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Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells

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Date
2019
Author(s)
Valta, Milla
Gazali, Ahmad Mahfuz
Viisanen, Tyyne
Ihantola, Emmi-Leena
Ekman, Ilse
Toppari, Jorma
Knip, Mikael
Veijola, Riitta
Ilonen, Jorma
Lempainen, Johanna
Kinnunen, Tuure
Unique identifier
10.1002/eji.201948378
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Citation
Valta, Milla. Gazali, Ahmad Mahfuz. Viisanen, Tyyne. Ihantola, Emmi-Leena. Ekman, Ilse. Toppari, Jorma. Knip, Mikael. Veijola, Riitta. Ilonen, Jorma. Lempainen, Johanna. Kinnunen, Tuure. (2019). Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells.  European journal of immunology, [Epub ahead of print 19 Dec 2019], 10.1002/eji.201948378.
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© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Abstract

Dysfunction of FOXP3‐positive regulatory T cells (Tregs) likely plays a major role in the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). Whether genetic polymorphisms associated with the risk of autoimmune diseases affect Treg frequency or function is currently unclear. Here, we analysed the effect of T1D‐associated major HLA class II haplotypes and seven single nucleotide polymorphisms in six non‐HLA genes [INS (rs689), PTPN22 (rs2476601), IL2RA (rs12722495 and rs2104286), PTPN2 (rs45450798), CTLA4 (rs3087243), and ERBB3 (rs2292239)] on peripheral blood Treg frequencies. These were determined by flow cytometry in 65 subjects who had progressed to T1D, 86 islet autoantibody‐positive at‐risk subjects, and 215 islet autoantibody‐negative healthy controls. The PTPN22 rs2476601 risk allele A was associated with an increase in total (p = 6 × 10−6) and naïve (p = 4 × 10−5) CD4+CD25+CD127lowFOXP3+ Treg frequencies. These findings were validated in a separate cohort comprising ten trios of healthy islet autoantibody‐negative children carrying each of the three PTPN22 rs2476601 genotypes AA, AG, and GG (p = 0.005 for total and p = 0.03 for naïve Tregs, respectively). In conclusion, our analysis implicates the autoimmune PTPN22 rs2476601 risk allele A in controlling the frequency of Tregs in human peripheral blood.

Subjects
autoimmunity   human   PTPN22   regulatory T cells   type 1 diabetes   
URI
https://erepo.uef.fi/handle/123456789/7959
Link to the original item
http://dx.doi.org/10.1002/eji.201948378
Publisher
Wiley
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  • Terveystieteiden tiedekunta [1324]
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