Primary Immunodeficiency

Question 1

Neutrophil disorder

Answer 1

Chronic granulomatomous disease
Chediak-higashi syndrome
Leukocyte adhesion deficiency

Question 2

B-cell disorders

Answer 2

IgAdeficiency
Bruton’s congential agammaglobinemia
Common variable immunodeficiency

Question 3

T cell disorders

Answer 3

DiGeorge

• microdeletion
• increased risk or viral and fungal infections

Question 4

Combined B and T cell disorders

Answer 4

Severe combined immunodeficiency 
Ataxic telangectasia (autosomal recessive, 10% risk of malignancy, lymphoma or leukaemia and non-lymphoid tumours, recurrent chest infections)
Wisconsin-Aldrich (X linked recessive) WASP gene mutation, recurrent bacterial infections, eczema and thrombocytopenia with low IgG

Question 5

Chronic granulomatous disease

Answer 5

Neutrophil disorder
Lack of NADPH oxidase reduces ability of phagocytes to produce ROS
Recurrent pneumonia’s and abscesses particularly due to catalase positive bacteria (eg staph aureus) and fungi
- negative nitroblue-tetrazolium test
- abnormal dihyrorhidamine flow cytometry test

Question 6

Chediak- Higashi syndrome

Answer 6

Neutrophil disorder
Microtubule polymerisation defect -> reduction in phagocytosis

‘Partial albinism’ and peripheral neuropathy
Recurrent bacterial infections

Giant granules in neutrophils and platelets

Question 7

Leukocyte adhesion deficiency

Answer 7

Neutrophil disorder
Defect of LFA-1 (CD18) integrin on neutrophils

Recurrent bacterial infections
Delay in umbilical cord sloughing
Absence of neutrophils/pus at sites of infection

Question 8

Common variable immunodeficiency

Answer 8

B cell disorders

Varying causes

Hypogammaglobulinemia is seen
May predispose to autoimmune disorders and lymphoma

Question 9

Bruton’s (x-linked) congential deficiency

Answer 9

Defect in Bruton’s tyrosine kinase (btk) gene that leads to a severe block in B cell development

X linked recessive
Recurrent bacterial infections
Absence of B cells with reduced immunoglobulins of all classes

Question 10

Selective immunoglobulin A deficiency

Answer 10

Maturation defect in B cells
Most common primary antibody deficiency
Recurrent sinus and resp infections
Associated: coeliac disease and may cause false negative coeliac Ab screen

Severe reactions to blood transfusions may occur- anti IgA abs-> anaphylaxis

Question 11

DiGeorge syndrome

Answer 11

T cell disorder
22q11.2 deletion

Failure to develop 3rd and 4th pharyngeal pouches

Commonly: CHD, learning difficulties, hypocalcemia, recurrent viral/fungal infections, cleft palate

Question 12

Severe combined immunodeficiency

Answer 12

Many causes
Commonly X linked due to defect in common gamma chain, a protein used in receptor for IL-2 and other interleukins.
Recurrent infections

Reduced T cell receptor excision circles
Stem cell transplant may be useful

Question 13

Ataxic telangectasia

Answer 13

Combined B and T cell disorder
Defect in DNA repair enzymes

Autosomal recessive

Features: cerebellar ataxia, telangectasia, recurrent chest infections, 10% risk of malignancy (lymphoma, leukaemia)

Question 14

Wiskott-Aldrich syndrome

Answer 14

Combined B and T disorder

Defect in WASP gene

X liked recessive

Recurrent bacterial infections, eczema, thrombocytopenia.
Low IgM levels

Increased risk AI and malignancy