PMID- 29943154
OWN - NLM
STAT- MEDLINE
DCOM- 20181214
LR  - 20190207
IS  - 1179-2000 (Electronic)
IS  - 1177-1062 (Linking)
VI  - 22
IP  - 4
DP  - 2018 Aug
TI  - The Presence of HLA-A Bw4-80I KIR Ligands Could Predict "Difficult-to-Treat" 
      Psoriasis and Poor Response to Etanercept.
PG  - 471-474
LID - 10.1007/s40291-018-0345-9 [doi]
AB  - 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)-alpha 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.
FAU - Guarene, M
AU  - Guarene M
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Pasi, A
AU  - Pasi A
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Bolcato, V
AU  - Bolcato V
AD  - Institute of Dermatology, IRCCS Policlinico San Matteo Foundation, University of 
      Pavia, Piazzale Golgi, 2, 27100, Pavia, Italy.
FAU - Cananzi, R
AU  - Cananzi R
AD  - Institute of Dermatology, IRCCS Policlinico San Matteo Foundation, University of 
      Pavia, Piazzale Golgi, 2, 27100, Pavia, Italy.
FAU - Piccolo, A
AU  - Piccolo A
AD  - Unit of Anatomic Pathology, Department of Molecular Medicine, IRCCS Policlinico 
      San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Sbarsi, I
AU  - Sbarsi I
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Klersy, C
AU  - Klersy C
AD  - Clinical Epidemiology and Biometric Unit, IRCCS Policlinico San Matteo 
      Foundation, University of Pavia, Pavia, Italy.
FAU - Cacciatore, R
AU  - Cacciatore R
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Brazzelli, Valeria
AU  - Brazzelli V
AUID- ORCID: 0000-0001-5898-6448
AD  - Institute of Dermatology, IRCCS Policlinico San Matteo Foundation, University of 
      Pavia, Piazzale Golgi, 2, 27100, Pavia, Italy. vbrazzelli@libero.it.
LA  - eng
GR  - 17794/2014/Ricerca corrente , IRCCS Policlinico San Matteo Foundation, University 
      of Pavia, Pavia, Italy./International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Mol Diagn Ther
JT  - Molecular diagnosis & therapy
JID - 101264260
RN  - 0 (Biological Products)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (Receptors, KIR)
RN  - B72HH48FLU (Infliximab)
RN  - FU77B4U5Z0 (Ustekinumab)
RN  - FYS6T7F842 (Adalimumab)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adalimumab/therapeutic use
MH  - Adolescent
MH  - Adult
MH  - Biological Products/*therapeutic use
MH  - Child
MH  - Etanercept/therapeutic use
MH  - Female
MH  - HLA-A Antigens/*genetics
MH  - HLA-B Antigens
MH  - Humans
MH  - Infliximab/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Psoriasis/*drug therapy/genetics/immunology
MH  - Receptors, KIR/immunology
MH  - Sequence Analysis, DNA/*methods
MH  - Treatment Outcome
MH  - Ustekinumab/therapeutic use
MH  - Young Adult
EDAT- 2018/06/27 06:00
MHDA- 2018/12/15 06:00
CRDT- 2018/06/27 06:00
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2018/12/15 06:00 [medline]
PHST- 2018/06/27 06:00 [entrez]
AID - 10.1007/s40291-018-0345-9 [pii]
AID - 10.1007/s40291-018-0345-9 [doi]
PST - ppublish
SO  - Mol Diagn Ther. 2018 Aug;22(4):471-474. doi: 10.1007/s40291-018-0345-9.