Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis

Table 1 Classification of hemophagocytic lymphohistiocytosis

	Gene	Protein	Function
Genetic defects ('primary')
FHL1	Unknown (location 9q21.3-22)
FHL2	PFR1	Perforin	Pore-forming protein
FHL3	UNC13D	Munc13-4	Vesicle priming
FHL4	STX11	Syntaxin-11	Vesicle transport and fusion
FHL5	STXBP2	Munc18-2	Interacts with syntaxin-11 for vesicle transport and fusion
Immunodeficiency syndromes associated with albinism
Chédiak Higashi syndrome	LYST	LYST	Probably important for size and function of lytic granules
Griscelli syndrome type II	Rab27A	Rab27A	Vesicle docking/granule movement
Hermansky-Pudlak syndrome type II	AP3B1		Vesicle biogenesis, protein sorting
Other primary immunodeficiencies
X-linked lymphoproliferative disorder type I	SH2D1A	SAP	Signal transduction and activation of lymphocytes
X-linked lymphoproliferative disorder type II	BIRC4	XIAP	Inhibition of apoptosis
ITK deficiency	ITK	ITK	T-cell kinase
Other diseases associated with HLH ('secondary')	Examples
Infections	EBV, leishmania
Macrophage activation syndrome	Still's disease, SLE
Autoinflammatory
Malignancy	T cell lymphoma
Immunosuppression	Post organ
	transplantation
Metabolic disease	Lysinuric protein
	intolerance
Post-HSCT

EBV, Epstein-Barr virus; FHL, familial hemophagocytic lymphohistiocytosis; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoetic stem cell transplantation; ITK, IL-2 inducible T-cell kinase; SLE, systemic lupus erythematosus. Adapted from [1, 20, 49, 87].

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