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Integrated Proteogenomics and Single-Cell Transcriptomics Prioritize Putative Protective Plasma Proteins for
Yuzhe Cheng1,2, Jingyi Ma1, Jun Niu1
1Department of Dermatology, General Hospital of Northern Theatre Command, Shenyang, China.
Experimental Dermatology
|July 25, 2026
Summary
This study identifies three plasma proteins—TNFRSF6B, FCRL2, and APOD—that may offer protection against hidradenitis suppurativa (HS). TNFRSF6B shows the strongest genetic evidence, suggesting its potential as a therapeutic target for HS.
Area of Science:
- Genetics
- Proteomics
- Immunology
Background:
- Genetic susceptibility loci for hidradenitis suppurativa (HS) are often in non-coding regions, complicating target identification.
- Tissue-level transcriptomics struggle to differentiate causal factors from secondary inflammation in HS.
Purpose of the Study:
- To prioritize plasma proteins causally linked to HS risk using genetic prediction.
- To determine the cellular localization of these proteins within human skin.
Main Methods:
- Two-sample Mendelian randomization (MR) was employed using cis-protein quantitative trait loci (pQTL) instruments for 2923 plasma proteins.
- UK Biobank Pharma Proteomics Project data was analyzed against HS summary statistics from FinnGen R12.
- Bayesian colocalization and false-discovery rate (FDR) correction were applied to identify significant associations.
Main Results:
- Three protective protein candidates were identified: TNFRSF6B (OR=0.748), FCRL2 (OR=0.896), and APOD (OR=0.789).
- Single-cell transcriptomics localized FCRL2 to B cells and NK cells, and APOD to keratinocytes, macrophages, and dendritic cells.
- TNFRSF6B was not detected in skin, consistent with a circulating decoy receptor role.
Conclusions:
- TNFRSF6B, FCRL2, and APOD are prioritized as putative protective plasma proteins for HS.
- The integrated proteogenomic and single-cell approach provides valuable insights into HS pathogenesis.
- TNFRSF6B is highlighted as a robust candidate for future translational research in HS.