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Journal of Clinical Immunology

, Volume 35, Issue 2, pp 199–205 | Cite as

Spectrum and Management of Complement Immunodeficiencies (Excluding Hereditary Angioedema) Across Europe

  • A. J. Turley
  • B. Gathmann
  • C. Bangs
  • M. Bradbury
  • S. Seneviratne
  • L. I. Gonzalez-Granado
  • S. Hackett
  • N. Kutukculer
  • H. Alachkar
  • S. Hambleton
  • H. Ritterbusch
  • P. Kralickova
  • L. Marodi
  • M. G. Seidel
  • G. Dueckers
  • J. Roesler
  • A. Huissoon
  • H. Baxendale
  • J. Litzman
  • P. D. ArkwrightEmail author
Original Research

Abstract

Introduction

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.

Methods

Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software.

Results

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.

Conclusion

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.

Keywords

Complement immunodeficiency meningococcemia Streptococcus pneumoniae atypical hemolytic uremic syndrome glomerulopathy vaccination antibiotics 

Abbreviations

aHUS

Atypical hemolytic uremic syndrome

ESID

European Society for Immunodeficiencies

GOF

Gain of function

HAE

Hereditary angioedema

MBL

Mannose binding lectin

MCP

Membrane cofactor protein

PNH

Paroxysmal noctural hemoglobinuria

SLE

Systemic lupus erythematosus

Notes

Declaration of interests

The authors declare no conflict of interests relevant to this study

Author contribution

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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • A. J. Turley
    • 1
  • B. Gathmann
    • 2
  • C. Bangs
    • 3
  • M. Bradbury
    • 4
  • S. Seneviratne
    • 5
  • L. I. Gonzalez-Granado
    • 6
  • S. Hackett
    • 7
  • N. Kutukculer
    • 8
  • H. Alachkar
    • 9
  • S. Hambleton
    • 10
  • H. Ritterbusch
    • 2
  • P. Kralickova
    • 11
  • L. Marodi
    • 12
  • M. G. Seidel
    • 13
  • G. Dueckers
    • 14
  • J. Roesler
    • 15
  • A. Huissoon
    • 16
  • H. Baxendale
    • 17
  • J. Litzman
    • 18
  • P. D. Arkwright
    • 19
    • 20
    Email author
  1. 1.Paediatric ImmunologyUniversity of ManchesterManchesterUK
  2. 2.For the ESID Registry working party, Center for Chronic Immunodeficiency (CCI)University Medical Centre Freiburg and University of FreiburgFreiburgGermany
  3. 3.Immunology, Royal Manchester InfirmaryManchesterUK
  4. 4.Paediatric NephrologyRoyal Manchester Children’s HospitalManchesterUK
  5. 5.Immunology, Royal Free HospitalLondonUK
  6. 6.Pediatric Immunodeficiencies UnitHospital Universitario 12 OctubreMadridSpain
  7. 7.Paediatric ImmunologyBirmingham HeartlandsBirminghamUK
  8. 8.Paediatric ImmunologyEge UniversityIzmirTurkey
  9. 9.Immunology, Salford Royal Foundation TrustManchesterUK
  10. 10.Paediatric ImmunologyUniversity of NewcastleNewcastleUK
  11. 11.Allergology & Clinical ImmunologyFaculty Hospital Hradec KraloveHradec KraloveCzech Republic
  12. 12.Medical & Health Science CenterUniversity of DebrecenDebrecenHungary
  13. 13.Pediatric Hematology-OncologyMedical University-GrazGrazAustria
  14. 14.HELIOS ClinicChildrens Hospital KrefeldKrefeldGermany
  15. 15.Kinder und JugendmedizinUniversitatsklinkkum Carl Gustav CarusDresdenGermany
  16. 16.Immunology, Birmingham Heartlands HospitalBirminghamUK
  17. 17.Immunology, Addenbrookes HospitalCambridgeUK
  18. 18.Clinical Immunology & Allergology, St. Anne’s University Hospital and Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  19. 19.Paediatric ImmunologyRoyal Manchester Children’s HospitalManchesterUK
  20. 20.Department of Paediatric Allergy and ImmunologyRoyal Manchester Children’s HospitalManchesterUK

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