A variable degree of autoimmunity in the pedigree of a patient with type 1 diabetes homozygous for the PTPN22 1858T variant.
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.
Division of Pediatrics, Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00133, Rome, Italy.
Francesca
F
Capasso
Novella
N
Rapini
Gigliola
G
Di Matteo
Manuela
M
Testi
Susanna
S
Arcano
Roberta
R
Lidano
Arianna
A
Petrelli
Paolo
P
Rossi
Simona
S
Piccinini
Maria Luisa
ML
Manca Bitti
Federica
F
Angelini
D015551:Autoimmunity / Q000235:genetics*; D027682:Cation Transport Proteins / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D010375:Pedigree; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D000075703:Zinc Transporter 8
D027682:Cation Transport Proteins; D059811:HLA-DRB1 Chains; D007376:Interleukin-2; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22