For broad-split groups where the broad antigen was very rare, we excluded the broad antigen and analyzed each child antigen as their own category.

Transcription

1 Description of categorization of broad and split antigens HLA antigen classifications have evolved over time as assay development has allowed the detection of differences in antigens ( split categories) that were previously undistinguishable ( broad categories). Our study included 21 groups of antigens that were affected by broad categories splitting over time. For broad-split groups where the broad antigen was very rare, we excluded the broad antigen and analyzed each child antigen as their own category. A9 Broad (Splits A23 and A24) A10 Broad (Splits A25, A26, A34, and A66) A19 Broad (Splits A29, A30, A31, A32, A33, and A74) B5 Broad (Splits B51 and B52) B12 Broad (Splits B44 and B45) B15 Broad (Splits B62, B63, and B75) B16 Broad (Splits B38 and B39) B17 Broad (Splits B57 and B58) B21 Broad (Splits B49 and B50) B22 Broad (Splits B55 and B56) B40 Broad (Splits B60 and B61) When one or more split antigens were very rare, we combined the splits with the broad antigen for each group to aggregate the data for analysis. A28 Broad (Splits A68 and A69) B14 Broad (Splits B64 and B65) B70 Broad (Splits B71 and B72) C3 Broad (Splits C9 and C10) There were 6 antigen groups where there appeared to be gradual phase out of the broad categories and phase in of the split categories over time. For these groups, we examined the

2 prevalence trends over time. We excluded the broad categories from analysis, and included the split categories for transplants occurring on or after the year at which there was at least twothirds (67%) of the phase in of the split category had been achieved. DR2 Broad (Splits DR15 and DR16; 1995) DR5 Broad (Splits DR11 and DR12; 1991) DR6 Broad (Splits DR13 and DR14; 1995) DR3 Broad (Splits DR17 and DR18; 1995) DQ1 Broad (Splits DQ5 and DQ6; 1995) DQ3 Broad (Splits DQ7, DQ8, and DQ9; 1995)

3 1 Table S1. Associations between HLA mismatch and diffuse large B-cell lymphoma among kidney transplant recipients (only) Antigen Mismatch number recipients with DLBCL n (%) n (%) recipients without DLBCL SIR IRR a 95% CI P for trend A (25.05) 30,236 (22.79) ( ) (44.10) 56,650 (42.70) ( ) (30.67) 45,196 (34.06) reference B (19.96) 25,213 (19.00) ( ) (44.10) 51,717 (38.98) ( ) (35.75) 55,153 (41.57) reference DR (23.96) 31,841 (24.00) ( ) (46.10) 62,765 (47.31) ( ) (29.22) 37,187 (28.03) reference A+B+DR 0 60 (10.89) 14,423 (10.87) ( ) (6.53) 7,036 (5.30) ( ) 2 71 (12.89) 15,329 (11.55) ( ) (21.78) 27,624 (20.82) ( ) (21.23) 26,616 (20.06) ( ) 5 88 (15.97) 27,336 (20.60) ( ) 6 58 (10.53) 13,749 (10.36) reference SIR=Standardized incidence ratio; IRR=Incidence rate ratio a IRRs were calculated as the ratio of incidence rates between each category of mismatch and the reference mismatch category, and were adjusted for sex, age at transplant, race/ethnicity, year of transplant, transplanted organ, transplant number, panel reactive antibody score, and donor vital status.

4 2 Table S2. Associations between HLA mismatch and early- and late-onset diffuse large B-cell lymphoma among kidney transplant recipients (only) Early-onset DLBCL ( 2 years after transplantation) Late-onset DLBCL (> 2 years after transplantation) Antigen Mismatch number IRR * 95%CI P for trend IRR a 95%CI P for trend A ( ) ( ) ( ) 0.89 ( ) reference 1.00 reference B ( ) ( ) ( ) 0.88 ( ) reference 1.00 reference DR ( ) ( ) reference A+B+DR ( ) ( ) ( ) ( ) ( ) ( ) reference -- DLBCL=Diffuse large B-cell lymphoma; IRR=Incidence rate ratio a IRRs were calculated as the ratio of incidence rates between each category of mismatch and the reference mismatch category, and were adjusted for sex, age at transplant, race/ethnicity, year of transplant, transplanted organ, transplant number, panel reactive antibody score, and donor vital status.

