Assessing IgE and basophil activity in blood samples from nonhuman primates

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Assessing IgE and basophil activity in blood samples from nonhuman primatesTo the Editor, The dramatic rise in the prevalence of allergies observed in recent decades requires developing and testing new drugs to fight this major public health problem.Nonhuman primates (NHPs) such as cynomolgus monkeys (Macaca fascicularis) are often used in preclinical drug development for dose-range finding studies, and to assess the safety of new pharmaceuticals prior to initiation of clinical trials.IgE antibodies play a key role in allergic diseases, as best exemplified by the efficacy of the anti-IgE Omalizumab in allergic asthma. 1 However, the extent to which NHP IgE biology reflects that of human is not fully understood, and further knowledge on this is required to ensure clinical relevance of toxicological and functional studies of novel therapies targeting IgE.We performed a sequence alignment of the heavy chain constant region (Cε1-4) of human and cynomolgus IgE, which revealed 84.3% identity and 91.6% similarity (Figure S1).Seven putative N-linked glycosylation sites have been described in human IgE heavy chain.Among these, N394-linked oligomannose glycans in the Cε3 domain are required for binding to the high-affinity IgE receptor FcεRI, and sialylations at several sites fine-tune IgE biological activity.2 Interestingly, all these putative N-linked glycosylation sites are conserved in cynomolgus with the exception of N383, which was found to be unoccupied by glycans in human IgE in a recent study 2 (Figure S1).Human IgE binds to the alpha chain of FcεRI through contacts with distinct epitopes forming surface loops in Cε3 and in the Cε2-Cε3 linker region, 3 all of which are conserved in cynomolgus

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