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Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis

Research output: Contribution to journalArticlepeer-review

BADBIR, BSTOP Study Groups

Original languageEnglish
Pages (from-to)1617-1628.e10
JournalJournal of Investigative Dermatology
Volume142
Issue number6
DOIs
Accepted/In press2022
PublishedJun 2022

Bibliographical note

Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 821511 (Biomarkers in Atopic Dermatitis and Psoriasis). The Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations. This research has been conducted using the UK Biobank Resource (approved project 15147). Support for the study was received from the Department of Health through the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and comprehensive Biomedical Research Centre awards to Guy's and St Thomas’ National Health Service Foundation Trust in partnership with King's College London and King's College Hospital National Health Service Foundation Trust (reference: BRC_1215_20006). This study presents independent research supported by NIHR BioResource Centre Maudsley; NIHR Maudsley Biomedical Research Centre at South London; and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King's College London (United Kingdom). The BioResource gratefully acknowledges capital equipment funding from the Maudsley Charity (grant reference 980) and Guy's and St Thomas's Charity (grant reference STR130505). British Association of Dermatologists Biologics and Immunomodulators Register is coordinated by the University of Manchester and funded by the British Association of Dermatologists. The British Association of Dermatologists receives income from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung Bioepis, Sandoz Hexal AG, and UCB Pharma for providing pharmacovigilance services. This income finances a separate contract between the British Association of Dermatologists and The University of Manchester, which coordinate the British Association of Dermatologists Biologics and Immunomodulators Register. We would like to thank the Psoriasis Association for ongoing support and funding since the inception of Biomarkers of Systemic Treatment Outcomes in Psoriasis (reference: RG2/10: RG2/10). The authors acknowledge the invaluable support of the NIHR through the clinical research networks and its contribution in facilitating recruitment to both Biomarkers of Systemic Treatment Outcomes in Psoriasis and the British Association of Dermatologists Biologics and Immunomodulators Register. CEMG is funded in part by the NIHR Manchester Biomedical Research Centre and is an NIHR Emeritus Senior Investigator. SKM is funded by a Medical Research Council Clinical Academic Research Partnership award (MR/T02383X/1). NJR is an NIHR Senior Investigator and receives support from the Newcastle NIHR Biomedical Research Centre and the Newcastle NIHR Medtech and In Vitro Diagnostic Co-operative. RBW is supported by the Manchester NIHR Biomedical Research Centre. ND is funded by Health Data Research UK (MR/S003126/1). Members of the BADBIR Study Group (excluding individually named authors of this work) are Ian Evans, Ruth Murphy, Tess McPherson, Elise Kleyn, Philip Laws, Gabrielle Becher, Anthony Bewley, Amir Rashid, Oras Alabas, Simon Morrison, Shehnaz Ahmed, Eleanor Pearson, Josh Richards, Teena Mackenzie, Brian Kirby, David Burden, Linda Lawson, Kathleen McElhone, Anthony Ormerod, and Caroline Owen, Members of the BSTOP Study Group (excluding individually named authors of this work) are Nadia Aldoori, Mahmud Ali, Alex Anstey, Fiona Antony, Charles Archer, Suzanna August, Periasamy Balasubramaniam, Kay Baxter, Anthony Bewley, Alexandra Bonsall, Victoria Brown, Katya Burova, Aamir Butt, Mel Caswell, Sandeep Cliff, Mihaela Costache, Sharmela Darne, Emily Davies, Claudia DeGiovanni, Trupti Desai, Bernadette DeSilva, Victoria Diba, Eva Domanne, Harvey Dymond, Caoimhe Fahy, Leila Ferguson, Maria-Angeliki Gkini, Alison Godwin, Fiona Hammonds, Sarah Johnson, Teresa Joseph, Manju Kalavala, Mohsen Khorshid, Liberta Labinoti, Nicole Lawson, Alison Layton, Tara Lees, Nick Levell, Helen Lewis, Calum Lyon, Sandy McBride, Sally McCormack, Kevin McKenna, Serap Mellor, Ruth Murphy, Paul Norris, Caroline Owen, Urvi Popli, Gay Perera, Nabil Ponnambath, Helen Ramsay, Aruni Ranasinghe, Saskia Reeken, Rebecca Rose, Rada Rotarescu, Ingrid Salvary, Kathy Sands, Tapati Sinha, Simina Stefanescu, Kavitha