Table 1.
Classification of Hyperinflammatory Syndromes.
| Disease | Gene | Protein | Defect | Trigger | Reference |
|---|---|---|---|---|---|
| Familial Hemophagocytic Lymphohistiocytosis | Infection | ||||
| FHL1 | 9q21-3-22 | Unknown | Unknown | (3) | |
| FHL2 | PRF1 | Perforin | Deficiency of cytotoxicity effector | (4) | |
| FHL3 | UNC13D | Munc13-4 | Impaired cytolytic vesicle maturation and release | (5) | |
| FHL4 | STX11 | Syntaxin 11 | Abnormal priming and release of cytolytic vesicles | (6) | |
| FHL5 | STXBP2 | Munc18-2 | Abnormal priming and release of cytolytic vesicles | (7) | |
| Immunodeficiency- Associated Hyperinflammatory | Infection | ||||
| Chédiak Higashi | LYST | LYST | Abnormal biogenesis of cytolytic vesicles | (8) | |
| Griscelli 2 | RAB27A | RAB27A | Abnormal cytolytic vesicle docking at the plasma membrane | (9) | |
| Hermansky-Pudlak 2 | AP3B1 | AP-3 | Impaired maturation and trafficking of cytotoxic granules | (10) | |
| XLP1 | SH2D1A | SAP | Defect in signaling pathway for cytotoxicity in T and NK cells | (11) | |
| XLP2 | XIAP | XIAP/Birc4 | Defect in apoptosis and immune effector signaling pathways | (12) | |
| ITK deficiency | ITK | ITK | Abnormal development, function, and/or survival of cytotoxic T cells | (13) | |
| Macrophage Activation Syndrome | Unknown | Unknown | Unknown | Rheumatic Disease Flare OR Infection | (14, 15) |
| Infection-Associated Hyperinflammatory Syndrome | Unknown | Unknown | Unknown | Infection | (14) |
| Malignancy-Associated Hyperinflammatory Syndrome | N/A | N/A | N/A | Malignancy | (14) |