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

Ch├ędiak 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