Spectrum and Management of Complement Immunodeficiencies (Excluding Hereditary Angioedema) Across Europe
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Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management.
Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software.
Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects (p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects.
The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients.
KeywordsComplement immunodeficiency meningococcemia Streptococcus pneumoniae atypical hemolytic uremic syndrome glomerulopathy vaccination antibiotics
Atypical hemolytic uremic syndrome
European Society for Immunodeficiencies
Gain of function
Mannose binding lectin
Membrane cofactor protein
Paroxysmal noctural hemoglobinuria
Systemic lupus erythematosus
Declaration of interests
The authors declare no conflict of interests relevant to this study
PDA conceived of and led the study. AT collected and collated all the data. All authors contributed to collation and submission of their centre’s data and to the writing of the final version of the manuscript.
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