Immunology - Complement Disorders

Question 1

What are complement disorders?

Answer 1

Disorders affecting complement proteins that make up the complement system which help destroy pathogenic cells

Question 2

What are the main functions of the complement system?

Answer 2

Opsonisation of pathogens
Recruitment of inflammatory cells
Direct killing via membrane attack complex (MAC)
Clearance of immune complexes

Question 3

What type of organisms are complement proteins crucial for dealing with?

Answer 3

Encapsulated bacteria and Neisseria species

Complement is important for:
Opsonisation of encapsulated organisms
Membrane attack complex killing of Neisseria

Question 4

Which complement deficiencies are associated with recurrent Neisseria infections?

Answer 4

Terminal complement deficiencies:
C5
C6
C7
C8
C9

Impaired membrane attack complex formation

Question 5

What are some examples of encapsulated organisms?

Answer 5

Haemophilus influenza B
Streptococcus pneumonia
Neisseria meningitidis

Question 6

What do complement deficiencies cause in children?

Answer 6

Increased susceptibility to recurrent bacterial infections

Particularly:
Respiratory tract infections
Otitis media
Sinusitis

Terminal complement deficiencies predispose to recurrent Neisseria infections

Question 7

What are complement deficiencies also associated with?

Answer 7

Immune complex disorders e.g. SLE

Question 8

Which complement deficiencies are associated with autoimmune disease?

Answer 8

Early classical pathway deficiencies:
C1
C2
C4

Associated with immune complex diseases such as SLE

Question 9

Why are complement deficiencies associated with immune complex disorders?

Answer 9

Immune complexes build up and are deposited in tissues

This causes chronic inflammation

C2 deficiency is the most common

Question 10

What is extremely important for all children with complement disorders?

Answer 10

Vaccination against encapsulated organisms

Question 11

What is C1 Esterase Inhibitor Deficiency?

Answer 11

AKA Hereditary Angioedema

Deficiency or dysfunction of C1 esterase inhibitor

Leads to excessive bradykinin production causing:
Increased vascular permeability
Recurrent non-urticarial angioedema

Question 12

What can trigger intermittent angioedema?

Answer 12

Minor triggers e.g. viral infections, stress or no clear reason

Question 13

Where does angioedema affect?

Answer 13

Lips or face

Can occur anywhere on the body including respiratory and GI tract

Can also occur in larynx and compromise the airway

Question 14

How does hereditary angioedema differ from allergic angioedema?

Answer 14

• No urticaria or itching
• Bradykinin-mediated not histamine-mediated
• Does not respond to antihistamines or adrenaline
• Often triggered by stress or trauma

Question 15

How can patients with hereditary angioedema be treated?

Answer 15

C1 esterase inhibitor concentrate

Bradykinin pathway treatments e.g. icatibant

Short-term prophylaxis before procedures

Adrenaline, antihistamines and steroids are usually ineffective

Question 16

What is the key test for diagnosing hereditary angioedema?

Answer 16

Check C4 levels

C4 levels are low in C1 esterase inhibitor deficiency

Question 17

What is mannose-binding lectin deficiency?

Answer 17

Relatively common complement deficiency affecting the lectin pathway

Often asymptomatic

May predispose to recurrent infections in infancy or in patients with other conditions