Olink inflammatory biomarkers transform dermatological disease research
Dermatological diseases such as atopic dermatitis (AD), psoriasis and Hidradenitis Suppurativa (HS) are relatively common inflammatory disorders. In addition to causing discomfort and distress to patients, they can also be associated with serious comorbidities such as cardiovascular problems. Molecular profiling of disease lesions by techniques such as RNAseq is providing better insights into disease biology and potential therapeutic approaches, but this frequently requires biopsy sampling associated with patient discomfort and increased infection risk.
Recent studies, however, suggest that in some cases, disease site biology as measured by gene expression can be mirrored systemically at the protein level as blood biomarkers. This offers a minimally invasive method to study the inflammatory proteins involved in disease pathophysiology and treatment responses, as well as the potential to identify new diagnostic, prognostic, and predictive risk markers.
Olink® PEA – One scalable platform
The Proximity Extension Assay uses antibody pairs labeled with unique oligonucleotides to identify protein biomarkers with very high specificity, while qPCR or NGS ensures outstanding sensitivity on established technologies.
Learn more about Olink® PEA
Resources
Webinar
Getting under the skin of dermatological diseases using protein biomarkers
Leading experts, Dr. Emma Guttman and Dr. James Krueger, talk about the challenges of research into dermatological diseases and how proteomics is helping to move this field forward.
Watch the webinar
References
Inflammatory protein responses to anti-IL17RA therapy in hidradentis suppurativa
Navrazhina K, Frew JW, Grand D, et al. IL-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum. (2022) British Journal of Dermatology, DOI: 10.1111/bjd.21060.
“This research identifies lipocalin-2 in skin and IL-17A in serum as potential predictive biomarkers for treatment response. This may be useful in guiding physicians in choosing the appropriate therapy for patients with moderate-to-severe HS.”
This longitudinal study examined a small subset of patients enrolled in a trial for the anti-IL17RA drug brodalumab, using RNAseq and immunohistochemistry to look at local effects (lesional and perilesional skin), and proteomics using the Olink platform to look at systemic responses in serum. Protein data identified circulating IL-17A as a good baseline predictor of drug response and showed that some cytokines such as IL8 and TNF that were readily detectable at baseline were significantly reduced after 12 weeks of drug treatment.
Proteomic monitoring of drug responses in atopic dermatitis from tape-strip samples
He H, Olesen C, Pavel A, et al. Tape-Strip Proteomic Profiling of Atopic Dermatitis on Dupilumab Identifies Minimally Invasive Biomarkers (2021) Frontiers in Immunology, DOI: 10.3389/fimmu.2020.01768.
“These data emphasize the potential utility of tape-strip proteomic profiling for tracking biomarkers of therapeutic response in real-life settings as well as clinical trials and longitudinal studies of AD and beyond.”
In this exploratory study, the authors sought to characterize the proteomic signature of tape-strips from atopic dermatitis (AD) patients before and after treatment with the drug dupilumab. Analysis of samples from lesional and non-lesional skin using Olink panels showed that levels of >130 markers changed after drug treatment, with significant decreases in proteins associated with general inflammation, Th2 & Th17/Th22 responses, and innate immunity. These results demonstrate the feasibility of minimally invasive tape-strips for proteomic monitoring of therapeutic responses in AD patients.
Investigating drug mode of action in atopic dermatitis with proteomics
Bissonnette R, Maai C, Forman S, Bhatia N, Lee M, Fowler J, Tyring S, Pariser D, Sofen H, Dhawan S, Zook M, Zammit D, Usansky H, Denis L, Rao N, Song T, Pavel A and Guttman-Yassky E. (2019). British Journal of Dermatology, Doi: 10.1111/bjd.17932.
“Based on serum biomarker analyses, our study showed that ASN002 provided greater and more significant modulation of many key AD circulatory biomarkers compared with placebo, particularly at high dosages.”
The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study. In a clinical trial of dual kinase inhibitor therapy for atopic dermatitis, samples were taken longitudinally over the course of treatment and protein levels compared to those from placebo subjects. Drug treatment resulted in a significant reduction in serum levels of individual markers of general inflammation, T-cell/B-cell markers, T-cell activation, innate immunity, and T helper cell regulation. Pathway enrichment analysis indicated that cytokine–cytokine-receptor interaction, cytokine, Th1–Th2, inflammatory, chemokine-receptor binding, chemokine signaling, JAK-STAT signaling and IL-23 signaling were the primary pathways affected.