The Presence of HLA-A Bw4-80I KIR Ligands Could Predict “Difficult-to-Treat” Psoriasis and Poor Response to Etanercept
Psoriasis is an immune-mediated dermatosis with a wide genetic predisposition. The immunogenetic background, specifically interactions between human leukocyte antigen (HLA) class I ligands and killer-cell immunoglobulin-like receptor (KIRs), have functional significance in modulating natural killer (NK) cells and can influence susceptibility and response to biological therapy.
The main aim of this study was to correlate HLA-A and -B KIR ligands with response to biological therapy in patients with psoriasis.
HLA-A and -B polymorphisms were determined in 48 patients (35 males and 13 females), with a mean of 22 years of disease (range 8–55). All patients were treated with biological therapy (adalimumab, etanercept, infliximab, or ustekinumab) for at least 6 months.
This study identifies, with statistical significance, the presence of at least one ligand HLA-A Bw4-80I in the “poor-responder” population (patients who needed two or more biologics) compared with the “responder” population (patients with good response after a single biological drug) (47.62 vs. 11.11%; p = 0.006) as well as in “non-responders to etanercept” compared with “responders to etanercept” (52.63 vs. 5%; p = 0.001).
Our preliminary results suggest that at least one ligand HLA-A Bw4-80I could be associated with “difficult-to-treat” psoriasis and that this ligand may reduce the probability of response to etanercept, producing more tumor necrosis factor (TNF)-α and neutralizing NK activity through a predominance of activating KIR. The ab initio identification of genetic markers of response to biologic therapy could improve the efficacy and economic impact of these agents.
Compliance with Ethical Standards
Conflict of interest
MG, AP, VB, RC, AP, IS, CK, RC, and VB have no conflicts of interest.
This study was funded by Ricerca corrente 17794/2014, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
Ethical approval and informed consent
The study was conducted according to the Declaration of Helsinki and STROBE statement and was approved by the IRCCS Policlinico San Matteo Foundation Ethics Committee. Each patient enrolled in the study provided informed consent.
- 5.Papp K, Menter A, Strober B, Kricorian G, Thompson EHZ, Milmont CE, et al. Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2015;72(3):436–439.e1.Google Scholar
- 12.Linares-Pineda TM, Cañadas-Garre M, Sánchez-Pozo A, et al. Gene polymorphisms as predictors of response to biological therapies in psoriasis patients. Pharmacol Res. 2016;113(Pt A):71–80.Google Scholar
- 15.Murdaca G, Gulli R, Spanò F, Lantieri F, Burlando M, Parodi A, Mandich P, Puppo F. TNF-α gene polymorphisms: association with disease susceptibility and response to anti-TNF-α treatment in psoriatic arthritis. J Invest Dermatol. 2014;134(10):2503–9. https://doi.org/10.1038/jid.2014.123 (epub 2014 Mar 4).CrossRefPubMedGoogle Scholar