Clinical and genetic characteristics of 27 HA subjects whose T-cell responses were analyzed
| HA subject . | Age (y) . | Race* . | HA severity . | Recent titer, peak titer† . | ITI? . | FVIII mutation, HGVS‡ . | FVIII mutation, legacy§ . | DRB1 alleles . | FVIII variant analyzed . |
|---|---|---|---|---|---|---|---|---|---|
| 001-043 | 18+ | AA | Mild | Never | No | ND | ND | 0301, 0701|| | V2238 |
| 002-033 | 4-17 | AA | Severe | 0 (1 y ago), 17 (11 y ago) | Yes | ND | ND | 1503, 1503 | V2238 |
| 009-035 | 18+ | AA | Severe | Never | No | Int22 | Int22 | 0804, 1101g¶ | V2238 |
| 016-005 | 18+ | AA | Severe | 0 (2 y ago), 14 (16 y ago) | No | ND | ND | 0101, 1301 | V2238 |
| 004-022 | 4-17 | AA | Severe | Never | No | Int22 | Int22 | 1201g, 1302 | V2238 |
| 009-034 | 18+ | AA | Severe | 0 (2 y ago), 9 (17 y ago) | Yes | Int22 | Int22 | 0804, 1302 | V2238 |
| 011-052 | 2-3 | AA | Severe | Never | No | ND | ND | 0901, 1102 | V2238 |
| 015-006 | 4-17 | AA | Severe | 0 (2 y ago), 1.3 (6 y ago) | No | Int22 | Int22 | 1202, 1302 | V2238 |
| 002-017 | 4-17 | AA | Severe | Never | No | c.791T>C, p.Leu264Pro | CTG→CCG, L245P | 1101, 1201g | V2238 |
| 004-020 | 4-17 | AA | Severe | 0 (2 y ago), 32 (6 y ago) | Yes | Int1 | Int1 | 0301, 0804 | V2238 |
| 016-027 | 4-17 | AA | Severe | 0 (2 y ago), 6 (13 y ago) | No | ND | ND | 0301, 1401 | V2238 |
| 004-005 | 18+ | W | Severe | Never | No | ND | ND | 0701, 0804 | V2238 |
| 004-013 | 4-17 | AA | Severe | Never | No | Int1 | Int1 | 1201g, 1501 | V2238 |
| 007-002 | 18+ | AA | Severe | Never | No | ND | ND | 0101, 0804 | V2238 |
| 011-001 | 4-17 | AA | Severe | 15 (2 wk ago), 309 (no date) | Yes | Int22 | Int22 | 1101, 0701 | V2238 |
| 002-025 | 2-3 | AA | Severe | 0 (same day), <0.5 (1 y ago) | Yes | c.3637del, Ile1213Phefs*5 | ΔA, E1191-I1194 | 0301, 0804 | V2238 |
| 005-019 | 18+ | SEA | Severe | 1.0 (4 mo ago), 132 (no date) | Yes | Int22 | Int22 | 1101, 0301 | M2238 |
| 013-011 | 18+ | W | Severe | Never | No | c.3637dup, p.Ile1213Asnfs*28 | +A, E1191-I1194 | 1101, 0103 | M2238 |
| 013-013 | 4-17 | AA | Severe | Never | No | c.1171C>T, p.Arg3191Cys | CGC→TGC, R372C | 0301, 1401g | M2238 |
| 014-016 | 4-17 | AA | Severe | 0.3 (5 mo ago), 34 (no date) | Yes | c.5961dup, p.Glu1988Argfs*4 | GAG→AGAG, E1969 | 0301, 0301 | M2238 |
| 008-006 | 2-3 | AA | Severe | 13 (same day), 87 (5 wk later) | No | c.6967C>T, p.Arg2323Cys | CGC→TGC, R2304C | 0301, 1301 | M2238 |
| 011-016 | 18+ | AA | Severe | 0 (2 y ago), 11 (20 y ago) | Yes | ND | ND | 0701, 1302 | H484 |
| 013-024 | 4-17 | AA | Severe | 0 (1 y ago), 1126 (∼10 y ago) | Yes | Int22 | Int22 | 0701, 1001 | D1241 |
| 009-003 | 2-3 | W | Severe | 0 | No | ND | ND | 0404, 0901 | D1241 |
| 011-020 | 18+ | W | Severe | 0 | No | ND | ND | 0701, 0901 | D1241 |
| 005-015 | 18+ | W | Mild | 2-7 (4 y ago), 250 (7 y ago) | No | A2201P (from chart) | 0101, 1503 | D1241 | |
| 007-029 | 18+ | W | Severe | 0 (2 y ago), 280 (21 y ago) | Yes | ND | ND | 0101, 0701 | D1241 |
| HA subject . | Age (y) . | Race* . | HA severity . | Recent titer, peak titer† . | ITI? . | FVIII mutation, HGVS‡ . | FVIII mutation, legacy§ . | DRB1 alleles . | FVIII variant analyzed . |
|---|---|---|---|---|---|---|---|---|---|
| 001-043 | 18+ | AA | Mild | Never | No | ND | ND | 0301, 0701|| | V2238 |
| 002-033 | 4-17 | AA | Severe | 0 (1 y ago), 17 (11 y ago) | Yes | ND | ND | 1503, 1503 | V2238 |
| 009-035 | 18+ | AA | Severe | Never | No | Int22 | Int22 | 0804, 1101g¶ | V2238 |
| 016-005 | 18+ | AA | Severe | 0 (2 y ago), 14 (16 y ago) | No | ND | ND | 0101, 1301 | V2238 |
