TY - JOUR
T1 - HLA and Risk of Diffuse Large B cell Lymphoma after Solid Organ Transplantation
AU - Hussain, Shehnaz K.
AU - Makgoeng, Solomon B.
AU - Everly, Matthew J.
AU - Goodman, Marc T.
AU - Martínez-Maza, Otoniel
AU - Morton, Lindsay M.
AU - Clarke, Christina A.
AU - Lynch, Charles F.
AU - Snyder, Jon
AU - Israni, Ajay
AU - Kasiske, Bertram L.
AU - Engels, Eric A.
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Background 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. Methods We examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States 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. Results Compared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [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 3 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 2 antigens are associated with risk of infection-associated cancers. Conclusions 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.
AB - Background 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. Methods We examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States 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. Results Compared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [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 3 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 2 antigens are associated with risk of infection-associated cancers. Conclusions 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.
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U2 - 10.1097/TP.0000000000001025
DO - 10.1097/TP.0000000000001025
M3 - Article
C2 - 26636741
AN - SCOPUS:84949438958
SN - 0041-1337
VL - 100
SP - 2453
EP - 2460
JO - Transplantation
JF - Transplantation
IS - 11
ER -