The Type 1 Diabetes Signature: Hardwired to Trigger Inflammation?

According to a Vietnamese proverb, brothers and sisters are as close as hands and feet. This proverb is meant to describe siblings’ shared origin and resemblance yet also hints at their ability to act independently. Applied to type 1 diabetic (T1D) families, it appears that while an overactive immune system may be a common trait, each family member’s body tends to have a particular way of dealing with that imbalance. In this issue of Diabetes , Chen et al. (1) reveal that healthy T1D family members share a proinflammatory gene expression signature with their diabetic probands, regardless of HLA-associated risk or autoantibody status. Whether the observed inflammatory state progresses to overt disease, and at what pace, seems to depend on an individual’s ability to counteract inflammation.T1D is a polygenic autoimmune disease that is characterized by innate and adaptive immunity against β-cell components (2). Among the array of susceptibility genes, HLA-associated risk represents the lion’s share. It is widely acknowledged that environmental challenges are involved in genetically at-risk subjects’ progression toward autoantibody development and clinical onset (3). Monozygotic twins, for instance, show a significant degree of concordance in islet autoimmunity despite great temporal variation, suggesting a putative external trigger (4). At present, no therapy exists that can halt the immune-mediated destruction of β-cells. Some highly anticipated late-stage trials in recently diagnosed patients had disappointing results, most notably with anti-CD3 therapy (5). One reason may be that around the time of diagnosis—when most functional β-cell mass is destroyed—the …