Diseases associated with mast cells: current state of the problem

Abstract

Mast cells (MCs), originating from hematopoietic stem cells, play a pivotal role in the development of numerous allergic and non-allergic diseases. Upon interaction with allergens, they become activated, leading to degranulation and the release of various inflammatory mediators that initiate an acute inflammatory response. Beyond allergopathology, MCs are implicated in the pathogenesis of a broad spectrum of conditions, including malignancies, arthritis, ischemic heart disease, osteoporosis, and other chronic inflammatory or systemic conditions. In recent years, our understanding of the role of MCs and disorders linked to their dysfunction has deepened significantly. It has been established that some of these conditions have a genetic basis, notably the KIT D816V mutation, which enhances MC functional activity and is associated with clonal diseases such as cutaneous and systemic astocytosis (including indolent, smoldering, and aggressive forms) as well as syndromes of clonal or monoclonal MC activation. Additionally, MC activation can be secondary, occurring in response to allergic, inflammatory, or paraneoplastic processes. In certain cases, the mechanisms of this activation remain unclear, classifying these conditions as idiopathic. Furthermore, there exists a hereditary genetic syndrome — hereditary alpha-tryptasemia (HαT) – which increases the severity of allergic and anaphylactic reactions and may coexist with both clonal and non-clonal MC disorders, forming complex hybrid clinical manifestations. The aim of this publication was to analyze existing data from scientific literature on MCs associated diseases. We aimed to detail the contemporary classification of these disorders, highlight relevant genetic defects, and outline diagnostic and targeted therapy approaches that may improve the management of affected patients.