Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics
Journal of Allergy and Clinical Immunology, 2023
Al-Janabi A., Martin P., Khan A., Foulkes A., Smith C., Griffiths C., Morris A., Eyre S., Warren R., Ahmed S., Alabas O., Barker J., Becher G., Bewley A., Evans I., Hampton P., Kirby B., Kleyn E., Laws P., Lawson L., Mackenzie T., McElhone K., McPherson T., Morrison S., Owen C., Pearson E., Rashid A., Reynolds N., Strangfeld A., Walton S., Yiu Z., Gupta G., Strangfeld (chair) A., Weller R., Zietemann V., Aldoori N., Ali M., Al-Rusan A., Angit C., Anstey A., Antony F., Archer C., August S., Balasubramaniam P., Baudry D., Baxter K., Bewley A., Bonsall A., Brown S., Brown V., Burden D., Burova E., Butt A., Caswell M., Chapman A., Cliff S., Costache M., Darne S., DeGiovanni C., Desai T., Diba V., Domanne E., Duckworth M., Dymond H., Fahy C., Farwer S., Ferguson L., Gkini M., Godwin A., Goulding J., Hammonds F., Haque S., Higgins C., Hood S., Joseph T., Johnson S., Kalavala M., Khorshid M., Labinoti L., Lamb R., Lawson N., Layton A., Lees T., Levell N., Lewis H., Lovell C., Lyon C., McAteer H., McBride S., McCormack S., McKenna K., Mellor S., Meredith F., Murphy R., Norris P., Owen C., Parslew R., Perera G., Ponnambath N., Popli U., Powell J., Ramesh R., Ramsay H., Ranasinghe A., Reeken S., Reynolds N., Rose R., Rotarescu R., Salvary I., Sands K., Sinha T., Schofield J., Shipman A., Siebert S., Stefanescu S., Sundararaj K., Taghipour K., Taylor M., Thomson M., Topliffe J., Verdolini R., Wachsmuth R., Wade M., Wahie S., Walsh S., Walton S., Wilcox L., Williamson D., Wright A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Dermatological Diseases | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Background
Few studies have explored the immunology and genetic risk of paradoxical eczema occurring as an adverse event of biologic therapy in patients with psoriasis.
Objectives
To describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore if this is genetically mediated.
Methods
We used the Olink Target 96 Inflammation panel on 256 serum samples from 71 psoriasis patients with paradoxical eczema, and 75 psoriasis controls to identify differentially expressed proteins and enriched gene sets. Case samples from one or more timepoints (T1 pre-biologic, T2 post-biologic, and T3 post-paradoxical eczema) were matched 1:1 with control samples. Genes contributing to enriched gene sets were selected, and functional single nucleotide polymorphisms (SNPs) used to create polygenic risk scores (PRS) in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls.
Results
STAM-binding protein expression was lower in cases at T1 than controls (log-fold change -0.44, adjusted P = 0.022); no other proteins reached statistical significance at equivalent timepoints. Eleven gene sets including cytokine and chemokine pathways were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, the majority are associated with the atopic dermatitis (AD) serum proteome. A PRS including 38 functional SNPs linked to enriched gene sets was associated with paradoxical eczema (adjusted P = 0.046).
Conclusion
The paradoxical eczema systemic inflammatory proteome trends towards AD at a gene-set level and is detectable before onset of the phenotype. This signature could be genetically determined.