Anti-tumour necrosis factor-alpha response associated with combined CD226 and HLA-DRB1*0404 haplotype in rheumatoid arthritis.

D. S. Gibson, C. M. McGeough, S. Watterson, J. Blayney, G. D. Wright, A. Pendleton, P. Gardiner, D. Small, A. J. Eakin, T. Ahmed, H. A. Murray, M. J. Latten, M. A. Crockard, J. V. Lamont, S. D. Zhang, A. J. Bjourson

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Predicting response to anti-tumour necrosis factor alpha (anti-TNFα) drugs at baseline remains an elusive goal in rheumatoid arthritis (RA) management. The purpose of this study was to determine if baseline genetic variants of PTPRC, AFF3, myD228, CHUK, MTHFR1, MTHFR2, CD226 and a number of KIR and HLA alleles could predict response to anti-TNFα in rheumatoid arthritis patients.
Peripheral blood samples were collected from 238 RA patients treated with anti-TNFα drugs. Genotyping was performed using biochip array technology by Randox Laboratories Ltd. and sequence specific polymerase chain reaction. Linear regression analysis was performed to investigate the role of these genotypes in predicting response to treatment, as defined by European League Against Rheumatism (EULAR) response classification and absolute change in disease activity score (DAS28).
Of 238 RA patients analysed, 50.4% received adalimumab, 29.7% received etanercept, 14.8% received infliximab, 3.4% certoluzimab and 1.7% golimumab. The MTHFR1 variant rs1801133 was significantly associated with the EULAR response, p=0.044. Patients with the HLA-DRB1*0404 allele displayed a significantly larger reduction in DAS28 compared to non-carriers (mean -2.22, -1.67 respectively, p=0.033). CD226 rs763361 was the only SNP variant significantly associated with ∆DAS28 (p=0.029)
This study has investigated individual allele associations with reductions in DAS28 across a range of anti-TNFα treatments. A combined predictive model indicates that patients with the HLA-DRB1*0404 allele and without the CD226 rs763361 polymorphism exhibit the largest reduction in DAS28 after anti-TNFα treatment.
Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalClinical and Experimental Rheumatology
Issue number2
Early online date8 Jan 2021
Publication statusPublished (in print/issue) - 9 Apr 2021

Bibliographical note

Funding Information:
A. Bjourson and D. Gibson wish to ac knowledge the award of PhD fellow ships from the Department for Econo my and support from Northern Ireland Rheumatism Trust, both Northern Ireland, UK. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding Information:
Funding: this work was supported by a grant to A.J. Bjourson from Innovate UK and the NI Centre for Stratified Medicine has been funded under the EU Regional Development Fund EU Sustainable Competitiveness Programme for NI & the NI Public Health Agency. Competing interests: none declared.

Publisher Copyright:
© Copyright CliniCal and Experimental Rheumatology 2021.


  • Anti-TNF-α
  • Genotype
  • Polymorphism
  • Response prediction
  • Rheumatoid arthritis


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