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Journal of Clinical Immunology

, Volume 33, Issue 8, pp 1293–1301 | Cite as

Complete Factor I Deficiency Due to Dysfunctional Factor I with Recurrent Aseptic Meningo-Encephalitis

  • Filomeen Haerynck
  • Patrick Stordeur
  • Johan Vandewalle
  • Rudy Van Coster
  • Victoria Bordon
  • Frans De Baets
  • Petra Schelstraete
  • Cédric Javaux
  • Marie-Rose Bouvry
  • Véronique Fremeaux-Bacchi
  • Joke Dehoorne
Original Research

Abstract

Purpose

Complement regulators control the activated complement system. Defects in this homeostasis can result in tissue damage and autoimmune diseases with a heterogeneity in clinical presentation. Complement factor I (FI), a serine protease, is an important regulator of alternative pathway activation. We report a diagnostic work-up of a patient with relapsing inflammatory mediated meningo-encephalitis. Our work-up revealed a rare genetic factor I (FI) deficiency. So far, all cases of reported complete factor I deficiency have absent serum levels of FI. We present here a unique case of a complete factor I deficiency based on a functional FI defect.

Methods

Complement assays and measurement of FI activity were performed in the patient, her family, factor H-deficient patients, a patient with C3-nephritic factor and 11 healthy controls. Genetic sequencing of the FI coding regions in the patient and her parents was performed.

Results

The patient had absent alternative pathway activity with low levels of C3 and normal serum level of FI. The patient’s plasma FI did not degrade C3b, with normalisation of C3b degradation after adding purified FI. Mutation analysis of the complement factor I gene revealed two heterozygous mutations (I322T and D506V).

Conclusion

To our knowledge, this paper describes a complete FI deficiency caused by a defect of FI activity for the first time. Normal FI concentration does not exclude a complete FI defect, additional functional analysis of FI is required in any patient with a defect of complement activation. Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.

Keywords

Complete complement factor I deficiency Dysfunctional factor I Complement factor I gene mutation Aseptic meningo-encephalitis Alternative pathway regulators Immune-mediated vasculitis Complement 

Abbreviations

AP50

Alternative pathway activity

aHUS

Atypical haemolytic uremic syndrome

CSF

Cerebrospinal fluid

CH50

Classical pathway activity

C1

Complement factor 1

C3

Complement factor 3

C4BP

Complement factor 4 binding protein

CR1

Complement receptor 1

FB

Complement factor B

FBb

Complement factor Bb

FD

Complement factor D

FDG-PET scan

FluoroDeoxyGlucose-Position Emission Tomography

FI

Complement factor I

FIMAC

Factor I membrane attack complex

FH

Complement factor H

iC3b

Inactivated C3b

LDLr-1 and 2

Low-density lipoprotein receptor 1 and 2 domains

MAC

Membrane attack complex

MBL

Mannose binding lectin

MCP

Membrane cofactor protein

MRI

Magnetic Resonance Imaging

PCR

Polymerase chain reaction

PE

plasma exchange

SP

Serine protease domain

sSRBC

Sensitized sheep red blood cells

Notes

Acknowledgments

We thank Prof. Dr. Françoise Mascart (Immunobiology Laboratory, Erasme Hospital, Université Libre de Bruxelles, Belgium) for her support for the complement assays and Dr. Van den Kar and Dr. Van den Heuvel (Nijmegen, the Netherlands) for the MCP and FH gene sequencing. We also thank Ilse Coomans for the technical support.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Filomeen Haerynck
    • 1
  • Patrick Stordeur
    • 2
  • Johan Vandewalle
    • 3
  • Rudy Van Coster
    • 4
  • Victoria Bordon
    • 5
  • Frans De Baets
    • 1
  • Petra Schelstraete
    • 1
  • Cédric Javaux
    • 6
  • Marie-Rose Bouvry
    • 2
  • Véronique Fremeaux-Bacchi
    • 7
  • Joke Dehoorne
    • 3
  1. 1.Pediatric Pulmonology and ImmunologyGhent University HospitalGhentBelgium
  2. 2.Immunochemistry Laboratory, Immunobiology Clinics, Erasme HospitalUniversité Libre de BruxellesBrusselsBelgium
  3. 3.Pediatric Nephrology and RheumatologyGhent University HospitalGhentBelgium
  4. 4.Pediatric NeurologyGhent University HospitalGhentBelgium
  5. 5.Pediatric Hemato-oncology and ImmunologyGhent University HospitalGhentBelgium
  6. 6.Faculté de Médecine, Protein Chemistry UnitUniversité Libre de BruxellesBrusselsBelgium
  7. 7.Department of ImmunobiologyAssistance Publique-Hôpitaux de Paris, European Georges Pompidou HospitalParisFrance

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