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].

Bode et al. Arthritis Research & Therapy 2012 14:213   doi:10.1186/ar3843