 ARMD cases (12 with ALVAL) with 177 controls, each one-unit CoGR increase was associated with odds ratios of 1.90 (CI 1.34 to 2.75) for ARMD and 3.05 (CI 1.89 to 5.34) for ALVAL. ConclusionsA higher CoGR score was associated with worse patient-reported outcome and higher odds of histologically confirmed adverse reaction to metal debris at revision. Adverse immune responses may be a more significant factor in unexplained pain after KA than is generally recognised.
ER -