Table 2.
Heterozygous variants in 15 of 29 patients with acquired HLH
| Patient | Age, y | Disease | Genes (n of variants)* | NK cell functions | ||
|---|---|---|---|---|---|---|
| Perforin expression | Degranulation | Direct cytotoxicity | ||||
| 1 | 71 | Lymphoma | LYST† (×1), UNC13D (×2) | N | N | N |
| 2 | 76 | Idiopathic | PRF1† (×1), UNC13D (×1), LYST (×1) | N | N | N |
| 3 | 32 | Bacterial infection | LYST (×7) | N | N | — |
| 4 | 85 | Idiopathic | PRF1 (×1) | N | N | N |
| 5 | 70 | Idiopathic | LYST† (×1) | ↓ | — | — |
| 6 | 78 | Bacterial infection | STX11 (×1) | N | N | N |
| 7 | 87 | Lymphoma | LYST† (×1) | N | N | N |
| 8 | 58 | Parasitic infection | LYST (×1) | N | N | N |
| 9 | 63 | Parasitic infection | PRF1 (×1) | N | N | N |
| 10 | 33 | SLE | UNC13D (×1) | N | ↓ | — |
| 11 | 91 | Idiopathic | PRF1 (×1) | ↓ | ↓ | ↓ |
| 12 | 70 | Idiopathic | PRF1 (×1), UNC13D (×1), LYST† (×1) | N | N | N |
| 13 | 60 | Idiopathic | UNC13D (×1) | — | — | — |
| 14 | 61 | Bacterial infection | UNC13D† (×1) | N | N | N |
| 15 | 63 | Lymphoma | PRF1† (×1), UNC13D (×1) | N | N | — |
—, not done; N, normal; SLE, systemic lupus erythematosus.
*
PRF1, perforin gene (biallelic mutation = FHL2); UNC13D, MUNC13-4 gene (biallelic mutation = FHL3); STX11, syntaxin 11 gene (biallelic mutation = FHL5); LYST (biallelic mutation = Chediak-Higashi syndrome); no heterozygous mutations with the selective criteria were found for STXBP2, SH2D1A, RAB27A, XIAP, or ITK genes.
†
Variant known as pathogenic.