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A variable degree of autoimmunity in the pedigree of a patient with type 1 diabetes homozygous for the PTPN22 1858T variant

Authors

  • Francesca Capasso,

    1. Division of Pediatrics, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy
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  • Novella Rapini,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
    2. Department of Pediatrics, University of Rome Tor Vergata, Children's Hospital Bambino Gesù, Rome, Italy
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    • These authors contributed equally to this work.

  • Gigliola Di Matteo,

    1. Division of Pediatrics, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy
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    • These authors contributed equally to this work.

  • Manuela Testi,

    1. Laboratory of Immunogenetics, IME Foundation, Policlinico di Tor Vergata, Rome, Italy
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  • Susanna Arcano,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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  • Roberta Lidano,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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  • Arianna Petrelli,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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  • Paolo Rossi,

    1. Department of Pediatrics, University of Rome Tor Vergata, Children's Hospital Bambino Gesù, Rome, Italy
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  • Simona Piccinini,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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  • Maria Luisa Manca Bitti,

    1. Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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  • Federica Angelini

    Corresponding author
    • Division of Pediatrics, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy
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    • Current address: Unité d'Immuno-allergologie et Rhumatologie, Département de Pédiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.


Corresponding author:

Federica Angelini, MD, PhD,

Division of Pediatrics,

Department of Public Health and Cell Biology,

University of Rome Tor Vergata,

Via Montpellier 1,

00133 Rome,

Italy.

Tel: +41 21 314 33 24;

fax: +41 21 314 35 58;

e-mail: Federica.Angelini@chuv.ch

Abstract

We investigated whether the PTPN22 C1858T polymorphism is associated with the autoimmune conditions present in the family of a child affected by type 1 diabetes (T1D) carrying the TT genotype (index patient) and the potential immunological effect of the variant. We found that nine family members carried the CT genotype and five suffered from autoimmunity. Interestingly, anti-ZnT8 antibodies were detected in T1D patients and in three healthy relatives. In the TT patient, we showed diminished T-cell proliferation and reduced interleukin-2 (IL-2) and interferon-gamma (IFN-γ) production. A marked reduction of IL-2 was also observed for all CT relatives with autoimmunity and a lack of IFN-γ production was observed for the younger brother of the index patient, heterozygous for the polymorphism. In this family, the C1858T variant might confer a high risk of autoimmunity. Moreover, our data confirm that impaired IL-2 production upon T-cell receptor stimulation is associated with autoimmunity in the carriers of the polymorphism. This study might prompt to extend the panel of risk markers in relatives of subjects affected by T1D.

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