Effects beyond the late phase
The detected amounts of IL-8, IL-13 and LIF are still significantly different from baseline 24 hours after allergen activation (p < 0.001) (figure 2, a-c). This could indicate an effect of these cytokines that goes beyond the late phase response (6-8 hours) and possibly adds to the development of chronic inflammation. Increased cytokine secretion may be associated with asthma severity as is supported by studies showing higher levels of IL-8 and IL-13 in patients with chronic severe asthmatic disease in addition to a negative correlation of cytokine secretion with lung function (20,30,31) . Several cytokines novel to the mast cell were also significantly upregulated by high affinity IgE (CSF-1, FLT3L, HGF, OSM and IL-12b). CSF-1 and Flt3L may be involved in maintenance and activation of hematopoietic progenitors, and HGF supports angiogenesis and tissue regeneration of epithelial cells. OSM remains poorly defined, but closely related to IL-6 and LIF.
When combining the current results with data from animal models(1,2) mast cells seem to be able to sense differences in IgE affinity and this may have important implications for their role in shaping early and late phase allergic responses and may even impact chronic asthma by bridging between different endotypes dominated by immune cell subsets favored by different mast cell mediators. Clearly, additional experiments are needed to substantiate the direct effects of molecular editing through kinetic proofreading in human as well as mouse mast cells and its downstream effects. Moreover, links between IgE affinity and asthma endotypes may be followed up in allergic individuals with primarily high vs low affinity IgE towards well characterized allergens.