Mast cell tryptases in allergic inflammation and immediate hypersensitivity

Dysregulated mast cell-mediated inflammation and/or activation have been linked to a number of human diseases, including asthma, anaphylaxis, chronic spontaneous urticaria, and mast cell activation syndromes. As a major mast cell granule protein, tryptase is a biomarker commonly used in clinical practice to diagnose mast cell-associated disorders and -mediated reactions, but its mechanistic roles in disease pathogenesis remains incompletely understood. Here, we summarize recent advances in the understanding of human tryptase genetics and the effects that different genetic composition may have on the quaternary structure of tetrameric mature tryptases. We also discuss how these differences may impact clinical phenotypes including allergic inflammation, immediate hypersensitivity, and others seen in patients with mast cell-associated disorders. With the increased application of next-generation sequencing, we foresee that human genetic approaches will be a major focus of understanding human tryptase functions in various human mast cell disorders and in new therapeutic development.

Automated summary

The dysregulated mast cell-mediated inflammation and activation are linked to various human diseases, and tryptase, a major mast cell granule protein, is commonly used as a biomarker for diagnosing mast cell disorders. However, the mechanistic roles of tryptase in disease pathogenesis are not fully understood. Studies on human tryptase genetics have shown that different genetic composition may impact the structure of tetrameric mature tryptases, leading to clinical phenotypes seen in patients with mast cell-associated disorders. With the advancement of next-generation sequencing, human genetic approaches will play a key role in understanding the functions of tryptase in mast cell disorders and in new therapeutic development.