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

Francesca Capasso, Novella Rapini, Gigliola Di Matteo, Manuela Testi, Susanna Arcano, Roberta Lidano, Arianna Petrelli, Paolo Rossi, Simona Piccinini, Maria Luisa Manca Bitti, Federica Angelini

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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.

Original languageEnglish
Pages (from-to)304-310
Number of pages7
JournalPediatric Diabetes
Volume14
Issue number4
DOIs
Publication statusPublished - Jun 2013

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Keywords

  • Autoimmune thyroid diseases
  • PTPN22
  • T cells
  • T1D
  • ZnT8 autoantibodies

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

Capasso, F., Rapini, N., Di Matteo, G., Testi, M., Arcano, S., Lidano, R., Petrelli, A., Rossi, P., Piccinini, S., Manca Bitti, M. L., & Angelini, F. (2013). A variable degree of autoimmunity in the pedigree of a patient with type 1 diabetes homozygous for the PTPN22 1858T variant. Pediatric Diabetes, 14(4), 304-310. https://doi.org/10.1111/j.1399-5448.2012.00891.x