HLA Mismatching Favoring Host-Versus-Graft NK Cell Activity Via KIR3DL1 Is Associated With Improved Outcomes Following Lung Transplantation.
Am J Transplant
; 17(8): 2192-2199, 2017 Aug.
Article
de En
| MEDLINE
| ID: mdl-28375571
ABSTRACT
Chronic lung allograft dysfunction (CLAD) is linked to rejection and limits survival following lung transplantation. HLA-Bw4 recipients of HLA-Bw6 grafts have enhanced host-versus-graft (HVG) natural killer (NK) cell activity mediated by killer cell immunoglobulin-like receptor (KIR)3DL1 ligand. Because NK cells may promote tolerance by depleting antigen-presenting cells, we hypothesized improved outcomes for HLA-Bw4 recipients of HLA-Bw6 grafts. We evaluated differences in acute cellular rejection and CLAD-free survival across 252 KIR3DL1+ recipients from University of California, San Francisco (UCSF). For validation, we assessed survival and freedom from bronchiolitis obliterans syndrome (BOS), retransplantation, or death in 12 845 non-KIR typed recipients from the United Network for Organ Sharing (UNOS) registry. Cox proportional hazards models were adjusted for age, gender, ethnicity, transplant type, and HLA mismatching. HVG-capable subjects in the UCSF cohort had a decreased risk of CLAD or death (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.88) and decreased early lymphocytic bronchitis. The HVG effect was not significant in subjects with genotypes predicting low KIR3DL1 expression. In the UNOS cohort, HVG-capable subjects had a decreased risk of BOS, retransplant, or death (HR 0.95, 95% CI 0.91-0.99). Survival improved with the higher-affinity Bw4-80I ligand and in Bw4 homozygotes. Improved outcomes in HVG-capable recipients are consistent with a protective NK cell role. Augmentation of NK activity could supplement current immunosuppression techniques.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules tueuses naturelles
/
Antigènes HLA-B
/
Transplantation pulmonaire
/
Récepteur KIR3DL1
/
Survie du greffon
/
Histocompatibilité
/
Cellules présentatrices d'antigène
Type d'étude:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Am J Transplant
Sujet du journal:
TRANSPLANTE
Année:
2017
Type de document:
Article
Pays d'affiliation:
Canada