HLA and risk of diffuse large B-cell lymphoma after solid organ transplantation
Published Date:Nov 2016
Pubmed Central ID:PMC4893345
Funding:U58 DP003931/DP/NCCDPHP CDC HHS/United States
K07 CA140360/CA/NCI NIH HHS/United States
HHSN261201000037C/CA/NCI NIH HHS/United States
N01PC35143/CA/NCI NIH HHS/United States
U58 DP003883/DP/NCCDPHP CDC HHS/United States
U58 DP003875/DP/NCCDPHP CDC HHS/United States
HHSN261201000036C/CA/NCI NIH HHS/United States
U58 DP003879/DP/NCCDPHP CDC HHS/United States
N01PC35137/CA/NCI NIH HHS/United States
HHSN261201300071C/CA/NCI NIH HHS/United States
U58 DP003920/DP/NCCDPHP CDC HHS/United States
HHSN261201300011C/RC/CCR NIH HHS/United States
U58 DP000807/DP/NCCDPHP CDC HHS/United States
N01PC35142/CA/NCI NIH HHS/United States
HHSN261201300021C/CA/NCI NIH HHS/United States
HHSN261201000035I/CA/NCI NIH HHS/United States
U58 DP000848/DP/NCCDPHP CDC HHS/United States
HHSN261201000024C/CA/NCI NIH HHS/United States
HHSN261201000034C/CA/NCI NIH HHS/United States
U58 DP003921/DP/NCCDPHP CDC HHS/United States
HHSN261201300011I/CA/NCI NIH HHS/United States
U58 DP000832/DP/NCCDPHP CDC HHS/United States
N01PC35139/CA/NCI NIH HHS/United States
U58 DP000824/DP/NCCDPHP CDC HHS/United States
Solid organ transplant recipients have heightened risk for diffuse large B-cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established.
We examined 172,231 U.S. kidney, heart, pancreas, and lung recipients transplanted between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number.
Compared to recipients who had two HLA-DR mismatches, those with zero or one mismatches had reduced DLBCL risk, (zero: IRR=0.76, 95%CI=0.61–0.95; one: IRR=0.83, 95%CI=0.69–1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset, DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all three loci (P=0.0003). Several individual recipient HLA-A, -B, -C, -DR, and –DQ antigens were also associated with DLBCL risk, including DR13 (IRR=0.74, 95%CI=0.57–0.93) and B38 (IRR=1.48, 95%CI=1.10–1.93), confirming prior findings that these two antigens are associated with risk of infection-associated cancers.
In conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients, or chronic immune stimulation.
Supporting Files:No Additional Files
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