Risankizumab differentially modulates circulating T-cell populations in psoriasis according to autoreactivity status

Area of Science:

• Immunology
• Dermatology
• Pharmacology

Background:

• Psoriasis is linked to autoreactivity against LL37 and ADAMTSL5.
• Double autoreactivity to LL37 and ADAMTSL5 may predict reduced response to risankizumab.
• The impact of risankizumab on T-cell populations in autoreactive psoriasis patients is not well understood.

Purpose of the Study:

• To investigate how risankizumab affects circulating inflammatory T-cell populations in psoriasis patients.
• To specifically examine T-cell modulation in psoriatic patients with single or double autoreactivity to LL37 and ADAMTSL5.

Main Methods:

• Assessed LL37- and ADAMTSL5-reactive T-cells in 142 psoriasis patients (87 autoreactive at baseline).
• Administered risankizumab for 52 weeks, analyzing T-cell populations at various time points.
• Correlated T-cell frequencies with Psoriasis Area and Severity Index (PASI) scores.

Main Results:

• Risankizumab decreased inflammatory T-cells (Ki67+CD4+, Ki67+CD8+, CD8+IL-17+, CD8+IL-22+) correlating with PASI reduction.
• CD8+IL-17+ T-cell reduction occurred in single autoreactive groups but not double autoreactive.
• Treg frequency increased and IL-17+CD4+/Treg ratio decreased, except in double autoreactive subjects.
• MAIT cell subpopulations (CD8+MAIT IL-17+, CD3+MAIT IL-22+) decreased with IL-23 inhibition.

Conclusions:

• Risankizumab effectively reduces circulating inflammatory T-cells in single LL37- or ADAMTSL5-reactive psoriasis patients.
• Treg plasticity is modulated by risankizumab in single autoreactive individuals.
• Double autoreactivity to LL37 and ADAMTSL5 limits risankizumab's T-cell modulation effects.