Ustekinumab improves psoriasis-related gene expression in noninvolved psoriatic skin without inhibition of the antimicrobial response.
Baerveldt. E M EM; Onderdijk. A J AJ; Kurek. D D; Kant. M M; Florencia. E F EF; Ijpma. A S AS; van der Spek. P J PJ; Bastiaans. J J; Jansen. P A PA; van Kilsdonk. J W J JW; Laman. J D JD; Prens. E P EP
Key Findings
- Ustekinumab reduced NGF and increased GATA3 and IL‑22RA1 expression in non‑lesional skin, suggesting less skin reactivity
- Levels of antimicrobial peptides hBD‑2, S100A7 and LL‑37 stayed the same after treatment
- Eight of 11 patients achieved at least a 50% drop in PASI score after 4 weeks, with lower serum hBD‑2
Practical Outcomes
- For self‑experimenters, the data suggest that ustekinumab (a prescription biologic) does not suppress the skin’s natural antimicrobial peptide LL‑37, so immune defense isn’t compromised. However, the study offers no new dosing tips or direct ways to use LL‑37 for health benefits.
Summary
A single dose of the psoriasis drug ustekinumab lowered some skin genes linked to psoriasis but didn’t change the levels of the antimicrobial peptide LL‑37 or other skin defenses. Patients also showed clinical improvement and some shifts in blood inflammation proteins.
Abstract
Ustekinumab is a fully human anti-p40 monoclonal antibody which neutralizes interleukin (IL)-12 and IL-23, thereby interfering with T-helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation. To determine whether ustekinumab improves psoriasis-related gene expression and tape-strip responses in noninvolved skin. Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape-stripped. After 5 h, biopsies were taken from untouched and tape-stripped skin. The mRNA expression of psoriasis-related markers such as NGF, GATA3 and IL-22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations. Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL-22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation-related serum proteins GPNMB, MST1 and TRADD. The baseline and tape-strip-induced mRNA expression of the AMP human β-defensin-2 (hBD-2), S100A7 and LL-37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD-2 levels. No changes were noted in total leucocytes, C-reactive protein and erythrocyte sedimentation rate. These findings indicate that ustekinumab reduces psoriasis-related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation-related proteins.
Study Information
pubmed
2013
2013-05-01T00:00:00.000Z
10.1111/bjd.12175
19
34