C5-C9 deficiency: pathophysiology and clinical findings
Authors: Heather Yong Reviewers: Jessica Tjong, Crystal Liu, Yan Yu*, Nicola Wright* * MD at time of publication
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 trans-
membrane channels within bacterial cell walls/cell membranes
Critical bacterial proteins leak out of the cell, breakdown of entire cell
Primary (hereditary) causes Secondary (acquired) causes
All are autosomal recessive Biologic therapy ex. eculizumab Absence or suboptimal functioning of
Abbreviations:
• MAC: Membrane Attack
Complex
• CH50: Classic Hemolytic
Complement Test
• AH50: Alternative Hemolytic
Complement Test
• CNS: Central Nervous System • CSF: Cerebrospinal Fluid
≥1 terminal complement proteins
C5-C9 deficiency
Inability to form MAC
↑ susceptibility to systemic Neisseria infection
Commonly N. meningitidis Rarely N. monorrhoeae
Nasopharyngeal colonization of N. meningitidis, ↑ susceptibility to bacteremia
CH50 ± AH50 assay No lysis
Note:
Total complement activity assay <10% activity C5, C6, C7, C9 <50% activity C8 Varied bactericidal action via other complement proteins • Risk of invasive meningococcal disease is 1000-10000X higher in C5-C9 deficiency than in the general population • Reason is unknown • 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 Bacterial lysis Especially gram (-)ve bacteria like Neisseria 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 Exact mechanism unknown Recurrent meningitis CNS damage due Sepsis to recurrent meningitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2019 on www.thecalgaryguide.com