Multivariable analysis of impact of amino acid substitution on HLA class I molecules for severe aGVHD
| Posisiton and kind of amino acid substitution, donor-recipient . | HS . | N . | Event† . | HR (95% CI) . | P . |
|---|---|---|---|---|---|
| HLA-A locus | |||||
| Tyr9A-Phe9A | 4.1 | 163 | 64 | 1.66 (1.19-2.32) | .003 |
| Asn116A-Asp116A | 0 | 32 | 15 | 2.25 (1.26-4.01) | .005* |
| HLA-C locus | |||||
| Tyr9C-Ser9C | 0.5 | 146 | 59 | 1.66 (1.23-2.25) | .001 |
| Asn77C-Ser77C | 2.7 | 205 | 90 | 1.87 (1.46-2.39) | < .001 |
| Lys80C-Asn80C | 0.4 | 205 | 90 | 1.87 (1.46-2.39) | < .001 |
| Tyr99C-Phe99C | 4.1 | 146 | 59 | 1.64 (1.21-2.22) | .001 |
| Leu116C-Ser116C | 4.6 | 53 | 30 | 3.40 (2.20-5.25) | < .001 |
| Arg156C-Leu156C | 8.3 | 251 | 88 | 1.48 (1.15-1.90) | .002 |
| Posisiton and kind of amino acid substitution, donor-recipient . | HS . | N . | Event† . | HR (95% CI) . | P . |
|---|---|---|---|---|---|
| HLA-A locus | |||||
| Tyr9A-Phe9A | 4.1 | 163 | 64 | 1.66 (1.19-2.32) | .003 |
| Asn116A-Asp116A | 0 | 32 | 15 | 2.25 (1.26-4.01) | .005* |
| HLA-C locus | |||||
| Tyr9C-Ser9C | 0.5 | 146 | 59 | 1.66 (1.23-2.25) | .001 |
| Asn77C-Ser77C | 2.7 | 205 | 90 | 1.87 (1.46-2.39) | < .001 |
| Lys80C-Asn80C | 0.4 | 205 | 90 | 1.87 (1.46-2.39) | < .001 |
| Tyr99C-Phe99C | 4.1 | 146 | 59 | 1.64 (1.21-2.22) | .001 |
| Leu116C-Ser116C | 4.6 | 53 | 30 | 3.40 (2.20-5.25) | < .001 |
| Arg156C-Leu156C | 8.3 | 251 | 88 | 1.48 (1.15-1.90) | .002 |
HLA-B. -DRB1, -DQB1 -DPB1 locus had no significant substitutions. The impact of positions and types of amino acid substitution in HLA molecules was evaluated in pairs with HLA one-locus mismatch in HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 separately. For example, Tyr9A-Phe9A indicated amino acid substitutions of position 9 in HLA-A molecule at which donor had tyrosine and patient phenylalanine. The impacts of positions and kinds of amino acid substitutions in each HLA molecule were evaluated in pairs with HLA one locus mismatch in each HLA locus separately. Pairs which substituted specific amino acid at each position were compared with amino acid matched pairs at that position.
HS indicates hydropathy scale; HR, hazard ratio; CI, confidence interval; Tyr, tyrosine; Phe, phenylalanine; Asn, asparagine; Asp, asparatic acid; Ser, serine; Lys, lysine; Leu, leucine; and Arg, arginine.
Result of base analysis was significant but result of validating analysis using bootstrap resampling was not. Results of analysis were thus judged not to be statistically significant.
Measured in number of occurrences of severe acute GVHD.