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Cited by 23Psoriasis: Treatment and PathogenesisDermatology and Skin DiseasesGenetic Associations and Epidemiology

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Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics

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Al-Janabi, Ali, Eyre, Steve, Foulkes, Amy C., Khan, Adnan R., Dand, Nick, Burova, Ekaterina, DeSilva, Bernadette, Makrygeorgou, Areti, Davies, Emily, Smith, Catherine H., Griffiths, Christopher E.M., Morris, Andrew P., Warren, Richard B.·2023·Journal of Investigative Dermatology
DOI 10.1016/j.jid.2023.01.021
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Abstract

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis is unknown. To identify risk variants, we conducted a GWAS of 3,212 patients with psoriasis, of whom 88 developed paradoxical eczema. Two lead SNPs reached genome-wide significance ( P ≤ 5 × 10 −8 ) for association with paradoxical eczema: rs192705221 (near UNC5B , P = 9.52 × 10 −10 ) and rs72925168 (within SLC1A2, P = 1.66 × 10 −9 ). Genome-wide significant SNPs from published GWAS were used to generate polygenic risk scores (PRSs) for atopic eczema, general atopic disease, or a combination, which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve. All three atopy polygenic risk scores were associated with paradoxical eczema ( P < 0.05); polygenic risk score for a combination of atopic eczema and general atopic disease had the strongest association (OR = 1.83, 95% CI = 1.17−2.84, P = 0.0078). Including atopic polygenic risk scores in the multivariable model, which included age, sex, atopic background, and psoriatic arthritis history, increased the area under the curve from 0.671 to 0.681−0.686. Atopic genetic burden is associated with paradoxical eczema occurring in biologic-treated patients with psoriasis, indicating shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis.

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  • Paradoxical eczema in patients with psoriasis using immunobiologicals was associated with variants that can influence the expression of transcripts or the amino acid sequence in the IL-12 pathway, but not in the IL4/13 and IL17/23 pathways.

    “Also, paradoxical eczema in patients with psoriasis using immunobiologicals was associated with variants that can influence the expression of transcripts or the amino acid sequence in the IL-12 pathway, but not in the IL4/13 and IL17/23 pathways.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [40]

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Research works printed but not linked: 40

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Metadata

Authors
Al-Janabi, A., Eyre, S., Foulkes, A. C., Khan, A. R., Dand, N., Burova, E., DeSilva, B., Makrygeorgou, A., Davies, E., Smith, C. H., Griffiths, C. E. M., Morris, A. P., & Warren, R. B.
Affiliations
  • Salford Royal NHS Foundation Trust (GB)
  • UCB Pharma (United Kingdom) (GB)
  • King's College London (GB)
  • Bedford Hospital NHS Trust (GB)
  • Luton and Dunstable University Hospital NHS Foundation Trust (GB)
  • Gloucestershire Royal Hospital (GB)
  • University of Manchester (GB)
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2023-08
Volume
143
Issue
8
Pages
1470-1478.e1
ISSN
0022-202X (ISSN-L)
DOI
10.1016/j.jid.2023.01.021
OpenAlex
W4320921499
Cited by
23
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 7
FWCI
2.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • King&apos;s College London
  • University of Manchester
  • Medical Research Council (MR/L011808/1)
  • Psoriasis Association
  • NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
  • NIHR Maudsley Biomedical Research Centre
  • UCB
  • Department of Health and Social Care
  • King’s College London
  • British Association of Dermatologists (RG2/10)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
psoriasis, biologic therapy, atopic dermatitis, atopic diseases, UNC5B, GLT-1, genetic risk factors, treatment outcome prediction, psoriatic arthritis
MeSH terms
Netrin Receptors, Biological Products, Dermatitis, Atopic, Eczema, Humans, Psoriasis, Risk Factors

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