Primary Immuno Deficiencies

Question 1

Agammaglobulinemia (X-linked & autosomal recessive)

Answer 1

Brutons - defect in B cell tyrosine kinase (BTK)
Defects in B cell development - failure to mature
Germinal center formation defective, underdevelopment of lymphoid tissues: lymph nodes, Peyer’es patches, spleen, tonsils, adenoids
85% X linked
IgG usually <100 mg/dl
B cells <2% of lymphocytes (usually 0.05-.3%)
Normal T cell number and function

Question 2

Hyper-IgM Syndromes

Answer 2

Most commonly due to defect of CD40L on Th cells
Class switching defects
Normal # B cells
Increased IgM (or normal)
Low IgG, IgE, IgA

Question 3

IgA Deficiency

Answer 3

Most common primary immunodeficiency
IgA <5-7 mg/dl
usually asymptomatic (but does airway, diarrhea, autoimmune, sinopulmonary infections)

Question 4

Common Variable Immunodeficiency

Answer 4

Second most common PID after IgA deficiency (MOST SYMPTOMATIC)
Most prevalent PID in adults (presens after 2, can be very delayed)
sinusitis, pneumonia
Reduced IgG, IgA and/or IgM
Absent or imparied specific antibody responses to previous antigens
Causes of CVID unknown

Question 5

Specific Antibody Deficiency

Answer 5

Recurrent sinopulonary infections
Normal IgG, IgA, IgM
Normal B and T cell number and function
Impaired vaccine response (polysaccharide)
Imparied antibody response to natural infection with encapsulated bacteria

Question 6

Transient Hypogammaglobulinemia of Infancy

Answer 6

Recurrent sinopulmonary infections
Low IgG, but normal specific antiboides
Normal lymphocye number and function˚
Delay in maturation of T cell help for antibody production?
Onset ~6 months of age, resolved by age 4

Question 7

Omenn Syndrome (severe combined immunodeficiency)

Answer 7

Hypomorphic mutations, most commonly in RAG genes
Low to normal T cells (but oligoclonal T cell population)
Early onset (<3 months) of a diffuse, exudative erythroderma
lymphadenopathy, chronic persistent diarrhea, failure ot thrive
Elevated IgE and Eosinophilia
Considered “leaky” SCID

Question 8

DiGeorge Syndrome

Answer 8

Defect in embryogenesis, 3rd and 4th pharyngeal pouches
Most have deletion of 22q11.2
Dysmorphic faces, hypocalcemia (absent parathyroid), depressed T-cell immunity (hypoplastic to aplastic thymus), congenital heart disease
presents in first few days of life (tetany)
diagnosed immediately by later chest x-ray (absence of thymic shadow)
partial vs complete

Question 9

Wiskott Aldrich Syndrome

Answer 9

Patients with: Eczema, Thrombocytopenia with small platelets (look for low MPV-mean platelet volum), immunodeficiency
Wiskott Aldrich Syndrome Protein (WASP) is involved with actin polymerization - thought to affect lymphocyte function
X-linked recessive

Question 10

Chronic Granulomatous Disease

Answer 10

Recurrent bacterial infection with catalase positive organisms (staph, serratia; also aspergillus)
Defect of NADPH oxidase decreases reactive oxygen species and repiratory burst in neutrophils
diagnosed by Nitroblue tetrazolium dye test; superoxide radical formation - chemiluminescence test), flow cytometry - dihydrorhodamine 123 assay
X-linked recessive most common

Question 11

Leukocyte Adhesion Deficiency

Answer 11

Defect in LFA-1 integrin (CD18) protein on phagocytes; imparied migration and chemotaxis; autosomal recessive
Recurrent soft tissue infections, delayed umblical cord seperation, no pus formation, high neutrophils but absent at infection site

Question 12

Hyper IgE Syndrome

Answer 12

Deficiency of Th17 cells due to STAT3 mutation
high IgE and eosinophils
recurrent staphylococcal absecesses, sinopulmonary infections, severe eczema; retained primary teeth; recurrent candida; recurrent bone fractures