Karger Publishers, International Archives of Allergy and Immunology, 3(166), p. 189-198, 2015
DOI: 10.1159/000380853
Full text: Download
<b><i>Background:</i></b> The protein tyrosine phosphatase nonreceptor type 22 <i>(PTPN22)</i> gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable <i>PTPN22</i> single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. <b><i>Methods:</i></b> We addressed the links between the functional and geographically variable <i>PTPN22 </i>SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). <b><i>Results:</i></b> The frequency of <i>PTPN22</i> polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α <i>(HNF1A)</i> MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. <b><i>Conclusions:</i></b> MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated <i>PTPN22</i> alleles. The absence of autoimmunity-associated <i>PTPN22</i> alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders.