The Presence of HLA-A Bw4-80I KIR Ligands Could Predict “Difficult-to-Treat” Psoriasis and Poor Response to Etanercept

M. Guarene, A. Pasi, V. Bolcato, R. Cananzi, A. Piccolo, I. Sbarsi, C. Klersy, R. Cacciatore, Valeria Brazzelli

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Objective: The main aim of this study was to correlate HLA-A and -B KIR ligands with response to biological therapy in patients with psoriasis. Methods: 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. Results: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)1-4
Number of pages4
JournalMolecular Diagnosis and Therapy
DOIs
Publication statusAccepted/In press - Jun 25 2018
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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