HLA-C matching and liver transplants: donor-recipient genotypes influence early outcome and CD8+KIR2D+ T-cells recuperation.
BACKGROUND
Fully human leukocyte antigens (HLA)-mismatched liver grafts are well accepted, but the HLA influence on acceptance or rejection is unclear and much less so the impact of HLA-C, which may be conditioned by the fact that HLA-C-encode molecules are the major ligands for killer cell immunoglobulin-like receptors (KIR).


METHODS
The HLA-C allele compatibility and the effect of donor and recipient HLA-C genotype on early liver graft acceptance and on CD8KIR T-cells recuperation were analyzed in a series of 431 primary liver transplants. Standard polymerase chain reaction PCR-SSO was used for HLA-C typing and flow cytometry to identify T cells KIR positives. Transplants were classified into two groups: acute rejection and nonacute rejection, and individual HLA-C genotypes as C1/C1, C2/C2, and C1/C2.


RESULTS
A favorable effect of HLA-C allelic compatibility on early liver graft acceptance was found because acute rejection significantly increased in transplants performed with 2 HLA-C allele mismatches (P=0.02). Considering the HLA-C groups, it was observed that C1/C2 heterozygous donors were best accepted in C1/C1 patients than in C2/C2 recipients, who experienced a high rate of acute rejection (P<0.004 and P<0.005, respectively). In addition, after transplantation CD3CD8KIR2D T-cells repertoires significantly increased in C1/C1 and C1/C2, but not in C2/C2 patients.


CONCLUSIONS
This study confirms the benefit of HLA-C allele matching on early liver transplant outcome and shows that donor HLA-C heterozygosis influences the alloresponse of C1 and C2 homozygous patients and the recuperation of CD3CD8KIR2D T cells, suggesting an involvement in liver graft tolerance.
López-Alvarez
Maria R
MR
Immunology Service, and Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), University Hospital Virgen de la Arrixaca, El Palmar, Murcia. mdrocio.alvarez@carm.es
Moya-Quiles
María R
MR
Minguela
Alfredo
A
Gil
Juana
J
Miras
Manuel
M
Campillo
José A
JA
Díaz-Alderete
María A
MA
García-Alonso
Ana M
AM
Sánchez-Bueno
Francisco
F
Vicario
Jose L
JL
Muro
Manuel
M
Alvarez-López
María R
MR
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D006580:Genetic Carrier Screening; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D054340:Receptors, KIR / Q000276:immunology*; D014019:Tissue Donors / Q000706:statistics & numerical data*
D006680:HLA Antigens; D015236:HLA-C Antigens; D007166:Immunosuppressive Agents; D054340:Receptors, KIR; D004247:DNA