Immune deficiencies

Question 1

X-linked (Bruton) agammaglonulinemia

Answer 1

X-linked recessive B-cell disorder caused by defect in BTK (tyrosine kinase gene), leading to no B cell maturation, no Ig’s.

Recurrent bacterial and enteroviral infections after 6 months (after decline in maternal IgG), especially enterovirus (e.g. polio and coxsackievirus) and Giardia lamblia

Normal CD19+ B cell count, decreased pro-B, decreased Ig of all classes. Absent/scanty LNs and tonsils

Question 2

Selective IgA deficiency

Answer 2

B-cell disorder; most common primary immunodeficiency.

Majority of cases are asymptomatic. Symptoms include Airway and GI infections, Autoimmune disease, Atopy, Anaphylaxis to IgA-containing products.

Decreased IgA, Normal IgG, IgM.

Question 3

Common Variable Immunodeficiency

Answer 3

B-cell disorder caused by defect in B-cell differentiation. Can be acquired in 20s-30s.

Increased risk of autoimmune diseases, bronchiectasis, lymphoma, and sinopulmonary infections

Decreased plasma cells and decreased immunoglobulins

Question 4

Thymic aplasia (DiGeorge syndrome)

Answer 4

T-cell disorder caused by 22q11 deletion, leading to failure to develop 3rd and 4th pharyngeal pouches (absent thymus and parathyroids).

Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), conotruncal abnormalities (tetralogy of Fallot, truncus arteriosus)

22q11 deletion detected by FISH

Question 5

IL-12 receptor deficiency

Answer 5

Autosomal recessive T-cell disorder, resulting in decreased Th1 cells.

Results in disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.

Decreased IFN-gamma (produced by Th1 cells)

Question 6

Autosomal dominant hyper-IgE syndrome (Job syndrome)

Answer 6

Autosomal domainnt T-cell disorder caused a deficiency in Th17 cells (STAT3 mutation), leading to impaired recruitment of neutrophils to sites of infection.

“FATED”: coarse Facies, noninflamed staph Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema)

Increased IgE, decreased IFN-gamma

Question 7

Chronic mucocutaneous candidiasis

Answer 7

T-cell disorder resulting in noninvasive Candida infections of skin and mucous membranes.

Absent cutaneous reaction to Candida antigens

Question 8

Severe combined immunodeficiency (SCID)

Answer 8

Combined B- and T-cell disorder with several types:

1. IL-2R gamma chain (most common, X-linked)
2. Adenosine deaminase deficiency (AR) - build-up of adenosine and deoxyadenosine is toxic to lymphocytes
3. MHC class II deficiency

Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections.

Tx: Bone marrow transplant (no concern for rejection)

Question 9

Ataxia-telangiectasia

Answer 9

Autosomal recessive combined B- and T-cell disorder causd by defective ATM gene (DNA repair gene), leading to hypersensitivity to ionizing radiation.

Ataxia (cerebellar atrophy), oculocutaneous telangiectasias, repeated sinopulmonary infections, and increased incidence of malignancy.

Increased AFP. Decreased IgA, IgG, IgE. Lymphopenia.

Question 10

Hyper-IgM syndrome

Answer 10

X-linked combined B- and T-cell disorder caused by defect CD40L on Th cells, resulting defective class switching.

Severe pyogenic infections (due to poor opsonization) at mucosal sites and opportunistic infections (Pneumocystis, Cryptosporidium, CMV)

Increased IgM. Decreased IgG, IgA, IgE.

Question 11

Wiskott-Aldrich syndrome

Answer 11

X-linked combined B- and T-cell disorder caused by mutation in WAS gene, resulting in an inability of T cells to reorganize actin cytoskeleton.

“WATER”: Wiskott-Aldrich, Thrombocytopenic purpura, Eczema, Recurrent infections.

Increased risk of autoimmune disease and malignancy.

Increased IgE and IgA. Decreased to normal IgG and IgM. Fewer and smaller platelets.

Question 12

Leukocyte adhesion deficiency (type 1)

Answer 12

Autosomal recessive phagocyte dysfunction caused by defect in LFA-1 integrin (CD18) protein on phagocytes, leading to impaired migration and chemotaxis.

Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, and delayed separation of the umbilical cord.

Increased number of neutrophils, but absence of neutrophils at the infection site.

Question 13

Chediak-Higashi syndrome

Answer 13

Autosomal recessive phagocyte dysfunction caused by defect in lysosomal trafficking regulator gene (LYST), resulting in microtubule dysfunction in phagosome/lysosome fusion.

Recurrent pyogenic infections by staph and strept, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.

Giant granules in neutrophils and platelets. Pancytopenia. Mild coagulation defects.

Question 14

Chronic granulomatous disease

Answer 14

X-linked recessive phagocyte dysfunction caused by NADPH oxidase defect, leading to decreased ROS and absent respiratory burst in neutrophils.

Increase susceptability to catalase-positive organisms (PLACESS): Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia marcescens; also Nocardia

Abnormal dihydrorhodamine (flow cytometry) test.

Nitroblue tetrazolium dye reduction test is negative

Question 15

Catalase positive organisms

Answer 15

“PLACESS”:

Pseudomonas

Listeria

Aspergillus

Candida

E. coli

S. aureus

Serratia

Also, Nocardia

Question 16

Myeloperoxidase (MPO) deficiency

Answer 16

Phagocyte dysfunction caused by deficiency in MP and decreased conversion of H2O2 to HOCl

Increased risk for Candida infections, but most patients are asymptomatic.

Nitroblue tetrazolium test is normal because the respiratory burst is intact.