Theo Gulen

ALLERGY, ANAPHYLAXIS AND MASTOCYTOSIS: DISORDERS MANIFESTING WITH MAST CELL ACTIVATION

My current research is dedicated to elucidating the underlying mechanisms driving systemic mast cell activation and its associated clinical manifestations. This investigation focuses on characterizing the distinct clinical and biological phenotypes observed in individuals diagnosed with Mast Cell Activation Disorders (MCAD), including severe anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis. A central aim of this work is to identify reliable biomarkers indicative of mast cell hyperreactivity and to define discrete endotypes within this heterogeneous patient population. By dissecting the molecular and cellular pathways that contribute to the intrinsic hyperresponsiveness and enhanced releasability of mast cells, this research seeks to uncover the primary perturbations responsible for the severe and dysregulated activation observed in affected individuals. 

Anaphylaxis is a rapidly developing and serious hypersensitivity reaction that can concurrently affect multiple organ systems. It remains as a clinical entity and the diagnosis is based on constellation of different signs and symptoms according to the World Allergy Organization (WAO) diagnostic criteria, which involves two or more organs including skin/mucosal membranes, airways, cardiovascular, and/or gastrointestinal systems. These criteria enabled clinicians across the world to 'speak the same language' and facilitated tremendously patients and acute care physician to recognize and treat it promptly. It also made possible for scientist to report meaningful, comparable data. However, despite significant progresses in allergology and immunology during the last 2-3 decades, understanding of anaphylaxis for an allergist is fairly limited at present with respect to factors determining severity, underlying intracellular effector mechanisms within mast cells, co-factor influence, and immune mechanisms involving in mast cell activation syndromes (MCAS) and disorders (MCAD).

To investigate this, future studies should approach anaphylaxis in a concerted manner with detailed phenotyping/endotyping by exploring the role of mast cell activation biomarkers in plasma and urine. In this context, patients with MCAD, such as mastocytosis are of great relevance to study patients with severe anaphylaxis, as these patients usually develop recurrent, severe anaphylaxis. Therefore, the main focus of the current project will be exploring clinical and biological features of MCAD patients to better understand mechanisms of anaphylaxis by screening specific diagnostic and prognostic biomarkers in patients with mastocytosis. We also aim to identify novel biomarkers of severe anaphylaxis.

Ultimately, understanding these regulatory mechanisms might help to predict patients with severe anaphylaxis as well as to develop personalized treatment options for individual patients with mastocytosis and other mast cell disorders, such as severe allergies.

LINK: https://pubmed.ncbi.nlm.nih.gov/?term=gulen%20t&sort=date