Affordable Access

Publisher Website

Pancreatic Duodenal Homeobox Protein 1 (Pdx1) Is a Novel β-Cell Specific Autoantigen for Type 1 Diabetes

Laboratory Investigation
Nature Publishing Group
Publication Date
DOI: 10.1038/labinvest.2009.116
  • Article
  • Biology
  • Medicine


Pdx1 is a key transcription factor involved in the regulation of insulin gene expression that is expressed at high levels in the β-cells of the pancreatic islets. We asked whether Pdx1 is a target of anti-islet autoimmunity in Type 1 diabetes (T1D). Pdx1 autoantibodies (PAA) were detected in non-obese diabetic (NOD) mice using ELISA, Western blotting, and radioimmunoprecipitation of [35S]-labeled insulinoma cell line-derived Pdx1 protein. PAA were detected as early as at 5 weeks of age, and generally peaked before the onset of clinically overt diabetes in diabetes-prone female NOD mice. Levels declined substantially after diabetes onset. PAA were not detected in the sera of NOD-scid, C57BL/6 or BALB/c mice. The titers of PAA in NOD mouse sera were as high as 1/93750 by ELISA. The fine specificity of PAA was determined by Western blotting using a series of truncated recombinant Pdx1 proteins. The immunodominant epitopes were located to the Pdx1 C-terminus (p200-283) in NOD mice. PAA also were detected in sera from human T1D patients, but the major epitopes were localized to amino acids 159-200 as well as the same region (p200-283) recognized by PAA from NOD mice. Using [3H]-thymidine incorporation, the p83 fragment of Pdx1 specifically stimulated proliferation of splenic T-cells from recent-onset diabetic NOD mice. The presence of PAA in prediabetic NOD mice and human T1D patients and Pdx1-specific T-cell proliferation in NOD mice provide a strong rationale for further investigation of the pathogenic role of immune responses against Pdx1 in T1D.

There are no comments yet on this publication. Be the first to share your thoughts.