<i>LIMS1</i> risk genotype and T cell-mediated rejection in kidney transplant recipients


Caliskan Y., Karahan G., Akgul S. U., Mirioglu Ş., Ozluk Y., Yazici H., ...Daha Fazla

NEPHROLOGY DIALYSIS TRANSPLANTATION, sa.11, ss.2120-2129, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1093/ndt/gfab168
  • Dergi Adı: NEPHROLOGY DIALYSIS TRANSPLANTATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.2120-2129
  • Anahtar Kelimeler: genetics, kidney transplantation, LIMS1, rejection, T cell-mediated rejection, GENOME-WIDE, ALLOGRAFT SURVIVAL, OUTCOMES
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background. This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. Methods. We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell-mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. Results. After a median follow-up of 11.4years, the rate of TCMR was higher in recipients with the GG genotype (n=200) compared with the AA/AG genotypes (n=641) [25 (12.5%) versus 35 (5.5%); P=0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44-4.12); P=0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan-Meier estimates of 5-year (94.3% versus 94.4%; P=0.99) and 10-year graft survival rates (86.9% versus 83.4%; P=0.31) did not differ significantly in the GG versus AA/AG groups. Conclusions. Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.