Primary Immune Deficiencies 2

Question 1

What is the aetiology ofd reticular dysgenesis?

Answer 1

Most severe form of SCID

Mutation in AK2 (mitochondrial energy enzyme ADENYLATE KINASE 2)

Question 2

What does reticular dysgenesis result in?

Answer 2

failure in production of ALL cells

lymphocytes, neutrophils, monocytes/macrophages, platelets

Question 3

What does X linked SCID present as?

Answer 3

No T cells
Normal/increased B cells (but low Ig)
No NK cells

Question 4

What is the mutation in X linked SCID?

Answer 4

mutation of the gamma common chain on chromosome Xq13.1

Leads to early arrest of T cell and NK cell development, and production of immature B cells

Question 5

What is ADA deficiency

Answer 5

Adenosine deaminase deficiency (required for cell metabolism)

Question 6

What does ADA deficiency present as?

Answer 6

No T cells
No B cells
No NK cells

Question 7

What deletion causes Di George Syndrome?

Answer 7

22q11.2

Question 8

Explain the aetiology for Di George Syndrome

Answer 8

The thymus does not fully develop
Due to developmental defect of the pharyngeal pouch
(also the parathyroid gland does not develop > low PTH > low Ca)

Question 9

What do children with Di George Look like?

Answer 9

High forehead
Low set, abnormally folded ears
Cleft palate
Small mouth and jaw

Question 10

What are the consequences of an underdeveloped thymus in Di George?

Answer 10

Low T cell
Normal B cells
Homeostatic proliferation with age (as T cells are in an empty compartment, they will keep proliferating so in the end T cell numbers will keep increasing with age)

Question 11

How does immune function change with age in Di George ?

Answer 11

Improves with age

Question 12

What gene is mutated in di George?

Answer 12

TBX1

Question 13

What is Bare Lymphocyte Syndrome caused by?

Answer 13

FAILURE OF EXPRESSION OF HLA/MHC molecules

defect in one of the regulatory proteins involved in expression of Class I/II MHC

This leads to inability to select CD4 T cells > T cell deficiency

Question 14

What is the immunology phenotype of BLS?

Answer 14

Normal CD8
Normal B cell
LOW IgG/IgA antibodies due to lack of CD4+ T cell help

Question 15

What its the clinical phenotype of BLS?

Answer 15

Unwell by 3 months
Infections of al type
Failure to thrive
Family history of early infant death

Question 16

what are the two types of BLS?

Answer 16

Type I: deficiency in MHC class 1
Type II: deficiency in MHC class 2

Question 17

What are investigations for T cell deficiencies?

Answer 17

Total WCC 
Lymphocyte subset (quantify CD4,CD8,B cell, NK cell)
Immunoglobulins (if CD4 def, they will have IgM but not IgG, IgA)

Question 18

What is management of immunodeficiency involving T cells?

Answer 18

Aggressive prophylaxis/tx of infection 
Hfaematopoeic SC transplant 
Enzyme replacement therapy 
Gene therapy 
Thymic transplantation

Question 19

What disease in thymic transplantation used for?

Answer 19

Di George

Question 20

What disease is enzyme replacement therapy used for?

Answer 20

ADA SCID

Give PEG-ADA

Question 21

What gene is Bruton’s X linked Hypogammaglobulinaemia caused by?

Answer 21

BTK gene (abnormal B tyrosine kinase gene)

Question 22

Explain the aetiology behind Bruton’s

Answer 22

There is an absence of mature B cells
Because Pre-B cells cannot mature into mature B cells
The issue is at the point at which B cells emerge from the bone marrow

Question 23

When does Bruton’s start causing symptoms ?

Answer 23

After 3 months, when maternal IgG leave the system

Question 24

What is the clinical phenotype of Bruton’s?

Answer 24

Recurrent bacterioal infections e.g. otitis media, sinusitis, pneumonia, osteomyelitis, gastroenteritis
Viral, fungal, parasitic infection
Failure to thrive

Question 25

What is the aetiology of Hyper IgM syndrome?

Answer 25

Blocked maturation of IgM B cells
The IgM B cells are unable to enter the germinal centre reaction due to mutation in CD40 ligand gene (technically a T cell problem)

Question 26

What is the immunological phenotype of Hyper IgM?

Answer 26

Normal circulating B cells
Normal T cells (but do NOT express CD40)
NO germinal cell development within lymph nodes and spleen
Failure of isotope switching
Elevated serum IgM, undetectable IgG, IgA, IgE

Question 27

What is the clinical phenotype of Hyper IgM?

Answer 27

Boys present within first few years
Recurrent bacterial infections
Predisposed to Pneumocisti Jirovecii, AI disease, malignancy
Failure to thrive

Question 28

What is common variable immunodeficiency?

Answer 28

LOW IgG, IgA, IgE
Recurrent bacterial infections
Cause is unknown

Question 29

What phenotypes does CVI present as?

Answer 29

Recurrent bacterial infections (often with severe end organ damage)
Pulmonary disease
GI disease (IBD-like, bacterial overgrowth)
AI disease (AIHA, thrombocytopenia, RA, Thyroiditis)
Malignancy (Non Hodgkins)

Question 30

What is the prevalence of IgA deficiency?

Answer 30

1 In 600

Question 31

What portion of people with IgA deficiency know they have it?

Answer 31

only 1/3rd

2/3 are asymptomatic

Question 32

What is management of immunodeficiency involving B cells?

Answer 32

Aggressive prophylaxis/tx of infection

Ig replacement if required (from donor plasma, tx is lifelong)

Question 33

Would you immunise someone with B cell immunodeficiency?

Answer 33

NO

because they will NOT be able to produce any antibodies (unless selective IgA deficiency)