Immunodeficiency disorders

Question 1

antibody production defects presentation

Answer 1

sinopulmonary infections, including pneumococcus, haemophilus, mycoplasma
GI infections
Meningitis/sepsis

Question 2

X-linked Ammunoglobulinemia (XLA)

Answer 2

antibody production defect

X-linked, mostly boys, though de novo mut possible

Block BTK gene –>no B cell development –> no antibodies

protective maternal antibodies serve protection for first 1-2 months of life

Question 3

Common Variable immunodeficiency

Answer 3

antibody production defect
most common primary symptomatic immunodeficiency
Reduced IgG, A, M
reduced or absent antibody production
increased mortality and morbidity due to autoimmune/inflammatory complications
25-50% have genetic muts

Question 4

X-linked Hyper IgM syndrome

Answer 4

Boys only
Normal-high IgM, low IgA,G,E
CD40LG gene afects antibody class-switching
AR forms exist

Question 5

Selective IgA deficiency

Answer 5

most asymptomatic
very common, most have no symptoms
Increased risk of autoimminity, GI and respiratory illness

Question 6

antibody production defects treatment

Answer 6

Immunoglobin (antibody) replacement therapy
Antibiotics Prophylaxis
Immune suppressants or immune modulator
Future: targeted therapy for gene defects

Question 7

Cellular/combined defects presentation

Answer 7

facial dysmorphia, ectodermal dysplasia
FTT
opportunistic infections
skin changes, rash
adverse effects to live vaccines

Question 8

SCID

Answer 8

Cellular/combined defects
Fatal in first 2 years if not treated
X-linked (most common) or AR
affects development of T-cells, which orchestrate immune response

Question 9

SCID treatment

Answer 9

avoid live vaccine
avoid breast feeding
bone marrow transplant
ERT
gene therapy - lentiviral vector trials

screening: TREC

Question 10

Wiskott-Aldrich syndrome

Answer 10

Cellular/combined defects

Immune deficiency: bacteria, virus, fungal

SYMPTOMS:
skin rash, eczema
small platelets, easy bruising

Genetics: X-linked

Treatment: cell transplant highly effective

Question 11

Chronic granulomatous defects

Answer 11

Phagocyte immune defect

muts in genes that make up NADPH oxidase –> no superoxide produced –> infections and inflammation

Question 12

Chronic granulomatous defects: testing and treatment

Answer 12

TESTING: DHR to detect how much of cell is making ROS

TREATMENT:

• antibiotics prophylaxis
• antifungal prophylaxis
• no vaccines
• transplant is curative!

Question 13

Chediak-Higashi syndrome

Answer 13

Phagocyte Immune Defect

AR: LYST gene defect, impairs lysosomal functioning
infections
albinism
risk for HLH Hemophagocytic lymphohistiocytosis

Question 14

Complements defects

Answer 14

Susceptible to encapsulated bacteria
C2 deficiency is the most common in Caucasian
Need vaccines: meningococcus, pneumococcus, haemophilus vaccines