@article{TEXTUAL,
      recid = {5872},
      author = {Root-Bernstein, Robert and Chiles, Kaylie and Huber, Jack  and Ziehl, Alison and Turke, Miah and Pietrowicz, Maja},
      title = {<i>Clostridia</i> and Enteroviruses as  Synergistic Triggers of Type 1 Diabetes Mellitus},
      journal = {International Journal of Molecular Sciences},
      address = {2023-05-06},
      number = {TEXTUAL},
      abstract = {What triggers type 1 diabetes mellitus (T1DM)? One common  assumption is that triggers are individual microbes that  mimic autoantibody targets such as insulin (INS). However,  most microbes highly associated with T1DM pathogenesis,  such as coxsackieviruses (COX), lack INS mimicry and have  failed to induce T1DM in animal models. Using proteomic  similarity search techniques, we found that COX actually  mimicked the INS receptor (INSR). Clostridia were the best  mimics of INS. Clostridia antibodies cross-reacted with INS  in ELISA experiments, confirming mimicry. COX antibodies  cross-reacted with INSR. Clostridia antibodies further  bound to COX antibodies as idiotype–anti-idiotype pairs  conserving INS–INSR complementarity. Ultraviolet  spectrometry studies demonstrated that INS-like Clostridia  peptides bound to INSR-like COX peptides. These  complementary peptides were also recognized as antigens by  T cell receptor sequences derived from T1DM patients.  Finally, most sera from T1DM patients bound strongly to  inactivated Clostridium sporogenes, while most sera from  healthy individuals did not; T1DM sera also exhibited  evidence of anti-idiotype antibodies against idiotypic INS,  glutamic acid decarboxylase, and protein tyrosine  phosphatase non-receptor (islet antigen-2) antibodies.  These results suggest that T1DM is triggered by combined  enterovirus-Clostridium (and possibly combined  Epstein–Barr-virus-Streptococcal) infections, and the  probable rate of such co-infections approximates the rate  of new T1DM diagnoses.},
      url = {http://knowledge.uchicago.edu/record/5872},
}