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

doi:10.55563/clinexprheumatol/u1mi30

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

OBJECTIVES: 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-TNF-α in rheumatoid arthritis patients.

METHODS: 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).

RESULTS: 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 ΔDAS28 (p=0.029).

CONCLUSIONS: 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-TNF-α treatment.

Original language	English
Pages (from-to)	385-392
Number of pages	8
Journal	Clinical and Experimental Rheumatology
Volume	39
Issue number	2
DOIs	https://doi.org/10.55563/clinexprheumatol/u1mi30
Publication status	Published - 01 Mar 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.

Keywords

Anti-TNF-α
Genotype
Polymorphism
Response prediction
Rheumatoid arthritis

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology

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Cite this

Gibson, D. S., McGeough, C. M., Watterson, S., Blayney, J., Wright, G. D., Pendleton, A., Gardiner, P., Small, D., Eakin, A. J., Ahmed, T., Murray, H. A., Latten, M. J., Crockard, M. A., Lamont, J. V., Zhang, S. D., & Bjourson, A. J. (2021). Anti-tumour necrosis factor-alpha response associated with combined CD226 and HLA-DRB1*0404 haplotype in rheumatoid arthritis. Clinical and Experimental Rheumatology, 39(2), 385-392. https://doi.org/10.55563/clinexprheumatol/u1mi30

@article{78ef247691e24b87921d5f8778d6994a,

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

abstract = "OBJECTIVES: 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-TNF-α in rheumatoid arthritis patients.METHODS: 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).RESULTS: 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 ΔDAS28 (p=0.029).CONCLUSIONS: 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-TNF-α treatment.",

keywords = "Anti-TNF-α, Genotype, Polymorphism, Response prediction, Rheumatoid arthritis",

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

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: {\textcopyright} Copyright CliniCal and Experimental Rheumatology 2021.",

year = "2021",

month = mar,

day = "1",

doi = "10.55563/clinexprheumatol/u1mi30",

language = "English",

volume = "39",

pages = "385--392",

journal = "Clinical and Experimental Rheumatology",

issn = "0392-856X",

publisher = "Clinical and Experimental Rheumatology S.A.S.",

number = "2",

}

Gibson, DS, McGeough, CM, Watterson, S, Blayney, J, Wright, GD, Pendleton, A, Gardiner, P, Small, D, Eakin, AJ, Ahmed, T, Murray, HA, Latten, MJ, Crockard, MA, Lamont, JV, Zhang, SD & Bjourson, AJ 2021, 'Anti-tumour necrosis factor-alpha response associated with combined CD226 and HLA-DRB1*0404 haplotype in rheumatoid arthritis', Clinical and Experimental Rheumatology, vol. 39, no. 2, pp. 385-392. https://doi.org/10.55563/clinexprheumatol/u1mi30

TY - JOUR

T1 - Anti-tumour necrosis factor-alpha response associated with combined CD226 and HLA-DRB1*0404 haplotype in rheumatoid arthritis

AU - Gibson, D. S.

AU - McGeough, C. M.

AU - Watterson, S.

AU - Blayney, J.

AU - Wright, G. D.

AU - Pendleton, A.

AU - Gardiner, P.

AU - Small, D.

AU - Eakin, A. J.

AU - Ahmed, T.

AU - Murray, H. A.

AU - Latten, M. J.

AU - Crockard, M. A.

AU - Lamont, J. V.

AU - Zhang, S. D.

AU - Bjourson, A. J.

N1 - 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.

PY - 2021/3/1

Y1 - 2021/3/1

N2 - OBJECTIVES: 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-TNF-α in rheumatoid arthritis patients.METHODS: 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).RESULTS: 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 ΔDAS28 (p=0.029).CONCLUSIONS: 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-TNF-α treatment.

AB - OBJECTIVES: 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-TNF-α in rheumatoid arthritis patients.METHODS: 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).RESULTS: 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 ΔDAS28 (p=0.029).CONCLUSIONS: 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-TNF-α treatment.

KW - Anti-TNF-α

KW - Genotype

KW - Polymorphism

KW - Response prediction

KW - Rheumatoid arthritis

U2 - 10.55563/clinexprheumatol/u1mi30

DO - 10.55563/clinexprheumatol/u1mi30

M3 - Article

C2 - 33427622

AN - SCOPUS:85104275988

SN - 0392-856X

VL - 39

SP - 385

EP - 392

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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