Inborn Errors of Immunity

Types of B cells

CD19+, CD20+

Types of T Cells

CD3+, CD4+, CD8+

Types of Phagocytes

macrophages, neutrophils

B cell deficiencies

sinus, ear, lung infections w/ encapsulated bacteria

T-cell deficiencies

severe viral infections

severe fungal infectons

opportunistic infections

chronic infections diarrhea

Phagocyte Deficiencies

fungal and bacterial infection

skin abcesses

lymphoadenitis

osteomyelitis

NK cell deficiency

herpes simplex, CMV, EBV

increased malignancies

HLH

MHC issues

Class II: bacterial, fungal, viral, FTT

Class I: ulcerative skin lesions, bacterial infections

Cytokine issues

inflammatory disease

Complement issues

sinus, ear, lung w/ encapsulated bacteria

early onset autoimmune

recurrent meningitis

X-Linked Severe Combined Immunodeficiency Syndrome (SCID)

IL2RG gene

T-, B+, NK-

X-Linked Agammaglobulinema gene

BTK

Agammaglobulinemia symptoms

recurrent ear infections, pneumonitis, sinusitis, conjunctivitis <5yr

life-threatening bacterial infections: sepsis, cellulitis

T+, B- or low, NK+

Hemophagocytotic Lymphocytosis symptoms

fever, splenomegaly, cytopenia, hypertrigliceridemia, hemophagocytosis

Low/ absent NK

HLH genetics

PRF1 (30-40%)

UNC13D (20-40%)

STX11 (5-25%)

STXBP2 (5-25%)

Chronic Granulomatous Disease (CGD)

severe recurrent bacterial/fungal infections

lung, lymph node, liver, bone, skin

chronic colitis

granuloma formation

pathogens: Staph. a., Burkholderia, Serratia

Chronic Granulomatous Disease gene

CYBB (X-linked)

CYBA, CYBC1, NFC1, NFC2, NFC4

CGD Carriers

mild symptoms; autoimmune (lupus, IBD), photosensitivity, polyarthritis, oral ulcers, alopecia, Raynaud’s

STAT1 Gain of Function

Chronic mucocutaneous candidiasis (CMC), fungal, bacterial, viral infections

Autoimmune, hypothyroidism, T1DM, cytopenia, Lupus

Delayed pubery, osteoporosis, asthma, eczema, possible increase cancer risk, cardiac/vascular, intercranial aneurysms

Familial Mediterranian Fever

periodic episodes of inflammation, fever, rash, muscle aches, pain in chest, abdomen, joints

childhood/teenage onset

uncontrolled can lead to amyloidossi in kidney

FMF gene

MEFV - AR w/ reduced penetrance

Immunodeficiencies

SCID, CIDs

Wiscott-Aldrich, Ataxia Telangectasia, Nimegen breakage, NEMO, AD-HIES, Loeys-Dietz, 22q11.2

Antibody Deficiencies

XL Agammaglobulinemia

Immune Dysregulation

HLH, diseases associated w/ EBV susceptibility, ALPs

Phagocytotic Disorders

Schwann-Diamond, LAD, Elastase deficiencies, CGD

Disorders of Innate Immunity

STAT1 deficiency (AR), STAT1 GOF (AD), MSMD (AR severe STAT1 def)

Autoinflammatory Disorders

FMF, Accardi-Goutieres