5 3 Table S3. Associations between HLA antigens and diffuse large B-cell lymphoma Antigen recipients with DLBCL n (%) n (%) recipients without DLBCL SIR IRR a 95% CI P value HLA-A A3 232 (25.72) 35,116 (20.50) ( ) A28 + A68 + A (12.75) 20,160 (11.77) ( ) A32 36 (3.99) 8,876 (5.18) ( ) A25 18 (2.00) 4,491 (2.62) ( ) A33 32 (3.55) 10,340 (6.04) ( ) A66 3 (0.33) 1,857 (1.08) ( ) A2 417 (46.23) 78,722 (45.95) ( ) A1 235 (26.05) 37,938 (22.14) ( ) A23 46 (5.10) 12,952 (7.56) ( ) A11 94 (10.42) 17,906 (10.45) ( ) A36 4 (0.44) 2,056 (1.20) ( ) A30 77 (8.54) 17,258 (10.07) ( ) A74 8 (0.89) 3,452 (2.01) ( ) A31 51 (5.65) 9,155 (5.34) ( ) A29 65 (7.21) 11,711 (6.84) ( ) A34 14 (1.55) 4,133 (2.41) ( ) A (17.96) 30,396 (17.74) ( ) A26 58 (6.43) 10,140 (5.92) ( ) HLA-B B38 53 (5.88) 6,680 (3.90) ( ) B58 13 (1.44) 7,405 (4.32) ( ) B (11.09) 14,613 (8.53) ( ) B48 2 (0.22) 2,000 (1.17) ( ) B55 15 (1.66) 4,177 (2.44) ( ) B41 10 (1.11) 3,642 (2.13) ( ) B70 + B71 + B72 37 (4.10) 8,343 (4.87) ( ) B63 7 (0.78) 3,109 (1.81) ( ) B7 195 (21.62) 31,070 (18.13) ( ) B47 1 (0.11) 744 (0.43) ( ) B46 8 (0.89) 946 (0.55) ( ) B57 43 (4.77) 10,685 (6.24) ( ) B42 8 (0.89) 4,603 (2.69) ( ) B51 93 (10.31) 15,441 (9.01) ( ) B75 3 (0.33) 1,380 (0.81) ( ) B52 17 (1.88) 4,743 (2.77) ( ) B39 38 (4.21) 9,166 (5.35) ( ) B (21.06) 34,926 (20.39) ( ) B8 184 (20.40) 29,753 (17.37) ( )

6 4 B49 35 (3.88) 6,678 (3.90) ( ) B13 33 (3.66) 6,396 (3.73) ( ) B78 1 (0.11) 632 (0.37) ( ) B27 64 (7.10) 10,104 (5.90) ( ) B56 11 (1.22) 1,754 (1.02) ( ) B14 + B64 + B65 67 (7.43) 11,692 (6.82) ( ) B45 24 (2.66) 5,880 (3.43) ( ) B50 19 (2.11) 4,090 (2.39) ( ) B (17.74) 31,201 (18.21) ( ) B53 31 (3.44) 9,941 (5.80) ( ) B61 28 (3.10) 6,387 (3.73) ( ) B37 20 (2.22) 3,364 (1.96) ( ) B60 86 (9.53) 14,180 (8.28) ( ) B (11.09) 16,903 (9.87) ( ) B (0.57) HLA-C C8 21 (2.33) 8,035 (4.69) ( ) C12 11 (1.22) 2,245 (1.31) ( ) C3 + C9 + C (13.86) 27,215 (15.88) ( ) C7 251 (27.83) 46,553 (27.17) ( ) C5 84 (9.31) 13,196 (7.70) ( ) C6 70 (7.76) 16,335 (9.53) ( ) C15 5 (0.55) 1,396 (0.81) ( ) C4 146 (16.19) 29,767 (17.37) ( ) C100 3 (0.33) 1,627 (0.95) ( ) C2 58 (6.43) 11,739 (6.85) ( ) C16 6 (0.67) 2,476 (1.45) ( ) C1 41 (4.55) 7,805 (4.56) ( ) C (0.46) C ,656 (0.97) HLA-DQ DQ7 b 98 (15.86) 29,725 (20.88) ( ) DQ8 b 64 (10.36) 15,031 (10.56) ( ) DQ5 b 92 (14.89) 22,526 (15.82) ( ) DQ2 281 (31.15) 56,657 (33.07) ( ) DQ6 b 116 (18.77) 32,607 (22.91) ( ) DQ9 b 19 (3.07) 3,896 (2.74) ( ) DQ4 51 (5.65) 13,461 (7.86) ( ) HLA-DR DR13 b 96 (15.53) 29,321 (20.60) ( ) DR17 b 112 (18.12) 22,562 (15.85) ( ) DR9 20 (2.22) 6,208 (3.62) ( ) DR7 163 (18.07) 33,210 (19.38) ( )

