Clinical Outcome and Underlying Genetic Cause of Functional Terminal Complement Pathway Deficiencies in a Multicenter...

Area of Science:

• Immunology
• Genetics

Background:

• Terminal complement pathway deficiencies are rare conditions associated with severe, recurrent infections.
• High-quality data on these deficiencies are limited.
• This study addresses the need for better understanding of clinical outcomes and genetic variations in a large UK cohort.

Purpose of the Study:

• To investigate the clinical outcomes and genetic variations in patients with primary and secondary terminal complement deficiencies.
• To analyze demographic, clinical, and laboratory data from a multi-center UK cohort.
• To identify patterns and risk factors associated with these deficiencies.

Main Methods:

• Data collection from seven UK centers on anonymized patient information.
• Collated and analyzed demographic, clinical, and laboratory data.
• Focused on patients with primary and secondary terminal complement deficiencies.

Main Results:

• Forty patients with terminal complement deficiencies were identified (median age 19 years).
• Low C5 concentrations were linked to CFH or CFI gene variants in 62% of patients.
• Infections primarily involved meningococcal serotypes B and Y; 22% required intensive care for meningococcal septicemia.
• 52% of patients were asymptomatic, diagnosed via family history.
• Most patients received meningococcal vaccines, and 70% were on prophylactic antibiotics.

Conclusions:

• The genetic etiology and clinical course of terminal complement deficiencies are highly variable.
• Low C5 levels necessitate genetic testing to rule out consumption due to regulatory defects.
• Screening of siblings is crucial for early diagnosis and management.
• Despite variable severity, a clear management plan is essential for all affected individuals.