Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report

Affiliations

¹ From the Weill Institute for Neurosciences (M.R., M.R.W.), Department of Neurology, University of California, San Francisco; Montreal Neurological Institute and Hospital (A.H.), Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada; Department of Biochemistry and Biophysics (K.C.Z., A.T.); Department of Laboratory Medicine (C.O., C.Y.C.); Kaiser Permanente Santa Rosa Medical Center (K.K.)Department of Medicine (M.M.), Division of Rheumatology; Department of Medicine (A.B.), Molecular Medicine Consult Service; Department of Medicine (C.Y.C.), Division of Infectious Diseases, University of California, San Francisco; The Peter Doherty Institute for Infection and Immunity (P.S.R.); Department of Neurology (P.S.R.), Royal Melbourne Hospital; and Department of Neurology (P.S.R.), St.Vincent's Hospital, University of Melbourne, Australia.
² From the Weill Institute for Neurosciences (M.R., M.R.W.), Department of Neurology, University of California, San Francisco; Montreal Neurological Institute and Hospital (A.H.), Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada; Department of Biochemistry and Biophysics (K.C.Z., A.T.); Department of Laboratory Medicine (C.O., C.Y.C.); Kaiser Permanente Santa Rosa Medical Center (K.K.)Department of Medicine (M.M.), Division of Rheumatology; Department of Medicine (A.B.), Molecular Medicine Consult Service; Department of Medicine (C.Y.C.), Division of Infectious Diseases, University of California, San Francisco; The Peter Doherty Institute for Infection and Immunity (P.S.R.); Department of Neurology (P.S.R.), Royal Melbourne Hospital; and Department of Neurology (P.S.R.), St.Vincent's Hospital, University of Melbourne, Australia. pramachandra@unimelb.edu.au.

PMID: 37339889
PMCID: PMC10282980
DOI: 10.1212/NXI.0000000000200121

Case Reports

Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report

Mary Rolfes et al. Neurol Neuroimmunol Neuroinflamm. 2023.

. 2023 Jun 20;10(5):e200121.

doi: 10.1212/NXI.0000000000200121. Print 2023 Sep.

Affiliations

¹ From the Weill Institute for Neurosciences (M.R., M.R.W.), Department of Neurology, University of California, San Francisco; Montreal Neurological Institute and Hospital (A.H.), Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada; Department of Biochemistry and Biophysics (K.C.Z., A.T.); Department of Laboratory Medicine (C.O., C.Y.C.); Kaiser Permanente Santa Rosa Medical Center (K.K.)Department of Medicine (M.M.), Division of Rheumatology; Department of Medicine (A.B.), Molecular Medicine Consult Service; Department of Medicine (C.Y.C.), Division of Infectious Diseases, University of California, San Francisco; The Peter Doherty Institute for Infection and Immunity (P.S.R.); Department of Neurology (P.S.R.), Royal Melbourne Hospital; and Department of Neurology (P.S.R.), St.Vincent's Hospital, University of Melbourne, Australia.
² From the Weill Institute for Neurosciences (M.R., M.R.W.), Department of Neurology, University of California, San Francisco; Montreal Neurological Institute and Hospital (A.H.), Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada; Department of Biochemistry and Biophysics (K.C.Z., A.T.); Department of Laboratory Medicine (C.O., C.Y.C.); Kaiser Permanente Santa Rosa Medical Center (K.K.)Department of Medicine (M.M.), Division of Rheumatology; Department of Medicine (A.B.), Molecular Medicine Consult Service; Department of Medicine (C.Y.C.), Division of Infectious Diseases, University of California, San Francisco; The Peter Doherty Institute for Infection and Immunity (P.S.R.); Department of Neurology (P.S.R.), Royal Melbourne Hospital; and Department of Neurology (P.S.R.), St.Vincent's Hospital, University of Melbourne, Australia. pramachandra@unimelb.edu.au.

PMID: 37339889
PMCID: PMC10282980
DOI: 10.1212/NXI.0000000000200121

Abstract

Mutations in the complement factor I (CFI) gene have previously been identified as causes of recurrent CNS inflammation. We present a case of a 26-year-old man with 18 episodes of recurrent meningitis, who had a variant in CFI(c.859G>A,p.Gly287Arg) not previously associated with neurologic manifestations. He achieved remission with canakinumab, a human monoclonal antibody targeted at interleukin-1 beta.

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Conflict of interest statement

The authors report no relevant disclosures. Go to Neurology.org/NN for full disclosures.

Figures

**Figure 1. Brain MRI and Timeline of Meningitis Attacks and Treatment**
Coronal T2-weighted (A) and axial T2-weighted (B) images demonstrating symmetric T2 signal hyperintensities in the hippocampi (red arrows) which were nonenhancing.

**Figure 2. Heat Map Showing the CSF Host Transcriptional Profile of the Patient Compared With Profiles From Patients With Autoimmune Encephalitis or Bacterial Meningitis**
Normalized RNA expression levels, as arranged by unsupervised hierarchical clustering reflect gene overexpression (light green) and underexpression (dark blue). The asterisk denotes the column corresponding to the IL1R2 gene, which is overexpressed in the patient and bacterial meningitis samples relative to the autoimmune samples.

See this image and copyright information in PMC

References

1. Diprose W, Jordan A, Anderson NE. Autoinflammatory syndromes in neurology: when our first line of defence misbehaves. Prac Neurol. 2022;22:145-153. - PubMed
1. Bonnin AJ, Zeitz HJ, Gewurz A. Complement factor I deficiency with recurrent aseptic meningitis. Arch Intern Med. 1993;153(11):1380-1383. - PubMed
1. Haerynck F, Stordeur P, Vandewalle J, et al. . Complete factor I deficiency due to dysfunctional factor I with recurrent aseptic meningo-encephalitis. J Clin Immunol. 2013;33(8):1293-1301. - PubMed
1. Altmann T, Torvell M, Owens S, et al. . Complement factor I deficiency: a potentially treatable cause of fulminant cerebral inflammation. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e689. - PMC - PubMed
1. Karczewski KJ, Francioli LC, Tiao G, et al. . The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434-443. - PMC - PubMed

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Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report

Affiliations

Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous