Etiology and Pathophysiology
Epidemiology and etiology
- Genetic disorder with autosomal recessive inheritance
- Deficiency of 1 of the terminal complement proteins
- Most common deficiencies in the United States: C5, C6, or C8
Membrane attack complex (MAC) structure and function:
- Structure: ring-like structure formed by activated terminal complement proteins (C5b, C6, C7, C8, and C9)
- Attaches to the bacterial membrane to create pores
- Produces free diffusion between the intracellular and extracellular components, leading to microorganism lysis
- Decreased ability to create bacterial cell membrane pores leads to poor microorganism lysis.
- Increased susceptibility to encapsulated organisms
Most patients are asymptomatic.
Symptomatic patients present with:
- Recurrent encapsulated bacterial infections:
- Meningococcal infections
- Gonococcal infections
- Severe, disseminated neisserial infection:
- Sepsis and septic shock
Diagnosis and Management
Total complement activity (CH50) is used for screening. If CH50 is low/undetectable, measurement of the serum protein level for complement proteins should be ordered. Findings include:
- CH50: undetectable to low
- C3 level: normal
- C4 level: normal
- ≥ 1 of the late complement proteins is deficient.
- Treat infections aggressively with antibiotics.
- Vaccination against encapsulated bacteria:
- Haemophilus influenzae type b
- Bacterial sepsis/septic shock: a life-threatening syndrome that can be caused by bacterial infections. Sepsis is a generalized immune response that may result in organ dysfunction or failure. The best/fastest way to assess organ dysfunction in patients with a possible infection is the “quick Sequential Organ Failure Assessment (qSOFA).
- Hypogammaglobulinemia: refers to a laboratory finding (low IgG) that may be asymptomatic or that can be related to a number of clinical situations with different causes and manifestations if it’s more severe. Hypogammaglobulinemia can be caused by a primary immune deficiency or can be secondary to other diseases. The main feature of symptomatic hypogammaglobulinemia is repeated infections that normally are prevented by antibody responses.
- Meningococcemia: defined as dissemination of meningococci (Neisseria meningitidis) into the bloodstream. Patients with acute meningococcemia may present with meningitis, meningitis with meningococcemia, or meningococcemia without clinically apparent meningitis.
- Liszewski, M.K., et al. (2020). Inherited disorders of the complement system. In Schur, P.H., et al. (Ed.), UpToDate. Retrieved May 25, 2021, from https://www.uptodate.com/contents/inherited-disorders-of-the-complement-system
- Liszewski, M.K., et al. (2020). Overview and clinical assessment of the complement system. In Schur, P.H., et al. (Ed.), UpToDate. Retrieved May 25, 2021, from https://www.uptodate.com/contents/overview-and-clinical-assessment-of-the-complement-system
- Fischer, A. (2018). Primary immune deficiency diseases. Chapter 344 of Jameson JL, et al. (Ed.), Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.