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 #C5C9Deficiency #Complement #pathophysiology #immunology
