Table 2.
HLA-mismatched haematopoietic stem cell transplantation (HSCT) pairs in study cohort 2 (N = 89 sibling pairs) analysed by genomic sequencing of the major histocompatibility complex (MHC) region.
| Pair id | Clinical HLA typing | NGS-HLA allele assignment of HLA-A,-B,-C,-DRB1,-DQA1, -DQB1 and -DPB1 genes | Determination of genomic 4.5 Mb sequence of the MHC region | Total match | GvHD grading | ||
|---|---|---|---|---|---|---|---|
| HLA-A,-B,-DRB1 match | Mismatched HLA allele | Mismatched HLA allele | HLA and non-HLA gene sequence mismatching | Acute | Chronic | ||
| 2468 | 5/6 | A | A | A, F, H, K | 30/34 | 1 | extensive |
| 5426 | 5/6 | B,C | B, C, DPB1 | B, C, MICA, TAP1, DPB1, DPB2 | 28/34 | 0 | no |
| 5624 | 5/6 | A | A | A, H, TAP2, TAP1, DMA | 29/34 | na | na |
| 5728 | 5/6 | A | A | A, F, H, K, L, E | 28/34 | 0 | limited |
| 5782 | 5/6 | A | A, DPB1 | A, F, H, K, DOB, TAP2, DPA1, DPB1 | 26/34 | na | na |
| 6245 | 5/6 | B,C | B, C | B, C, L, MICA, MICB | 29/34 | na | na |
| 6385 | 5/6 | A | A | A, G, H, K, TAP2 | 29/34 | na | na |
| 6768 | 5/6 | B,C | B, C | B, C, E, MICA, DOB, TAP2, TAP1 | 27/34 | 1 | extensive |
| 5672 | 6/6 | — | DPB1 | DPB1, DOB | 32/34 | na | na |
| 6907 | 6/6 | — | DPB1 | DPB1, DPA1 | 32/34 | na | na |
| 5559 | 6/6 | — | — | centromeric and telomeric to DPB2 | 34/34 | na | na |
| 7086 | 6/6 | — | — | telomeric to F | 34/34 | 0 | limited |
Eight pairs were known to have one allelic mismatch at HLA-A, -B or -DRB1 gene based on clinical HLA typing prior to HSCT. Allelic mismatching at HLA-DPB1 was revealed in two pairs by next generation sequencing allele assignment. Two more pairs were uncovered to be mismatched by genomic sequence comparison of the entire MHC segment. Only those genes with mismatching at the amino acid level are shown. + . HLA = human leukocyte antigen; MHC = major histocompatibility complex; MICA = MHC class I chain-related gene A; MICB = MHC class I chain-related gene B; TAP1 = transporter 1, ATP binding cassette subfamily B member; TAP2 = transporter 2, ATP binding cassette subfamily B member; GvHD = graft versus host disease.