7 5 DR4 294 (32.59) 54,989 (32.10) ( ) DR10 23 (2.55) 4,170 (2.43) ( ) DR1 159 (17.63) 26,250 (15.32) ( ) DR16 b 13 (2.10) 4,327 (3.04) ( ) DR15 b 131 (21.20) 29,482 (20.71) ( ) DR18 b 4 (0.65) 3,093 (2.17) ( ) DR12 b 33 (3.89) 8,098 (4.89) ( ) DR11 b 141 (16.63) 29,680 (17.92) ( ) DR8 73 (8.09) 16,037 (9.36) ( ) DR103 7 (0.78) 1,492 (0.87) ( ) DR14 b 41 (6.63) 9,048 (6.36) ( ) DLBCL=Diffuse large B-cell lymphoma; SIR=Standardized incidence ratio; IRR=Incidence rate ratio a IRRs were calculated as the ratio of incidence rates between each antigen category and all other antigens combined, and were adjusted for sex, age at transplant, race/ethnicity, year of transplant, transplanted organ, and transplant number. b This category includes restricted transplant years reflecting when the split antigen category was in common use (described in supplementary materials).

8 6 Table S4. Associations between HLA antigens and diffuse large B-cell lymphoma among kidney transplant recipients (only) Antigen recipients with DLBCL n (%) n (%) recipients without DLBCL SIR IRR a 95% CI P value HLA-A A28 + A68 + A69 79 (14.34) 16,283 (12.27) ( ) A32 19 (3.45) 6,625 (4.99) ( ) A25 10 (1.81) 3,330 (2.51) ( ) A33 22 (3.99) 8,658 (6.53) ( ) A3 125 (22.69) 26,337 (19.85) ( ) A36 4 (0.73) 1,806 (1.36) ( ) A2 252 (45.74) 60,242 (45.40) ( ) A29 40 (7.26) 8,858 (6.68) ( ) A34 12 (2.18) 3,593 (2.71) ( ) A23 32 (5.81) 10,694 (8.06) ( ) A66 3 (0.54) 1,528 (1.15) ( ) A26 36 (6.53) 7,890 (5.95) ( ) A11 68 (12.34) 14,104 (10.63) ( ) A1 131 (23.77) 27,743 (20.91) ( ) A74 7 (1.27) 2,953 (2.23) ( ) A (18.33) 23,647 (17.82) ( ) A31 30 (5.44) 7,304 (5.50) ( ) A30 46 (8.35) 14,054 (10.59) ( ) HLA-B B38 36 (6.53) 5,300 (3.99) ( ) B58 8 (1.45) 6,209 (4.68) ( ) B46 8 (1.45) 852 (0.64) ( ) B41 5 (0.91) 2,854 (2.15) ( ) B63 3 (0.54) 2,558 (1.93) ( ) B57 24 (4.36) 8,368 (6.31) ( ) B55 8 (1.45) 3,191 (2.41) ( ) B18 60 (10.89) 10,954 (8.26) ( ) B48 2 (0.36) 1,795 (1.35) ( ) B7 117 (21.23) 23,659 (17.83) ( ) B70 + B71 + B72 26 (4.72) 7,024 (5.29) ( ) B75 2 (0.36) 1,272 (0.96) ( ) B49 25 (4.54) 5,300 (3.99) ( ) B52 10 (1.81) 3,957 (2.98) ( ) B56 9 (1.63) 1,368 (1.03) ( ) B14 + B64 + B65 43 (7.80) 9,037 (6.81) ( ) B42 7 (1.27) 4,027 (3.04) ( ) B47 1 (0.18) 514 (0.39) ( ) B8 107 (19.42) 21,284 (16.04) ( ) B62 53 (9.62) 12,366 (9.32) ( )

