PMID- 32189206
OWN - NLM
STAT- MEDLINE
DCOM- 20210601
LR  - 20210601
IS  - 1179-2000 (Electronic)
IS  - 1177-1062 (Linking)
VI  - 24
IP  - 3
DP  - 2020 Jun
TI  - Reduced Efficacy of Biological Drugs in Psoriatic Patients with HLA-A Bw4-80I KIR 
      Ligands.
PG  - 311-314
LID - 10.1007/s40291-020-00457-8 [doi]
AB  - BACKGROUND: Biological drugs (biologics) are a highly effective therapy for the 
      moderate to severe form of psoriasis, an immune-mediated dermatosis with a strong 
      immunogenetic component. The interaction between human leukocyte antigen (HLA) 
      class I ligands and killer immunoglobulin-like receptors (KIR) has a functional 
      significance in the education of natural killer (NK) cells, and can thus 
      influence the response to biologics. OBJECTIVE: In this study, we investigated 
      the impact of HLA-A and -B KIR ligands in the response to biologics in a cohort 
      of psoriatic patients. METHODS: Eighty-five patients with moderate to severe 
      psoriasis treated with biologics (adalimumab, etanercept, infliximab, ustekinumab 
      and secukinumab) were enrolled in the study. Clinical response was evaluated as 
      patients attaining 50%, 75% or 90% reduction in the Psoriasis Area and Severity 
      Index (PASI) (PASI 50, 75 or 90, respectively) over 6 months' follow-up. Poor 
      response was defined as PASI 50, and in this case patients shifted to treatment 
      with a different biologic. Fifty-two patients (61.2%) showed excellent response 
      (PASI 90) to the first biologic, while 33 patients (38.8%), needed two or more 
      biologics before reaching an excellent response (PASI 90) and were considered 
      difficult to treat. RESULTS: Only HLA-A Bw4-80I ligands were associated with the 
      response to biologics; in particular, they were linked with reduced response both 
      at univariable analysis (odds ratio [OR] 3.11, 95% confidence interval [CI] 
      1.19-8.07; p = 0.019) and multivariable analysis (OR 5.02, 95% CI 1.40-17.97; 
      p = 0.013). CONCLUSION: We suggest that the HLA-A Bw4-80I epitope could be a 
      marker of reduced responsiveness to biologics. The possible reason for this is an 
      increase of tumour necrosis factor (TNF)-alpha and the silencing of NK cells through 
      the predominant interaction with the KIR3DL/S pair. HLA-KIR affinities might lead 
      to a more efficient way to prescribe biologics.
FAU - Bolcato, Vittorio
AU  - Bolcato V
AD  - Department of Public Health, Experimental and Forensic Medicine, University of 
      Pavia, Pavia, Italy.
FAU - Pasi, Annamaria
AU  - Pasi A
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Cacciatore, Rosalia
AU  - Cacciatore R
AD  - Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS 
      Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
FAU - Klersy, Catherine
AU  - Klersy C
AD  - Clinical Epidemiology and Biometric Unit, 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
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 (Ligands)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biological Products/pharmacology/*therapeutic use
MH  - Female
MH  - HLA-A Antigens/*immunology
MH  - Humans
MH  - Ligands
MH  - Male
MH  - Middle Aged
MH  - Psoriasis/*drug therapy/*etiology/*metabolism
MH  - Receptors, KIR/*metabolism
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2020/03/20 06:00
MHDA- 2021/06/02 06:00
CRDT- 2020/03/20 06:00
PHST- 2020/03/20 06:00 [pubmed]
PHST- 2021/06/02 06:00 [medline]
PHST- 2020/03/20 06:00 [entrez]
AID - 10.1007/s40291-020-00457-8 [pii]
AID - 10.1007/s40291-020-00457-8 [doi]
PST - ppublish
SO  - Mol Diagn Ther. 2020 Jun;24(3):311-314. doi: 10.1007/s40291-020-00457-8.