PMID- 31249568
OWN - NLM
STAT- MEDLINE
DCOM- 20201020
LR  - 20201020
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and 
      Patients' Survival After Lung Transplant.
PG  - 1208
LID - 10.3389/fimmu.2019.01208 [doi]
LID - 1208
AB  - Fc gamma receptors (FcgammaRs) play a major role in the regulation of humoral immune 
      responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A can impact 
      the expression level, IgG affinity and function of the CD32 and CD16 FcgammaRs in 
      response to their engagement by the Fc fragment of IgG. The CD16 isoform encoded 
      by FCGR3A [158V/V] controls the intensity of antibody-dependent cytotoxic 
      alloimmune responses of natural killer cells (NK) and has been identified as a 
      susceptibility marker predisposing patients to cardiac allograft vasculopathy 
      after heart transplant. This study aimed to investigate whether FCGR2A and FCGR3A 
      polymorphisms can also be associated with the clinical outcome of lung transplant 
      recipients (LTRs). The SNPs of FCGR2A ([131R/H], rs1801274) and FCGR3A ([158V/F], 
      rs396991) were identified in 158 LTRs and 184 Controls (CTL). The corresponding 
      distribution of genotypic and allelic combinations was analyzed for potential 
      links with the development of circulating donor-specific anti-HLA alloantibodies 
      (DSA) detected at months 1 and 3 after lung transplant (LTx), the occurrence of 
      acute rejection (AR) and chronic lung allograft dysfunction (CLAD), and the 
      overall survival of LTRs. The FCGR3A [158V/V] genotype was identified as an 
      independent susceptibility factor associated with higher rates of AR during the 
      first trimester after LTx (HR 4.8, p < 0.0001, 95% CI 2.37-9.61), but it could 
      not be associated with the level of CD16- mediated NK cell activation in response 
      to the LTR's DSA, whatever the MFI intensity and C1q binding profiles of the DSA 
      evaluated. The FCGR2A [131R/R] genotype was associated with lower CLAD-free 
      survival of LTRs, independently of the presence of DSA at 3 months (HR 1.8, p = 
      0.024, 95% CI 1.08-3.03). Our data indicate that FCGR SNPs differentially affect 
      the clinical outcome of LTRs and may be of use to stratify patients at higher 
      risk of experiencing graft rejection. Furthermore, these data suggest that in the 
      LTx setting, specific mechanisms of humoral alloreactivity, which cannot be 
      solely explained by the complement and CD16-mediated pathogenic effects of DSA, 
      may be involved in the development of acute and chronic lung allograft rejection.
FAU - Paul, Pascale
AU  - Paul P
AD  - Department of Hematology, Hopital de la Conception, INSERM CIC-1409, Assistance 
      Publique-Hopitaux Marseille (AP-HM), Marseille, France.
AD  - INSERM 1263, INRA, C2VN, Aix-Marseille Universite (AMU), INSERM, Marseille, 
      France.
FAU - Pedini, Pascal
AU  - Pedini P
AD  - Etablissement Francais du Sang PACA-Corse 13005, Marseille, France.
FAU - Lyonnet, Luc
AU  - Lyonnet L
AD  - Department of Hematology, Hopital de la Conception, INSERM CIC-1409, Assistance 
      Publique-Hopitaux Marseille (AP-HM), Marseille, France.
FAU - Di Cristofaro, Julie
AU  - Di Cristofaro J
AD  - "Biologie des Groupes Sanguins", UMR 7268 ADES Aix-Marseille Universite/EFS/CNRS, 
      Marseille, France.
FAU - Loundou, Anderson
AU  - Loundou A
AD  - Departement de sante Publique - EA 3279, Assistance Publique-Hopitaux Marseille 
      (AP-HM), Aix-Marseille Universite, Marseille, France.
FAU - Pelardy, Mathieu
AU  - Pelardy M
AD  - Etablissement Francais du Sang PACA-Corse 13005, Marseille, France.
FAU - Basire, Agnes
AU  - Basire A
AD  - Etablissement Francais du Sang PACA-Corse 13005, Marseille, France.
FAU - Dignat-George, Francoise
AU  - Dignat-George F
AD  - Department of Hematology, Hopital de la Conception, INSERM CIC-1409, Assistance 
      Publique-Hopitaux Marseille (AP-HM), Marseille, France.
AD  - INSERM 1263, INRA, C2VN, Aix-Marseille Universite (AMU), INSERM, Marseille, 
      France.
FAU - Chiaroni, Jacques
AU  - Chiaroni J
AD  - Etablissement Francais du Sang PACA-Corse 13005, Marseille, France.
AD  - "Biologie des Groupes Sanguins", UMR 7268 ADES Aix-Marseille Universite/EFS/CNRS, 
      Marseille, France.
FAU - Thomas, Pascal
AU  - Thomas P
AD  - Service de Chirurgie Thoracique et Transplantation Pulmonaire, CHU Nord 
      Assistance Publique-Hopitaux Marseille (AP-HM), Aix-Marseille Universite, 
      Marseille, France.
FAU - Reynaud-Gaubert, Martine
AU  - Reynaud-Gaubert M
AD  - Service de Pneumologie et Transplantation Pulmonaire, CHU Nord Assistance 
      Publique-Hopitaux Marseille (AP-HM) - IHU Mediterranee Infection 
      Aix-Marseille-Universite, Marseille, France.
FAU - Picard, Christophe
AU  - Picard C
AD  - Etablissement Francais du Sang PACA-Corse 13005, Marseille, France.
AD  - "Biologie des Groupes Sanguins", UMR 7268 ADES Aix-Marseille Universite/EFS/CNRS, 
      Marseille, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190612
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (FCGR2A protein, human)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Biomarkers/metabolism
MH  - Chronic Disease
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - Gene Frequency
MH  - *Genotype
MH  - Graft Rejection/*genetics/immunology/mortality
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Isoantibodies/metabolism
MH  - Killer Cells, Natural/*immunology
MH  - Lung Transplantation
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, IgG/*genetics
MH  - Survival Analysis
PMC - PMC6582937
OTO - NOTNLM
OT  - Fc-gamma receptors
OT  - HLA antibodies
OT  - allograft rejection
OT  - chronic lung allograft dysfunction
OT  - lung transplantation
OT  - natural killer cells
EDAT- 2019/06/30 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/01/01
CRDT- 2019/06/29 06:00
PHST- 2019/02/19 00:00 [received]
PHST- 2019/05/13 00:00 [accepted]
PHST- 2019/06/29 06:00 [entrez]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01208 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jun 12;10:1208. doi: 10.3389/fimmu.2019.01208. eCollection 
      2019.