Primary immunodeficiency disorders

Primary immunodeficiency disorders may be classified according to which component of the immune system they affect.

Complement deficiency

Hereditary angioedema due to C1 inhibitor deficiency
SLE-like syndromes due to deficiencies of classical pathway components
PNH due to regulator protein defects
Impaired response to encapsulated organisms (eg Pneumococci) with C3 deficiency
Impaired response to Neisseria infection with deficiency of terminal complement components (C5-C9)

Disorder with Macrophage activation

Inherited defects (usually autosomal recessive) involving the IFN-gamma signaling pathway result in disseminated mycobacterial disease in infancy or early childhood. Patients require lifelong treatment with antimycobacterial agents.

Bare Lymphocyte Syndrome

An immunodeficiency resulting from a defect in expression of HLA class II antigens on the surfaces of antigen presenting cells.

Neutrophil disorders

Disorder	Underlying defect	Notes
Chronic granulomatous disease	Lack of NADPH oxidase (X-linked defect) reduces ability of phagocytes to produce reactive oxygen species;Dx by DHR flow cytometry;can do NBT testing also	Causes recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (e.g. Staphylococcus aureus and fungi (e.g. Aspergillus)
Chediak-Higashi syndrome	autosomal recessive; mutation of a lysosomal trafficking regulator protein; Microtubule polymerization defect >> neutrophil phagosome lysosome fusion; lysosomes lack elastase and cathepsin G;Dx - Dohle bodies (ruptured rough endoplasmic reticulum) and bone marrow smears which show "giant inclusion bodies" in leucocyte precursor cells	Affected children have 'partial albinism' and peripheral neuropathy; (horizontal) nystagmus; Neutropenia >>recurrent bacterial infections (usually S. aureus); deciduous dentition and periodontal disease; eventually reach an accelerated phase, aka lymphoma-like-syndrome (which may link to EBV infection) Tx: Prevent infections with daily Bactrim and daily ascorbic acid
Leukocyte adhesion deficiency	Defect of LFA-1 integrin (CD18) protein on neutrophils; biopsy of infected tissue shows inflammatory infiltrate devoid of neutrophils	Recurrent bacterial infections. Delay in umbilical cord sloughing may be seen; no pus formation at sites of infection; poor wound healing

Nitroblue Tetrazolium (NBT) testing

When NBT is added, properly function neutrophils that can produce reactive oxygen species turn yellow NBT to dark blue formazan, (seen as precipitates within cells)

Dihydrorhodamine (DHR) flow cytometry

assesses the production of superoxide radicals by measuring the conversion of DHR to rhodamine, a fluorescent green compound that can be detected by flow cytometry machines.

Sample with deficient NADPH oxidase will exhibit decreased fluorescence.

Leukocyte adhesion deficiency (LAD)