A Systemic Immune State Axis Distinguishes Psoriatic Arthritis from Psoriasis

Area of Science:

• Immunology
• Genomics
• Dermatology

Background:

• Psoriasis and psoriatic arthritis (PsA) are systemic immune-mediated diseases.
• Distinguishing features between cutaneous psoriasis and PsA's musculoskeletal involvement are unclear.

Purpose of the Study:

• To define a disease inflammatory response axis (DIR) and a contrast-resolved systemic state coordinate (CRS).
• To understand systemic immune state variations associated with PsA compared to psoriasis.

Main Methods:

• Analysis of four core public cross-sectional datasets: whole-blood methylation, PBMC single-cell RNA sequencing, skin RNA sequencing, and CD4+ T-cell methylation.
• Utilized two additional public skin cohorts for validation.
• Defined DIR and CRS to represent systemic immune state variations.

Main Results:

• Whole-blood methylation showed DIR separating healthy controls from psoriasis, while CRS separated psoriasis from PsA.
• PBMC single-cell analysis revealed CRS distinguishing PsA from psoriasis, with shifts localized to T-cell, monocyte, B-cell, and regulatory compartments.
• Skin RNA sequencing primarily reflected lesional inflammatory burden, with limited additional PsA-related separation.

Conclusions:

• PsA is distinguished from psoriasis by an additional systemic immune state axis (CRS).
• Skin inflammatory burden alone does not fully explain the distinction between psoriasis and PsA.