Tu79 - Searching for Environmental Triggers of Juvenile Dermatomyositis Using Antibody Profiling Technology

Background: Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune muscle diseases characterized by chronic progressive muscle weakness. The causes of these autoimmune myopathies are unknown. The prevailing hypothesis is that environmental triggers can precipitate disease in individuals with genetic susceptibility. Antibody profiling can serve as an unbiased method of characterizing environmental exposures.

Methods: We used Phage ImmunoPrecipitation Sequencing (PhIP-Seq) with a library that covers all known protein toxin and virulence factors (“ToxScan”), to identify environmental IgG antibody reactivities in IIM patients. Candidate antigens were identified via comparison of IIM groups (cases) to controls using a case-control analysis software. The most significant reactivity in cases compared to controls was validated using Mesoscale Diagnostics (MSD).

Results: PhIP-Seq with the ToxScan library identified increased anti-flagellin antibodies in juvenile dermatomyositis (JDM). The anti-flagellin antibodies displayed reactivity to several flagellin peptides from various bacterial species with conserved epitopes. Increased flagellin reactivity in JDM patients, compared to age-matched controls (including sibling and twin controls), was validated by MSD. Additionally, flagellin reactivity in JDM patients is associated with an age of 10 years or younger.

Conclusions and Next Steps: Profiling antibody reactivities targeting environmental antigens can be used to identify triggers of autoimmune diseases, such as IIMs. Ongoing studies will use PhIP-Seq to determine IgA reactivities in JDM flagellin-positive patients. Ultimately, this work will deepen our understanding of the complex interplay between the microbiota, host immunity, and the development of JDM and other IIMs.