Recipient HLA-G Single Nucleotide Polymorphisms Predict Post-Lung Development of Donor Specific Antibodies

Abstract

Purpose Human Leukocyte Antigen (HLA)-G is a class I - like molecule expressed by parenchymal cells and leukocytes. Higher HLA-G expression in recipients is associated with better transplant outcomes, and is modified by single nucleotide polymorphisms (SNPs). We hypothesized that donor and recipient HLA-G SNPs would predict development of de novo DSA (dnDSA) after lung transplantation (LT). Methods In a single center study, we examined 281 consecutive recipients and donors of a first bilateral LT between Jan 2008 and Dec 2011. Recipients were followed for a median of 4.985 years (interquartile range 2.6 - 6.24 yr). Eleven HLA-G SNPs were examined. All recipients were screened for class I and II HLA-Ab for the first two years. Sera with panel reactive antibody (PRA) greater than 0% were tested on single-antigen beads (SABs). HLA-Ab on SABs is typically identified at minimum normalized mean fluorescence intensity units greater than 1,200. A multivariable Cox proportional hazard model was used to assess associations of SNPs with dnDSA. Results In this cohort, 147 recipients (52.3%) developed dnDSA. Analysis adjusted for CMV mismatch status showed that 2 recipient SNPs, namely 3’UTR(3142) and 3’UTR(3196) increased risk of DSA by 84.7% (1.04 to 3.27) and by 94% (1.06 to 3.54), respectively, and none of donor SNP was associated with risk of dnDSA. Conclusion Recipient HLA-G SNPs are associated with development of dnDSA after LT. This is the first study to evaluate an association of donor HLA-G SNPs with the risk of development dnDSA after LTx. Human Leukocyte Antigen (HLA)-G is a class I - like molecule expressed by parenchymal cells and leukocytes. Higher HLA-G expression in recipients is associated with better transplant outcomes, and is modified by single nucleotide polymorphisms (SNPs). We hypothesized that donor and recipient HLA-G SNPs would predict development of de novo DSA (dnDSA) after lung transplantation (LT). In a single center study, we examined 281 consecutive recipients and donors of a first bilateral LT between Jan 2008 and Dec 2011. Recipients were followed for a median of 4.985 years (interquartile range 2.6 - 6.24 yr). Eleven HLA-G SNPs were examined. All recipients were screened for class I and II HLA-Ab for the first two years. Sera with panel reactive antibody (PRA) greater than 0% were tested on single-antigen beads (SABs). HLA-Ab on SABs is typically identified at minimum normalized mean fluorescence intensity units greater than 1,200. A multivariable Cox proportional hazard model was used to assess associations of SNPs with dnDSA. In this cohort, 147 recipients (52.3%) developed dnDSA. Analysis adjusted for CMV mismatch status showed that 2 recipient SNPs, namely 3’UTR(3142) and 3’UTR(3196) increased risk of DSA by 84.7% (1.04 to 3.27) and by 94% (1.06 to 3.54), respectively, and none of donor SNP was associated with risk of dnDSA. Recipient HLA-G SNPs are associated with development of dnDSA after LT. This is the first study to evaluate an association of donor HLA-G SNPs with the risk of development dnDSA after LTx.