9 7 B60 46 (8.35) 10,565 (7.96) ( ) B50 10 (1.81) 3,141 (2.37) ( ) B27 37 (6.72) 7,535 (5.68) ( ) B39 24 (4.36) 7,288 (5.49) ( ) B (19.42) 24,820 (18.71) ( ) B45 13 (2.36) 4,855 (3.66) ( ) B (21.05) 26,247 (19.78) ( ) B37 12 (2.18) 2,524 (1.90) ( ) B61 19 (3.45) 5,313 (4.00) ( ) B51 52 (9.44) 12,043 (9.08) ( ) B13 22 (3.99) 4,861 (3.66) ( ) B53 24 (4.36) 8,563 (6.45) ( ) B (0.42) B (0.64) HLA-C C12 8 (1.45) 1,650 (1.24) ( ) C7 155 (28.13) 35,420 (26.70) ( ) C3 + C9 + C10 74 (13.43) 20,654 (15.57) ( ) C8 18 (3.27) 6,463 (4.87) ( ) C16 1 (0.18) 1,859 (1.40) ( ) C100 1 (0.18) 1,430 (1.08) ( ) C15 1 (0.18) 1,064 (0.80) ( ) C2 39 (7.08) 9,251 (6.97) ( ) C6 45 (8.17) 12,595 (9.49) ( ) C5 44 (7.99) 9,614 (7.25) ( ) C4 91 (16.52) 24,159 (18.21) ( ) C1 29 (5.26) 6,206 (4.68) ( ) C (0.45) C ,348 (1.02) HLA-DQ DQ7 b 63 (16.41) 23,989 (21.69) ( ) DQ5 b 60 (15.63) 17,705 (16.01) ( ) DQ8 b 38 (9.90) 11,047 (9.99) ( ) DQ9 b 11 (2.86) 2,969 (2.68) ( ) DQ2 169 (30.67) 42,501 (32.03) ( ) DQ4 34 (6.17) 11,184 (8.43) ( ) DQ6 b 78 (20.31) 26,114 (23.61) ( ) HLA-DR DR13 b 58 (15.10) 23,247 (21.02) ( ) DR15 b 91 (23.70) 23,720 (21.45) ( ) DR7 99 (17.97) 25,509 (19.23) ( ) DR17 b 61 (15.89) 16,262 (14.71) ( ) DR1 94 (17.06) 19,828 (14.94) ( ) DR10 15 (2.72) 3,441 (2.59) ( ) DR18 4 (1.04) 2,695 (2.44) ( ) DR12 b 24 (4.58) 6,809 (5.31) ( )

10 8 DR16 b 9 (2.34) 3,428 (3.10) ( ) DR4 172 (31.22) 40,623 (30.62) ( ) DR14 b 26 (6.77) 7,525 (6.80) ( ) DR9 17 (3.09) 4,931 (3.72) ( ) DR11 90 (17.18) 23,815 (18.57) ( ) DR8 46 (8.35) 13,176 (9.93) ( ) DR103 4 (0.73) 1,153 (0.87) ( ) DLBCL=Diffuse large B-cell lymphoma; SIR=Standardized incidence ratio; IRR=Incidence rate ratio a IRRs were calculated as the ratio of incidence rates between each antigen category and all other antigens combined, and were adjusted for sex, age at transplant, race/ethnicity, year of transplant, transplanted organ, transplant number, panel reactive antibody score, and donor vital status. b This category includes restricted transplant years reflecting when the split antigen category was in common use (described in supplementary materials).