Abstract Text: There are currently an estimated 476,000 cases of Lyme disease annually in the US, caused by the bacteria Borrelia burgdorferi (Bb). At least 10% of people with Lyme disease experience persistent symptoms after antibiotic treatment. Currently, there are no tools to predict Lyme disease illness trajectories; a significant barrier to research progress. While there historically has been a significant focus in the field on using bulk IgG and IgM antibodies to diagnose Lyme, we quantified all the different IgG subtypes, IgE, and IgA isotypes of antibodies. We found that the plasma of acute Lyme patients who went on to fully recover after antibiotics contained opposite levels of subtypes and isotypes than patients who developed persistent symptoms. We identified a novel protective immune profiling ratio of the different antibody types in patients who went on to recover. To further explore this, we developed a new FLow-based Immune Profiling technology (FLIP) to better profile Bb-specific antibody isotypes and subtypes. The FLIP innovatively uses live Bb as bait to precipitate out pathogen specific antibodies. We found sex differences in the levels and kinetics of certain Bb-specific antibody isotypes, including IgE. This is important because we found concerningly high levels of IgE that binds to Bb in a third of people experiencing persistent symptoms. In mice this IgE triggers mast cell degranulation. This could indicate the development of an allergy type response to Bb or parts of Bb that are also found in other bacteria, and point to treatment options used for allergies.