| 004-022 | 4-17 | AA | Severe | Never | No | Int22 | Int22 | 1201g, 1302 | V2238 |
| 009-034 | 18+ | AA | Severe | 0 (2 y ago), 9 (17 y ago) | Yes | Int22 | Int22 | 0804, 1302 | V2238 |
| 011-052 | 2-3 | AA | Severe | Never | No | ND | ND | 0901, 1102 | V2238 |
| 015-006 | 4-17 | AA | Severe | 0 (2 y ago), 1.3 (6 y ago) | No | Int22 | Int22 | 1202, 1302 | V2238 |
| 002-017 | 4-17 | AA | Severe | Never | No | c.791T>C, p.Leu264Pro | CTG→CCG, L245P | 1101, 1201g | V2238 |
| 004-020 | 4-17 | AA | Severe | 0 (2 y ago), 32 (6 y ago) | Yes | Int1 | Int1 | 0301, 0804 | V2238 |
| 016-027 | 4-17 | AA | Severe | 0 (2 y ago), 6 (13 y ago) | No | ND | ND | 0301, 1401 | V2238 |
| 004-005 | 18+ | W | Severe | Never | No | ND | ND | 0701, 0804 | V2238 |
| 004-013 | 4-17 | AA | Severe | Never | No | Int1 | Int1 | 1201g, 1501 | V2238 |
| 007-002 | 18+ | AA | Severe | Never | No | ND | ND | 0101, 0804 | V2238 |
| 011-001 | 4-17 | AA | Severe | 15 (2 wk ago), 309 (no date) | Yes | Int22 | Int22 | 1101, 0701 | V2238 |
| 002-025 | 2-3 | AA | Severe | 0 (same day), <0.5 (1 y ago) | Yes | c.3637del, Ile1213Phefs*5 | ΔA, E1191-I1194 | 0301, 0804 | V2238 |
| 005-019 | 18+ | SEA | Severe | 1.0 (4 mo ago), 132 (no date) | Yes | Int22 | Int22 | 1101, 0301 | M2238 |
| 013-011 | 18+ | W | Severe | Never | No | c.3637dup, p.Ile1213Asnfs*28 | +A, E1191-I1194 | 1101, 0103 | M2238 |
| 013-013 | 4-17 | AA | Severe | Never | No | c.1171C>T, p.Arg3191Cys | CGC→TGC, R372C | 0301, 1401g | M2238 |
| 014-016 | 4-17 | AA | Severe | 0.3 (5 mo ago), 34 (no date) | Yes | c.5961dup, p.Glu1988Argfs*4 | GAG→AGAG, E1969 | 0301, 0301 | M2238 |
| 008-006 | 2-3 | AA | Severe | 13 (same day), 87 (5 wk later) | No | c.6967C>T, p.Arg2323Cys | CGC→TGC, R2304C | 0301, 1301 | M2238 |
| 011-016 | 18+ | AA | Severe | 0 (2 y ago), 11 (20 y ago) | Yes | ND | ND | 0701, 1302 | H484 |
| 013-024 | 4-17 | AA | Severe | 0 (1 y ago), 1126 (∼10 y ago) | Yes | Int22 | Int22 | 0701, 1001 | D1241 |
| 009-003 | 2-3 | W | Severe | 0 | No | ND | ND | 0404, 0901 | D1241 |
| 011-020 | 18+ | W | Severe | 0 | No | ND | ND | 0701, 0901 | D1241 |
| 005-015 | 18+ | W | Mild | 2-7 (4 y ago), 250 (7 y ago) | No | A2201P (from chart) | 0101, 1503 | D1241 | |
| 007-029 | 18+ | W | Severe | 0 (2 y ago), 280 (21 y ago) | Yes | ND | ND | 0101, 0701 | D1241 |
AA, African American; SEA, SE Asian; W, white.
Inhibitor titers in BU/mL were not available for all subjects on the day of sample collection, therefore the most recently determined titers are reported.
HGVS: Human Genome Variation Society nomenclature, in which residue 1 is the first residue of the signal peptide. Int1, intron-1 inversion; Int22, intron-22 inversion; ND, not determined.
Legacy nomenclature, in which residue 1 is the first residue of the FVIII protein after signal peptide removal.
HLA-DRB1 identifiers in bold indicate that the corresponding HLA-DRB1 tetramers were used to analyze CD4 T-cell responses for these subjects. Cells from mild HA subject 001-043 were analyzed because his F8 gene encoded FVIII-V2238. Cells from mild HA subject 005-015 were analyzed because he had a recently resolved inhibitor. Five of 15 subjects with an inhibitor history did not receive ITI. One of these (008-006) had his inhibitor diagnosed at enrollment and 1 (005-015) had received FVIII only to support surgery.
Alleles with the suffix “g” are the most likely of multiple alternative genotypes encoding identical protein sequences in the HLA-DRB1 antigen recognition site.