Format

Send to

Choose Destination
J Clin Immunol. 2017 Nov;37(8):781-789. doi: 10.1007/s10875-017-0447-x. Epub 2017 Sep 23.

Early Versus Late Diagnosis of Complement Factor I Deficiency: Clinical Consequences Illustrated in Two Families with Novel Homozygous CFI Mutations.

Author information

1
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain.
2
Jeffrey Model Foundation Excellence Center, Barcelona, Catalonia, Spain.
3
Research Unit in Translational Bioinformatics, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.
4
Adult Immunodeficiencies Unit (UFIPA), Internal Medicine Department, Hospital Universitari de Bellvitge (HUB), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Catalonia, Spain.
5
Immunology Laboratory, Hospital de Bellvitge, Barcelona, Catalonia, Spain.
6
Pediatric Infectious Diseases and Immunodeficiencies Unit (UPIIP), Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.
7
ICREA, Barcelona, Catalonia, Spain.
8
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain. rcolobran@vhebron.net.
9
Jeffrey Model Foundation Excellence Center, Barcelona, Catalonia, Spain. rcolobran@vhebron.net.
10
Servei d'Immunologia. Edifici Laboratoris, Planta Baixa, Hospital Universitari Vall d'Hebron (HUVH), Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. rcolobran@vhebron.net.

Abstract

The complement system is an important effector arm of innate immunity and plays a crucial role in the defense against common pathogens. But effective defense and maintenance of homeostasis requires a careful balance between complement activation and regulation. Factor I (FI) is one of the most important regulators of the complement system. Complete FI deficiency is a rare autosomal recessive disorder typically resulting in severe, recurrent infection by encapsulated bacteria. In the present study, we describe two patients from unrelated families with complete FI deficiency diagnosed at very different ages: Patient 1 is a 60-year-old man who had experienced several severe infections (pneumonia, meningitis, sepsis) since childhood, one of which caused significant and permanent neurologic sequelae. In contrast, patient 2 was diagnosed at the age of 4 years after a single infectious episode (otitis media) and through detection of a flat beta2 peak on serum protein electrophoresis. This early diagnosis of FI deficiency enabled prompt implementation of a therapeutic intervention consisting of vaccination with encapsulated bacteria and prophylactic antibiotics. The two patients had novel homozygous mutations in the CFI gene (p.Gly162Asp and p.His380Arg) that disrupted protein function. Interestingly, p.His380Arg is the first mutation described affecting a residue of the highly conserved FI catalytic triad (His380, Asp429, and Ser525). This study illustrates the importance of early versus late diagnosis of FI deficiency and, in general, highlights the clinical relevance of prompt detection of complement system deficiencies.

KEYWORDS:

Complement system; Early diagnosis; Factor I deficiency; Late diagnosis; Meningitis; Mutations; Pneumonia; Primary immunodeficiencies; Sepsis

PMID:
28942469
DOI:
10.1007/s10875-017-0447-x
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center