Laboratory Diagnostic Investigations (III) - Immunological disorders

Question 1

Consequence of primary immunodeficiency disease

Answer 1

Primary immunodeficiency disease

Genetic predis. to recurrent infections, malignancies, allergies, auto-immune diseases

Question 2

Examples of Phenocopies of Primary immunodeficiency disease

Answer 2

Autoimmune lymphoproliferative syndrome (ALPS)

• Autoantibodies against immune cytokines

Question 3

Main type of mutation that causes inborn immunodeficiency diseases?
Treatment?

Answer 3

Mostly single gene disorder
Many are treatable
- e.g. HSC transplant for Severe combined immunodeficiency

Question 4

2 approaches to screen for immunodeficiency diseases

Answer 4

1) Phenotype approach: Sanger sequencing of specific gene

2) Targeted HGS: Screen large panels of candidate genes

Question 5

Most common type of primary immunodeficiency disease

Answer 5

Common variable immunodeficiency disorder (CVID)

Question 6

Clinical Presentation of Common variable immunodeficiency disorder (CVID)

Answer 6

• Hypo-gamma-globinaemia (late onset)
• Respiratory tract infection with bronchiectasis (recurrent)
• Diarrhea (intermittent or chronic)
• Polyclonal lymphoproliferation with splenomegaly
• Autoimmune hemolytic anemia
• GI and lymphoid cancers

Question 7

genetic cause of CVID

Answer 7

4 known mutations

ICOS
CD19
BAFF-R
TACI

Question 8

Name of diagnostic criteria for CVID

Answer 8

ESID diagnostic criteria

Question 9

Clinical use of molecular testing for Primary immunodeficiency disease

Answer 9

1. Diff. genetic cause from acquired cause (e.g. viral infection and drugs)
2. Confirm clinical diagnosis
3. Screen for at-risk relatives
4. Identify novel or atypical presentation of PID

Question 10

One inherited cause of recurrent angioedema?

• Inheritance?
• Genetic cause?

Answer 10

Hereditary Angioneurotic Edema (HAE)

Autosomal dominant

Question 11

Genetic cause of hereditary angioedema type I and type II?

Answer 11

SERPING1 gene mutation causes hereditary angioedema type I and type II

SERPING1 codes for C1 inhibitor that blocks pro-inflammatory proteins.
Type I = reduced C1 inhibitor
Type II = Produce abnormal C1 inhibitor

Question 12

Genetic cause of hereditary angioedema type III

Answer 12

Type III = F12 gene mutation coding for coagulation factor XII. High Factor XII = produce more bradykinin = more vascular permeability

Question 13

Clinical presentation of chronic granulomatous disease?

Answer 13

Recurrent bacterial and fungal infections

Pneumonia mostly, by S. aureus, Aspergillus or enteric bacteria

Cutaneous abscess

Lymphadenitis

Question 14

Clinical presentation of hereditary angioedema

Answer 14

Recurrent angioedema at lips, head and neck
Strong asso. abdominal pain
Triggered by stress
Intermittent urticaria

C1 inhibitors low or abnormal in blood

Question 15

Lymphocyte profile for chronic granulomatous disease?

Answer 15

High B-cells
Low CD8 T-killer cells

High CD4:CD8 ratio

Question 16

Special test for WBCs in chronic granulomatous disease?

Answer 16

Dihydrorhodamine reduction test

Shows impaired neutrophil respiratory burst activity

Question 17

Genetic cause of chronic granulomatous disease?

Answer 17

Mutation in NADPH oxidase&raquo_space; fail to make ROS in phagocytes&raquo_space;
Failure of phagocytes to kill pathogens

Mutation in any of the 5 subunits of NADPH oxidase
CYBB 
CYBA
NCF1
NCF2 
NCF4