Potential Biomarkers in Subects at Risk for the Development of T1D

The innate immune system, the part of the immune system that is tasked with defending the host from infections in a non-specific manner, has been implicated in the T1D disease process. In this paper, the investigators analyzed innate immune responses in T1D autoantibody positive individuals and compared them to individuals without autoantibodies. The investigators found that two immune system pathways, one involving Interleukin-1b and one involving Interleukin-6 were altered in autoantibody positive individuals when stimulated by TLRs compared to autoantibody negative individuals. TLRs are responsible for recognizing pathogens and activating the innate immune system, including interleukins, which are signaling molecules within the innate immune system. Furthermore, they showed that autoantibody-positive subjects have lower levels of CXCL-10 in their blood. CXCL-10 is a protein which is involved in the immune response as well as in the suppression of beta-cell proliferation. These results suggest that altered innate immunity exists in individuals before disease onset. This suggests that innate immune pathways may be involved in T1D pathogenesis and that molecules and pathways involved in the innate immune system may be useful as biomarkers of T1D for at-risk individuals.

Reference:

Alkanani AK, Rewers M, Dong F, Waugh K, Gottlieb PA, Zipris D. Diabetes. 2012 Oct;61(10):2525-33. Epub 2012 Jun 29. Dysregulated Toll-Like Receptor-Induced Interleukin-1 Beta and Interleukin-6 Responses in Subjects at Risk for the Development of Type 1 Diabetes.

Investigators and Institutions:

This study was led by Dr. Danny Zipris at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver.

Ramifications for Individuals with Type 1 Diabetes:

This study suggests that individuals at-risk for developing T1D, namely those individuals who are autoantibody-positive for T1D antigens, have altered innate immune pathways before disease onset. While an interesting finding, longitudinal studies in individuals from the at-risk stage who progress to overt T1D will needed to be evaluated to confirm and evaluate the potential involvement of the innate immune system in T1D pathogenesis. If the role of the innate immune system is confirmed, the innate immune system could be a potential target for therapeutics as well as for biomarkers for monitoring disease progression.

JDRF Involvement:

This study was funded by JDRF through grants to Dr. Danny Zipris.