Development of a T1D-Specific Biomarker of Early Autoimmunity

Autoimmunity and beta cell destruction occur without symptoms for months to years before the onset of T1D is clinically recognized, providing an excellent opportunity for earlier diagnosis and intervention. However, early signs of the autoimmune process in people at risk of T1D is very difficult to directly measure in the circulating blood. Therefore, work is ongoing to develop more sensitive measurements of early autoimmune signals suitable for studies of the T1D disease processes, for earlier diagnosis, to help guide therapeutic decisions, and for monitoring disease interventions. These investigators previously demonstrated that plasma (a component of blood) from recent-onset T1D patients’ can trigger a signature panel of gene expression in these cells. This signature is absent in unrelated healthy controls. In this study, the authors further fine-tuned their discovery over the natural course of the disease to establish the presence of this T1D signature as early as 5 years prior to disease diagnosis. Importantly, these studies also validate a key consideration in the area of T1D immune biomarker research – the capacity of previously frozen blood cells to serve as disease-specific biosensors. A limitation in past studies that have utilized cell-based assays, has been the reliance on freshly isolated blood cells for accurate read-outs. This study shows that frozen cells are equally capable of sensitively and comprehensively capturing the perturbations of the immune system and differentiating the diverse range of immune-mediated processes that underlie this disease. Additional studies are needed to more rigorously determine that these findings are specific to T1D autoimmunity.

Ramifications for Individuals with T1D:

As predictors of disease, auto-antibodies are thought to appear late during pre-diabetes, their levels can be transient, and not all auto-antibody positive subjects progress to T1D onset. Thus, a need remains for the discovery and evaluation of minimally invasive biomarkers that are reliable, T1D-specific, and capable of detecting early signs of the autoimmune process in T1D.

JDRF Involvement:

This work was funded in part by JDRF.

Investigators and Institutions:

This work was led by Dr. Marty Hessner at the Medical College of Wisconsin.

Reference:

Levy H, Wang X, Kaldunski M, Jia S, Kramer J, Pavletich SJ, Reske M, Gessel T, Yassai M, Quasney MW, Dahmer MK, Gorski J, Hessner MJ. (2012) Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun. 13(8):593-604 (Epub 2012 Sep 13).