Primary Immunodeficiency

Question 1

Immunodeficiency

Answer 1

Primary
Usually genetic

Acquired
Latrogenic

Question 2

Types of inheritance

Answer 2

Autosomal recessive - SCID variants
-To be affected, 2 mutated gene is needed (rr)
Autosomal dominant - Di George syndrome
-Mutation is dominant, hence only 1 mutated gene is needed
X-linked
-A recessive mutated gene carried on the X chromosome, usually labelled as Xr

Question 3

Primary immunodeficiencies - Classification

Answer 3

Any component of the immune system can go wrong.
Antibody deficiency
Complement
Phagocyte
combined
Combined with syndromic

Defects in innate immunity
Diseases of immune dysregulation
Autoinflammatory disorder
Phenocopies

Prevalence
1 : 500-1,200

Question 4

Antibody deficiency

Answer 4

X linked agammaglobulinaemia
-B lymphocyte precursors cannot mature
-Present at 6 months
-Absent tonsils
Common variable immunodeficiency
-IgG deficiency is core, low IgA and IgM
IgA deficiency
-1:500 affected
-Often asymptomatic
-IgA found on mucosal lining, respiratory/gut infections
-severe reaction to blood transfusion

Causes:
Recurrent ENT/airway infection
recurrent infection with encapsulated bacteria

Question 5

Phagocyte defects

Answer 5

Chronic granulomatous disease (CDG), usally X-linked

Defects in one of PHOX enzymes

Resulting in defects oxidative burst prevents oxidative killing

Affects neutrophils and macrophages

CDG treatment:
Antibiotic prophylaxis
Interferon
Haemotopoietic bone marrow transplant

Question 6

Complement deficiencies

Answer 6

C1 inhibitor deficient:
Autosomal dominant condition
Hereditary angio-oedemo (swelling in body)

Prophylaxis:
bradykinin receptor antagonist
recombinant C1-INH (inhibitor) replacement therapy

Emergency: fresh frozen plasma

C1-4 deficiency (recessive)
Leads to systemic lupus erythematosus (SLE)
Autoimmune disease affecting any parts of body
E.g renal disease, skin rash, joint pains

treatment: anti inflamminatories, supressants

C5-9 deficiencies
Autosomal recessive
Neisserial infection (gram negative diplococci)
Meningitis and gonorrhoea

Question 7

Properdin deficiency

Answer 7

X linked

Question 8

Combined immunodificiency

Answer 8

T cell absence or impairment
Affects humoral response immune system too, T helper cells required for B cell function
CD4 Ligand deficiency
-Hyper IgM syndrome
-B cells cannot switch from IgM to different class (G,A)
-Bacterial and opportunistic infection
-Usually X-linked

Severe combined immunodeficiency (SCID)
-Absence of functional T-lymphocyte, B lymphocyte may be involved
T-B+
X linked
IL-2RG decicient = cytokine y chain deficiency
Low T cells, non functional B cells

T-B-
Autosomal recessive
Adenosine deaminase deficiency

Intracellular pathogens; Mycobacterium,Salmonella,Virsuses, fungi, protozoa

SCID treatment:
HSCT
unaffected siblings
match unrelated donor
good result

Wiskott-Aldrich syndrome:
Combined immunodeficiency
Wiskott aldrich protein
T-cell and immunoglobulin dysfunction
-eczema
-lymphoma

Di-george syndome:
Autosomal dominant but 90-95% occur de novo
3 million base pair microdeletion at chromosome 22
Involved 45 genes
Branchial arch defects (part of embryo development) CATCH22
-C left palate
-A bnormal facies
-T hymic aplasia T cell deficient
-C ardiac

Treatment:
Multi-disciplinary team approach
Depends on clinical features
Surgical

Diagnosis is important
Death
Lung damage
Growth retardation
Deafness
No prophylaxis
No genetic councilling

Indicators of PIC:
Recurrent sire
Extensive candidiasis
Complication of live vaccine