Clinical Outcome and Underlying Genetic Cause of Functional Terminal Complement Pathway Deficiencies in a Multicenter UK Cohort.
J Clin Immunol
; 42(3): 665-671, 2022 04.
Article
in English
| MEDLINE | ID: covidwho-1653614
ABSTRACT
BACKGROUND:
Terminal complement pathway deficiencies often present with severe and recurrent infections. There is a lack of good-quality data on these rare conditions. This study investigated the clinical outcome and genetic variation in a large UK multi-center cohort with primary and secondary terminal complement deficiencies.METHODS:
Clinicians from seven UK centers provided anonymised demographic, clinical, and laboratory data on patients with terminal complement deficiencies, which were collated and analysed.RESULTS:
Forty patients, median age 19 (range 3-62) years, were identified with terminal complement deficiencies. Ten (62%) of 16 patients with low serum C5 concentrations had underlying pathogenic CFH or CFI gene variants. Two-thirds were from consanguineous Asian families, and 80% had an affected family member. The median age of the first infection was 9 years. Forty-three percent suffered meningococcal serotype B and 43% serotype Y infections. Nine (22%) were treated in intensive care for meningococcal septicaemia. Two patients had died, one from intercurrent COVID-19. Twenty-one (52%) were asymptomatic and diagnosed based on family history. All but one patient had received booster meningococcal vaccines and 70% were taking prophylactic antibiotics.DISCUSSION:
The genetic etiology and clinical course of patients with primary and secondary terminal complement deficiency are variable. Patients with low antigenic C5 concentrations require genetic testing, as the low level may reflect consumption secondary to regulatory defects in the pathway. Screening of siblings is important. Only half of the patients develop septicaemia, but all should have a clear management plan.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sepsis
/
COVID-19
/
Meningococcal Infections
Type of study:
Cohort study
/
Diagnostic study
/
Etiology study
/
Observational study
/
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Middle aged
/
Young adult
Country/Region as subject:
Europa
Language:
English
Journal:
J Clin Immunol
Year:
2022
Document Type:
Article
Affiliation country:
S10875-022-01213-9
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