Allergies affect over one third of the world's population, and the prevalence of asthma is estimated at 300 million patients worldwide 17. In the US alone, asthma prevalence is 8-10% with a subset of 10% who suffer from severe disease. Allergen-specific IgE is a major mediator of severe allergic conditions and asthma exacerbations, but little is understood about the biology of human IgE in these patients. The presence of human IgE long-lived plasma cells is a matter of controversy, since mouse models show little evidence of IgE BM resident plasma cells fueling debate that IgE levels are maintained only by ongoing replenishment from short-lived ASC. In my laboratory, we have identified a new LLPC subset in the human bone marrow (BM) compartment and characterized 5 novel circulating ASC populations. In this application, we will demonstrate the presence of human IgE BM LLPC in allergic patients and understand the cellular origins of allergen-specific IgE responses during acute recall responses (after natural allergen exposures) in blood, bone marrow and nasal polyps.
Asthma and allergies affects 300 million worldwide and 60 million Americans with US annual cost of asthma estimated to be near $18 billion. Within that number, 25 million people suffering from asthma (8% in adults, 9% in children) and approximately 60% are due to 'allergic asthma'. For many who suffer from allergies and allergic asthma, IgE is a main mediator of disease, but little is understood about the cellular origins of human IgE; therefore this application will characterize the cellular origins of IgE which will likey lead to new targets for novel immune therapeutic approaches and/or rational new indications for already FDA approved immune biologics.
|Halliley, Jessica L; Tipton, Christopher M; Liesveld, Jane et al. (2015) Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity 43:132-45|