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Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty
  1. W John Armitage1,
  2. Helen L Winton1,
  3. Mark N A Jones2,
  4. Lewis Downward2,
  5. Julie M Crewe1,
  6. Chris A Rogers3,
  7. Derek M Tole4,
  8. Andrew D Dick1
  1. 1Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
  2. 2NHS Blood and Transplant, Bristol, United Kingdom
  3. 3Bristol Trials Centre, Bristol Medical School, University of Bristol, Bristol, United Kingdom
  4. 4Bristol Eye Hospital, Bristol, UK
  1. Correspondence to Professor W John Armitage, Translational Health Sciences, University of Bristol, Bristol Eye Hospital, Bristol BS1 2LX, UK; w.j.armitage{at}bristol.ac.uk

Abstract

Purpose A randomised trial to test the hypothesis that human leucocyte antigen (HLA) class II matching reduces the risk of allograft rejection in high-risk penetrating keratoplasty (PK).

Methods All transplants were matched for HLA class I antigens (≤2 mismatches at the A and B loci) and corneas were allocated to patients by cohort minimisation to achieve 0, 1 or 2 HLA class II antigen mismatches. The corneal transplants (n=1133) were followed for 5 years. The primary outcome measure was time to first rejection episode.

Results Cox regression analysis found no influence of HLA class II mismatching on risk of immunological rejection (HR 1.13; 95% CI 0.79 to 1.63; p=0.51). The risk of rejection in recipients older than 60 years was halved compared with recipients ≤40 years (HR 0.51; 95% CI 0.36 to 0.73; p=0.0003). Rejection was also more likely where cataract surgery had been performed after PK (HR 3.68; 95% CI 1.95 to 6.93; p<0.0001). In univariate analyses, preoperative factors including chronic glaucoma (p=0.02), vascularisation (p=0.01), inflammation (p=0.03), ocular surface disease (p=0.0007) and regrafts (p<0.001) all increased the risk of rejection. In the Cox model, however, none of these factors was individually significant but rejection was more likely where≥2 preoperative risk factors were present (HR 2.11; 95% CI 1.26 to 3.47; p<0.003).

Conclusions HLA class II matching, against a background of HLA class I matching, did not reduce the risk of allograft rejection. Younger recipient age, the presence of ≥2 preoperative risk factors and cataract surgery after PK all markedly increased the risk of allograft rejection.

Trial registration number ISRCTN25094892.

  • corneal transplantation
  • allograft rejection
  • immunological rejection
  • HLA matching
  • HLA class II

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Footnotes

  • Contributorship statement WJA, principal investigator with overall responsibility for the study, study design, data analysis and interpretation, drafting and revising paper; HLW, study coordinator, liaising with participating surgeons, contributed to drafting and review of paper; MNAJ, statistical analysis and data interpretation, contributed to drafting and review of paper; LD, statistical analysis and data interpretation, contributed to drafting and review of paper; JMC, study coordinator, liaising with participating surgeons, contributed to drafting and review of paper; CAR, statistical advice on study design, analysis and data interpretation, contributed to drafting and review of paper; DMT, corneal transplant surgeon, advised on clinical aspects of the study, recruited patients to the study, contributed to the drafting and review of the paper; ADD, consultant ophthalmologist and specialist in ocular immunology, advised on clinical and immunological aspects of the study and data interpretation, contributed to drafting and review of paper.

  • Funding The study was funded principally by the National Eye Research Centre (grant no. SCIAD036) with start-up funding from the NHS Executive South & West Research and Development Directorate (grant no. R/14/09/06).

  • Competing interests ADD, consultancies for Novartis, Ally and Alimera.

  • Patient consent for publication Not required.

  • Ethics approval National Institute for Health Research (NIHR) Clinical Research Network: UKCRN ID 9871. South West Research Ethics Committee favourable opinion: MREC/97/6/8. National Research Ethics Service: IRAS Project ID 11351.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. All the data used in the study are held by NHS Blood and Transplant in the UK Transplant Registry. The registry contains patient identifiable information and is therefore not directly publicly available.

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