Immuno: Primary Immune Deficiencies Pt.2 Flashcards
For each of the following conditions, state the stereotypical presentation:
- Kostmann syndrome
- Leucocyte adhesion deficiency
- Chronic granulomatous disease
- IFN-gamma receptor deficiency
- Classical NK cell deficiency
- Kostmann syndrome
- Recurrent infections with NO neutrophils on FBC
- Leucocyte adhesion deficiency
- Recurrent infections with HIGH neutrophils on FBC and no pus formation
- Chronic granulomatous disease
- Recurrent infections with hepatosplenomegaly and abnormal DHR
- IFN-gamma receptor deficiency
- Infection with atypical mycobacteria
- Normal FBC
- Classical NK cell deficiency
- Severe viral infections (e.g. chickenpox, disseminated CMV)
What is factor H?
A regulatory protein in the alternative complment pathway
What is the main clinical consequence of complement deficiency?
Increased susceptibility to infection by encapsulated bacteria
(Alternative pathway)
Which encapsulated bacteria are particularly problematic in patients with complement deficiency?
- Neisseria meningitidis
- Haemophilius influenzae
- Streptococcus pneumoniae
NOTE: susceptibility to N. meningitidis is particularly common in properidin and C5-9 deficiency
What are the consequences of MBL deficiency?
Common but NOT associated with immunodeficiency
Why are deficiencies in early classical complement pathway components associated with SLE?
- The classical complement pathway promotes phagocyte-mediated clearance of apoptotic/necrotic cells
- Deficiencies in this pathway lead to ineffective clearance of apoptotic/necrotic cells leading to an increase in self-antigens and, hence, autoantibodies
- The classical complement pathway also promotes clearance of immune complexes
- So, complement deficiency can lead to deposition of immune complexes which stimulate local inflammation in the skin, joints and kidneys
List some different complement deficiencies and state which is most common.
- C1q
- C1r
- C1s
- C2 - MOST COMMON
- C4
Outline the clinical phenotype of complement deficiency.
- Almost all patients with C2 deficiency have SLE
- Usually have severe skin disease
- Increased risk of infection
How does SLE lead to a functional complement deficiency?
- Active lupus causes persistent production of immune complexes
- This leads to consumption of complement components leading to a functional complement deficiency
- C3 and C4 will be low
What are nephritic factors?
Autoantibodies that are directed against components of the complement pathway
- They stabilise C3 convertases resulting in C3 activation and consumption
What disease is associated with the presence of nephritic factors?
- Glomerulonephritis (usually membranoproliferative)
- It may also be associated with partial lipodystrophy
Which complement components may be measured in assays and why?
- C3 and C4 are measured routinely to monitor SLE (low in active lupus)
- C1 esterase inhibitor - decreased in hereditary angio-oedema
Name two functional complement assays and describe what they are testing.
- CH50 - test of classical pathway (C1, 2, 4, 3, 5-9)
- AP50 - test of the alternative pathway (B, D, Properidin, C3, C5-9)
Outline the management of complement deficiencies.
- Vaccination (especially against encapsulated organisms)
- Prophylactic antibiotics
- Treat infection aggressively
- Screen family members
Describe the stereotypical presentation of the following diseases:
- C1q deficiency
- C3 deficiency with nephritic factor
- C7 deficiency
- MBL deficiency
- C1q deficiency
- Severe childhood-onset SLE with normal levels of C3 and C4
- C3 deficiency with nephritic factor
- Membranoproliferative nephritis with abnormal fat distribution (partial lipodystrophy)
- C7 deficiency
- Meningococcus meningitis with a family history of a sibling dying aged 6
- MBL deficiency
- Recurrent infections when neutropaenic following chemotherapy, but previously well
