C5-C9 Deficiency - Pathogenesis and Clinical Findings

Note:

 • Risk of invasive meningococcal disease is 1000-10000x higher in C5-C9 deficiency than in the general population

 • C5-C9 deficient patients are not at greater risk for contracting other gram (-) infections

 • Clinical meningitis in C5-C9 deficiency is less severe and fatality is rare

Normal complement response:

The complement pathway is a non-specific response to bacterial pathogens

Bacterial infection -> Classical, alternative, or lectin pathway activation -> Complement cascade -> MAC formation on bacterial surface C5b, C6, C7, C8, C9 -> Complement proteins create transmembrane channels within bacterial cell walls/cell membranes -> Critical bacterial proteins leak out of the cell, breakdown of entire cell



C5-C9 deficiency

Inability to form MAC -> susceptibility to systemic Neisseria infection, Commonly N. meningitidis, Rarely N. monorrhoeae -> Nasopharyngeal colonization of N. meningitidis, Incr susceptibility to bacteremia

=> 

 • Bacteria cross the blood-brain barrier, causing swelling and damaging brain tissue -> Fatigue, fever, headache, altered mental status, etc.

 • Inflammation of CSF and meninges -> Activation of dura and pia mater fibres  -> Headache, neck stiffness

 • Bacteria release toxins -> Damage to surface blood vessels -> Maculopapular rash



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