Antibody Deficiency Flashcards
Presentation:
What are common sites for infection?
What does recurrent infections cause long term?
Primary encapsulated bacteria such as Strep pneumonia, Haemophillus, Klebsiella.
They have a POLYSACCHARIDE CAPSULE.
Why is this important to know in antibody deficiency?
End organ damage - bronchiectasis
Chest
Sinuses (resp tract)
Ears and eyes
Phagocytes (macrophages and neutrophils) cannot phagocytose them due to the capsule.
Antibodies need to be used instead to cause ‘opsonisation’, which enhances phagocytosis
Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes. Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other.
If you are deficient, this process won’t happen increasing your risk of infection.
Presentation:
Why do viruses recur?
What disease occurs in childhood?
What antibody deficiency occurs at a range of ages?
Lack of protective immunity formed (recurrent shingles)
XLA - 3- 6 months after maternal IgG antibodies are lost
CVID
Non-infectious complications - read
Autoimmunity (e.g. autoimmune cytopenias / anaemia, endocrine, rheumatological e.g. SLE-like etc.)
Enteropathy (Coeliac-like condition not gluten sensitive, IBD)
Granulomatous inflammation
Sarcoid-like granulomatous lung disease (GLILD)
Lymphoproliferation, hepatosplenomegaly
Malignancy, particularly lymphoma
Secondary Antibody Deficiency - MORE COMMON
What drugs can cause this?
Malignancy? - 2
Loss - 2 reasons
Nutritional - 1
What infections can cause this?
Extremes of age as well
Cytotoxics
Anti-convulsatns
DMARDS
Rituximab
Malignancy (CLL, myeloma)
Gut - enteropathy
Kidney - nephrotic syndrome
B12
HIV
CMV
EBV
Secondary Antibody Deficiency - MORE COMMON
Why would you do FBC? - 5
Why would you do biochemistry?
FBC:
- Anaemia of chronic disease
- Evidence of bone marrow failure
- Thrombocytopenia
- WCC - neutropenia
- Blood film - abnormal cells, blasts - CLL
- Electrophoresis - myeloma
Biochemistry:
LFTs - albumin - renal or GI loss Thyroid function Creatinine and urea (renal disease) Blood glucose (DM) Urine dipstick - proteinuria
Immunoglobulins:
3 types?
IgG, IgA, IgM
Normal levels do not exclude significant immunodeficiency
Always have at least 2 separate measurements of serum immunoglobulins if low.
Low serum immunoglobulins do not automatically mean that immunoglobulin replacement therapy is required as can be well tolerated.
Investigations continued after looking for secondary causes:
Cytometry - Lymphocyte analysis
B cells are CD____ or CD____?
CD19/20
For CVID, consider markers to identify memory and class-switched memory B cells (low in more severe disease)
- CD27, CD19
- IgM, IgD
X-linked Agammaglobulinaemia:
Name of mutation?
What is defective?
How does it cause disease?
Sex more common in?
Typical presentation?
Type of pathogens causing disease? - 2
Treatment:
Lifelong Ig replacement:
- Route - 2
- What may be added?
- What are you trying to prevent?
- What may be added if needed?
What should be avoided?
Strep pneumonia, Haemophilus influenza
BTK mutation
BTK involved in signalling pre-BCR and BCR
Absence causes block in maturation
No mature B cells form
NO ANTIBODIES
MEN - X-LINKED
U/LRTI
SC or IV
End organ damage - bronchiectasis
Prophylactic ABs
NO live vaccines
Common Variable Immunodeficiency:
What Ig is low?
Can present in childhood until well into adulthood.
Diagnosis can be delayed!
Diagnostic Criteria:
- After what age is it diagnosed?
IgG mainly (and IgA)
After 4th yr of life
CVID manifestations - read!
Bacterial infections, as with XLA
Autoimmune disease
Enteropathy, Coeliac-like,
Malabsorption
Lymphoproliferation
Sarcoid-like granulomatous disease, can affect any organ
Granulomatous lymphocytic interstitial lung disease (GLILD)
Liver disease (nodular regenerative hyperplasia)
Malignancy, especially lymphoma (40 fold increased risk)
CVID:
Treatment:
Ig replacement + prophylactic ABs
What needs to be monitored for?
What can be tried as potentially curative treatment but is dangerous?
Need to look for malignancy - LYMPHOMA
Haematopoietic stem cell transplantation
Specific Antibody Deficiency (SpAD):
How is this different from CVID and XLA?
By definition IgG, IgA and IgM levels are NORMAL!
What 2 tests are done for this?
What needs to be ruled out to rule out combined immunodeficiency?
Treatment - ABs + Ig if needed
Normal total antibody levels, but fail to produce antibodies to CERTAIN TYPES of antigens (particularly polysaccharide)
Look for specific bacterial antibodies - Pneumococcus and Tetanus
If LOW, test vaccine can be given and it is measured weeks later.
Failure to respond suggest SpAD
T cell defect
Selective IgA Deficiency:
Usually found incidentally on Coeliac screening
In absence of recurrent infection no further investigation needed
Not huge - IgM compensates for IgA
Selective IgA Deficiency:
Usually found incidentally on Coeliac screening
In absence of recurrent infection no further investigation needed
Not huge - IgM compensates for IgA
