What is consistent with a person presenting with a genetic deficiency of the terminal complement cascade (C5-9), specifically affecting the membrane attack complex (MAC) formation?

From the Guidelines

Consistent Presentation

A person presenting with a genetic deficiency of the terminal complement cascade (C5-9), specifically affecting the membrane attack complex (MAC) formation, is consistently at increased risk for recurrent neisserial meningitis.

Key Points

• The terminal complement pathway, particularly components C5-9, plays a crucial role in forming the membrane attack complex (MAC) that helps to lyse pathogens, including Neisseria meningitidis 1.
• Deficiencies in the terminal complement components (C5-9) are associated with an increased risk of meningococcal disease, as the MAC is essential for the direct killing of Neisseria meningitidis 1.
• Antibiotic prophylaxis and immunization can be applied to manage and prevent recurrent infections in individuals with complement deficiencies, including those affecting the terminal complement cascade 1.
• The pattern of infections and the response to treatment are critical in evaluating immunodeficiency and distinguishing it from other conditions 1.

Management Considerations

• Routine vaccination with the quadrivalent vaccine is recommended for individuals with terminal complement component deficiencies to prevent meningococcal disease 1.
• Antibiotic prophylaxis regimens, such as those outlined in Table VII of the practice parameter for the diagnosis and management of primary immunodeficiency, may be considered for individuals with recurrent infections 1.

From the Research

Clinical Presentation

• A person presenting with a genetic deficiency of the terminal complement cascade (C5-9) is consistent with an increased susceptibility to infections, particularly those caused by Neisseria species, such as Neisseria gonorrhoeae and Neisseria meningitidis 2, 3, 4, 5, 6.
• The membrane attack complex (MAC) formation is essential for the lysis of Gram-negative bacteria, and deficiencies in terminal complement components can lead to impaired MAC formation and increased risk of infections 2, 3, 4.

Genetic Deficiencies

• Genetic deficiencies in C5, such as those caused by novel mutations, can lead to C5 deficiency and increased susceptibility to Neisseria infections 3.
• C9 deficiency can also lead to impaired MAC formation and increased risk of Neisseria infections 4.
• Other genetic deficiencies, such as those affecting the C6, C7, and C8 components, can also lead to terminal complement pathway deficiencies and increased risk of infections 5.

Clinical Outcomes

• Patients with terminal complement pathway deficiencies often present with severe and recurrent infections, including meningococcal septicemia 5.
• The clinical outcome and genetic variation in patients with terminal complement deficiencies can be variable, and patients may require genetic testing and screening of siblings 5.
• Prophylactic antibiotics and booster meningococcal vaccines may be necessary to prevent infections in patients with terminal complement pathway deficiencies 5.