Allergy and immunology symposium Flashcards
What is C1 inhibitor deficiency also known as?
Hereditary angioedema
What is the characteristic feature of C1 inhibitor deficiency\?
Recurrent attacks of cutaneous and submucosal swelling
Also get abdominal attacks due to swelling in abdominal viscera
What is the prevalence of C1 inhibitor deficiency?
Between 1 in 25,000 to 1 in 100,00
What are some common causes of angioedema?
Spontaneous Autoimmune Drug-induced Physical Allergy
What other symptom is angioedema commonly associated with?
Urticaria
What is the genetic inheritance of C1 inhibitor deficiency?
Autosomal dominant
Describe the onset of C1 inhibitor deficiency
Infants and children are often asymptomatic or only mildly affected
Some people are symptomatic throughout their life
What can precipitate an attack?
Trauma (commonly dental or surgical)
Infection
Describe the role of C1 inhibitor protein
Binds to activated C1r and C1s which then dissociate from C1q
C1r and C1s are then free in solution and are no longer stable so they break down leading to inactivation
Only a strong stimulus that generates lots of C1s will lead to full activation
What happens in the absence of C1 inhibitor?
Excessive activation of classical complement pathway and low levels of C2 and C4
Describe type 1 HAE
Deletions / missense mutations in C1 inhibitor gene
Low C1 inhibitor protein levels
Describe type 2 HAE
Point mutations at active site
Normal / high levels of dysfunctional protein
How is HAE diagnosed?
Clinical history of attacks of swelling and/or abdominal pain without urticaria
Check serum C4 levels
- normal levels then HAE is excluded
- if low, proceed to test for C1 inhibitor protein levels and functional activity
What is acquired C1 inhibitor deficiency?
Very rare, non-genetic causes C1 inhibitor deficiency
Occurs in 2 settings: SLE, monoclonal B-cell disorders with paraproteins
How are acute attacks treated?
C1 inhibitor concentrate
