Transcriptional signals of increased IgA- and IgG-producing plasma cell activity, together with eosinophil-specific hypermethylation patterns and unresponsiveness to IgE blockade, point to immunoglobulin-mediated mechanisms that contribute to asthma pathogenesis independently of classical T2 cellular pathways, yet within a persistent T2 inflammatory milieu. Here, IGHE is linked to asthma.