Sundararaj, Kathy Taghipour, Michelle Taylor, Michelle Thomson, Joanne Topliffe, Roberto Verdolini, Rachel Wachsmuth, Martin Wade, Shyamal Wahie, Sarah Walsh, Shernaz Walton, Louise Wilcox, and Andrew Wright, Conceptualization: MAS, JNB, ND, CHS; Data Curation: KD, MD, ND; Formal Analysis: KD; Funding Acquisition: MAS, JNB, ND, CHS; Investigation: KD, DB, RC, SHL, ND, CHS; Methodology: KD, ND; Project Administration: IAB, ND, CHS; Resources: DB, MD, CA, RC, CJC, JMRG, CEMG, SHL, RP, NJR, ARS, RBW, CHS; Supervision: MAS, JNB, ND, CHS; Writing - Original Draft Preparation: KD, RR, ND, CHS; Writing - Review and Editing: KD, RR, IAB, DB, MD, CA, FC, RC, CJC, PDM, JMRG, CEMG, SHL, SKM, RP, NJR, ARS, RBW, ZZNY, MAS, JNB, ND, CHS, All decisions concerning analysis, interpretation, and publication are made independently of any industry contribution. Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 821511 (Biomarkers in Atopic Dermatitis and Psoriasis). The Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations . This research has been conducted using the UK Biobank Resource (approved project 15147). Support for the study was received from the Department of Health through the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and comprehensive Biomedical Research Centre awards to Guy’s and St Thomas’ National Health Service Foundation Trust in partnership with King’s College London and King’s College Hospital National Health Service Foundation Trust (reference: BRC_1215_20006). This study presents independent research supported by NIHR BioResource Centre Maudsley; NIHR Maudsley Biomedical Research Centre at South London; and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King's College London (United Kingdom). The BioResource gratefully acknowledges capital equipment funding from the Maudsley Charity (grant reference 980) and Guy’s and St Thomas’s Charity (grant reference STR130505). British Association of Dermatologists Biologics and Immunomodulators Register is coordinated by the University of Manchester and funded by the British Association of Dermatologists. The British Association of Dermatologists receives income from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung Bioepis, Sandoz Hexal AG, and UCB Pharma for providing pharmacovigilance services. This income finances a separate contract between the British Association of Dermatologists and The University of Manchester, which coordinate the British Association of Dermatologists Biologics and Immunomodulators Register. We would like to thank the Psoriasis Association for ongoing support and funding since the inception of Biomarkers of Systemic Treatment Outcomes in Psoriasis (reference: RG2/10: RG2/10). The authors acknowledge the invaluable support of the NIHR through the clinical research networks and its contribution in facilitating recruitment to both Biomarkers of Systemic Treatment Outcomes in Psoriasis and the British Association of Dermatologists Biologics and Immunomodulators Register. CEMG is funded in part by the NIHR Manchester Biomedical Research Centre and is an NIHR Emeritus Senior Investigator. SKM is funded by a Medical Research Council Clinical Academic Research Partnership award (MR/T02383X/1). NJR is an NIHR Senior Investigator and receives support from the Newcastle NIHR Biomedical Research Centre and the Newcastle NIHR Medtech and In Vitro Diagnostic Co-operative. RBW is supported by the Manchester NIHR Biomedical Research Centre. ND is funded by Health Data Research UK (MR/S003126/1). Publisher Copyright: © 2021 The Authors

King's Authors

Abstract

The identification of robust endotypes—disease subgroups of clinical relevance—is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom–based cross-sectional datasets—an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)—we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02–positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02–positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P = 2.7 × 10–14, UK Biobank: P = 1.0 × 10–8). We also show HLA-C∗06:02–negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02 = 0.73, P = 7.4 × 10–4; nail involvement, OR = 0.70, P = 2.4 × 10–6); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P = 8.4 × 10–4; UK Biobank: waist circumference difference of 1.4 cm, P = 1.5 × 10–4), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.

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