Clinical and Pathophysiological Tangles Between Allergy and Autoimmunity: Deconstructing an Old Dichotomic Paradigm

Allergic and autoimmune disorders are characterised by dysregulation of the immune responses to otherwise inert environmental substances and autoantigens, leading to inflammation and tissue damage. Their incidence has constantly increased in the last decades, and their co-occurrence defies current standards in patient care. For years, allergy and autoimmunity have been considered opposite conditions, with IgE and Th2 lymphocytes cascade driving canonical allergic manifestations and Th1/Th17-related pathways accounting for autoimmunity. Conversely, growing evidence suggests that these conditions not only share some common inciting triggers but also are subtended by overlapping pathogenic pathways. Permissive genetic backgrounds, along with epithelial barrier damage and changes in the microbiome, are now appreciated as common risk factors for both allergy and autoimmunity. Eosinophils and mast cells, along with autoreactive IgE, are emerging players in triggering and sustaining autoimmunity, while pharmacological modulation of B cells and Th17 responses has provided novel clues to the pathophysiology of allergy. By combining clinical and therapeutic evidence with data from mechanistic studies, this review provides a state-of-the-art update on the complex interplay between allergy and autoimmunity, deconstructing old dichotomic paradigms and offering potential clues for future research.