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Exploring Autoimmunity in a Cohort of Children with Genetically Confirmed Aicardi–Goutières Syndrome

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Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to explore the presence of autoimmune manifestations and characterize the autoantibody production in a cohort of patients with Aicardi–Goutières syndrome (AGS).

Methods

Seventeen patients with a genetically-confirmed diagnosis of AGS were recruited. At the time of enrollment, past medical and family history was reviewed, looking for possible signs or symptoms of autoimmune disorders. Blood samples were taken, for the detection of a panel of autoantibodies: anti-nuclear, anti-double-stranded-DNA, anti-nucleosome, anti-extractable nuclear antigens, anti-cardiolipin IgG/IgM, anti-β2glycoprotein I IgG/IgM, and anti-neutrophil cytoplasmic. We also measured complement levels determined as C3 and C4 quantification and total complement activity, measured as CH50.

Results

Nine of seventeen patients presented with at least one first- or second-degree relative with a history of autoimmune diseases (the childrens’ mother or grand-mother in the majority of cases). A specific autoimmune disease was present in only one AGS patient, namely an autoimmune thyroiditis. Autoantibodies were present in 9/17 patients, with different patterns of positivity. Complement levels were normal in all the patients. There was no correlation between auto-antibody production and personal or family history of autoimmune diseases.

Conclusions

Definite autoimmune diseases are not common in patients with AGS. Autoantibodies are mainly directed towards nucleic acids-containing elements but seem not to be pathogenic and, rather, may represent an epiphenomenon of the enhanced interferon production.

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Abbreviations

CSF:

Cerebrospinal fluid

CNS:

Central nervous system

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Acknowledgments

The authors would like to thank Prof. Yanick Crow and Dr. Gillian Rice for performing genetic analysis in most of the patients included in this work and Prof. Crow for critically reviewing the manuscript.

Authorship Contributions

M.C., J.C., L.A., E.F, A.T., and S.O. designed the study. M.C., J.C., E.F, S.O., and I.O. recruited and evaluated the patients. L.A., M.F., G.A., and A.T. performed the laboratory tests. M.C., J.G., and L.A. wrote the manuscript. E.F., A.T., and S.O. reviewed the manuscript. M.C. coordinated the study and the manuscript preparation. The IAGSA study group is a group of physicians and biologists from the Spedali Civili di Brescia and from the Mondino Institute in Pavia, dedicated to the care of patients with AGS and to foster research in the field. All the IAGSA study group members participated in different phases of the study and reviewed the manuscript before submission.

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Authors and Affiliations

  1. Pediatric Clinic, Spedali Civili di Brescia, Brescia, Italy

    Marco Cattalini

  2. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Marco Cattalini, Laura Andreoli, Angela Tincani & Elisa Fazzi

  3. Child Neurology and Psychiatry Unit, Spedali Civili di Brescia, Brescia, Italy

    Jessica Galli & Elisa Fazzi

  4. Department of Clinical Immunology and Rheumatology, Spedali Civili di Brescia, Brescia, Italy

    Jessica Galli, Laura Andreoli, Micaela Fredi & Angela Tincani

  5. Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy

    Ivana Olivieri, Giada Ariaudo & Simona Orcesi

  6. Don Carlo Gnocchi ONLUS Foundation, Milan, Italy

    Ivana Olivieri

  7. Department of Brain and Behavioural Sciences, Child Neurology and Psychiatry Unit, University of Pavia, Pavia, Italy

    Giada Ariaudo

Authors
  1. Marco Cattalini
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  2. Jessica Galli
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  3. Laura Andreoli
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  4. Ivana Olivieri
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  5. Giada Ariaudo
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  6. Micaela Fredi
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  7. Simona Orcesi
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  8. Angela Tincani
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  9. Elisa Fazzi
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IAGSA study group

Corresponding author

Correspondence to Marco Cattalini.

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Funding

Part of this work was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) (S.O.); CARIPLO Foundation (E.F.) and Regione Lombardia (E.F.).

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

All coauthors have reviewed the manuscript and have contributed in a substantive and intellectual manner to the work described.

F. Bettera, M. Bianchi, N. Carabellese, M. De Simone, R. Ferraro, F. Gavazzi, S. Giliani, G. Gualdi, A. Meini, I. Parissenti, D. Vairo, A. Zanola were members of IAGSA study group.

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Cattalini, M., Galli, J., Andreoli, L. et al. Exploring Autoimmunity in a Cohort of Children with Genetically Confirmed Aicardi–Goutières Syndrome. J Clin Immunol 36, 693–699 (2016). https://doi.org/10.1007/s10875-016-0325-y

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  • DOI: https://doi.org/10.1007/s10875-016-0325-y

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