Primary Immune Deficiencies 2 Flashcards
What is the aetiology ofd reticular dysgenesis?
Most severe form of SCID
Mutation in AK2 (mitochondrial energy enzyme ADENYLATE KINASE 2)
What does reticular dysgenesis result in?
failure in production of ALL cells
lymphocytes, neutrophils, monocytes/macrophages, platelets
What does X linked SCID present as?
No T cells
Normal/increased B cells (but low Ig)
No NK cells
What is the mutation in X linked SCID?
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
What is ADA deficiency
Adenosine deaminase deficiency (required for cell metabolism)
What does ADA deficiency present as?
No T cells
No B cells
No NK cells
What deletion causes Di George Syndrome?
22q11.2
Explain the aetiology for Di George Syndrome
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)
What do children with Di George Look like?
High forehead
Low set, abnormally folded ears
Cleft palate
Small mouth and jaw
What are the consequences of an underdeveloped thymus in Di George?
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)
How does immune function change with age in Di George ?
Improves with age
What gene is mutated in di George?
TBX1
What is Bare Lymphocyte Syndrome caused by?
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
What is the immunology phenotype of BLS?
Normal CD8
Normal B cell
LOW IgG/IgA antibodies due to lack of CD4+ T cell help
What its the clinical phenotype of BLS?
Unwell by 3 months
Infections of al type
Failure to thrive
Family history of early infant death
what are the two types of BLS?
Type I: deficiency in MHC class 1 Type II: deficiency in MHC class 2
What are investigations for T cell deficiencies?
Total WCC Lymphocyte subset (quantify CD4,CD8,B cell, NK cell) Immunoglobulins (if CD4 def, they will have IgM but not IgG, IgA)
What is management of immunodeficiency involving T cells?
Aggressive prophylaxis/tx of infection Hfaematopoeic SC transplant Enzyme replacement therapy Gene therapy Thymic transplantation
What disease in thymic transplantation used for?
Di George
What disease is enzyme replacement therapy used for?
ADA SCID
Give PEG-ADA
What gene is Bruton’s X linked Hypogammaglobulinaemia caused by?
BTK gene (abnormal B tyrosine kinase gene)
Explain the aetiology behind Bruton’s
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
When does Bruton’s start causing symptoms ?
After 3 months, when maternal IgG leave the system
What is the clinical phenotype of Bruton’s?
Recurrent bacterioal infections e.g. otitis media, sinusitis, pneumonia, osteomyelitis, gastroenteritis
Viral, fungal, parasitic infection
Failure to thrive
What is the aetiology of Hyper IgM syndrome?
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)
What is the immunological phenotype of Hyper IgM?
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
What is the clinical phenotype of Hyper IgM?
Boys present within first few years
Recurrent bacterial infections
Predisposed to Pneumocisti Jirovecii, AI disease, malignancy
Failure to thrive
What is common variable immunodeficiency?
LOW IgG, IgA, IgE
Recurrent bacterial infections
Cause is unknown
What phenotypes does CVI present as?
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)
What is the prevalence of IgA deficiency?
1 In 600
What portion of people with IgA deficiency know they have it?
only 1/3rd
2/3 are asymptomatic
What is management of immunodeficiency involving B cells?
Aggressive prophylaxis/tx of infection
Ig replacement if required (from donor plasma, tx is lifelong)
Would you immunise someone with B cell immunodeficiency?
NO
because they will NOT be able to produce any antibodies (unless selective IgA deficiency)
