Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C

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  • Nicole Hartwig Trier
  • Niccolo Valdarnini
  • Ilaria Fanelli
  • Paolo Rovero
  • Hansen, Paul Robert
  • Claus Schafer
  • Evaldas Ciplys
  • Rimantas Slibinskas
  • Flemming Pociot
  • Tina Friis
  • Gunnar Houen
Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D. In addition, coxsackievirus B4 (CVB4) has previously been proposed to be involved in the onset of T1D through molecular mimicry. On this basis, we aimed to examine antibody cross-reactivity between a specific region of GAD65 and GAD67, which has high sequence homology to the nonstructural P2C protein of CVB4 to determine potential correlations at antibody level. Monoclonal peptide antibodies generated in mice specific for a region with high similarity in all three proteins were screened for reactivity along with human sera in immunoassays. In total, six antibodies were generated. Two of the antibodies reacted to both GAD isoforms. However, none of the antibodies were cross-reactive to CVB, suggesting that antibody cross-reactivity between GAD65 and CVB, and GAD67 and CVB may not contribute to the onset of T1D and SPS, respectively.
Original languageEnglish
Article number4424
JournalInternational Journal of Molecular Sciences
Issue number8
Number of pages16
Publication statusPublished - 2022

ID: 300081654