Theo Gulen

I am an Associate Professor of Allergy at Karolinska Institutet and a board‑certified physician in Internal Medicine, Clinical Immunology, and Allergology. I currently serve as a Senior Consultant at the Respiratory Diseases and Allergy Clinic, Karolinska University Hospital in Stockholm. My clinical and academic work is centred on anaphylaxis, systemic mastocytosis, mast‑cell activation disorders, hereditary alpha‑tryptasemia, and other complex hypersensitivity conditions. I earned my PhD at Karolinska Institutet in 2014, focusing on the relationship between mastocytosis and anaphylaxis—an area that has continued to shape my clinical and scientific trajectory.

Over more than 20 years of clinical leadership at the Karolinska ECNM Mastocytosis Center, I have investigated and managed a clinical cohort of more than 900 patients with systemic mastocytosis, MCAS, and hereditary alpha‑tryptasemia, from which I have curated a unique local registry that underpins several of our translational and clinical research studies.

I have also delivered over 200 lectures at universities, national symposia, and international ECNM/EAACI/AIM meetings to specialists, trainees, and patient communities.

ANAPHYLAXIS, MCAS AND SYSTEMIC MASTOCYTOSIS: DISORDERS MANIFESTING WITH MAST CELL ACTIVATION

My research focuses on understanding the mechanisms underlying systemic mast‑cell activation and the clinical heterogeneity observed across mast‑cell disorders. A central aim is to characterize distinct clinical phenotypes and biological endotypes in patients with severe anaphylaxis, Mast Cell Activation Syndrome (MCAS), and systemic mastocytosis (SM). This work integrates detailed clinical phenotyping with proteomic profiling and mast‑cell functional studies to identify biomarkers that reflect mast‑cell hyperreactivity and dysregulated activation pathways.

A key component of my current research is the investigation of mast‑cell activation biomarkers in plasma and urine, combined with cellular assays that assess mast‑cell releasability and effector responses. Patients with SM and other mast‑cell activation disorders provide a clinically relevant model for studying severe, recurrent anaphylaxis. Ongoing projects therefore focus on defining diagnostic and prognostic biomarker signatures within these patient groups. Through this approach, we aim to delineate biological mechanisms that drive heightened mast‑cell reactivity and to identify endotypes associated with severe clinical manifestations.

By integrating clinical, proteomic, and functional data, this research seeks to improve the prediction of patients at risk for severe, recurrent anaphylaxis and to support the development of more personalized diagnostic and therapeutic strategies for mastocytosis, MCAS, and other mast‑cell–related conditions. Incorporating hereditary alpha‑tryptasemia as a genetic trait provides an opportunity to explore whether germline variation in TPSAB1 copy number relates to particular clinical presentations, without assuming a direct mechanistic effect on mast‑cell reactivity.

Ultimately, understanding these regulatory mechanisms may help identify patients at risk for severe, recurrent anaphylaxis and guide the development of individualized treatment strategies for mastocytosis and other mast‑cell disorders, including severe allergic disease.

My previous work has focused on defining diagnostic criteria for MCAS, clarifying the true prevalence of MCAS in allergy practice, and improving the diagnosis and management of anaphylaxis in SM and other mast‑cell disorders (MCDs). I am also actively involved in ECNM, AIM, EAACI, WAO, and Nordic expert initiatives on mastocytosis and MCDs/MCAS, contributing to international efforts to refine classification, harmonize diagnostic standards, and advance clinical practice. 

Featured Publications:

Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review.  

Gülen T, Akin C, Bonadonna P, et al. JACI In Practice, 2021.

→ Role & Impact: First author contributing to the initiation and development of a widely cited diagnostic framework for MCAS in allergy and clinical immunology, clarifying how established criteria should be applied in practice to avoid overdiagnosis and improve clinical accuracy.

→ Co‑author of a review examining the clinical relevance of hereditary alpha‑tryptasemia in mastocytosis and other mast‑cell disorders, highlighting knowledge gaps and future research priorities.

→ Scientific and manuscript lead for a two‑cohort study demonstrating that drug‑induced anaphylaxis is uncommon in systemic mastocytosis, providing evidence to guide risk assessment and clinical decision‑making in drug allergy evaluation.

A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis.

→ Sole author of a conceptual review integrating the clinical and biological relationships between anaphylaxis, MCAS, and mastocytosis, offering a unified framework for understanding overlapping mast‑cell activation disorders.

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium.

Valent P, Hartmann K, Bonadonna P,  Gülen T, et al. JACI In Practice, 2022.  

→ Contributing member of an international expert consortium proposing a unified classification system for mast‑cell activation disorders, aligning diagnostic terminology with ICD‑10‑CM and supporting global standardization.

Clinical Outcomes of Adults with Systemic Mastocytosis: A 15-Year Multidisciplinary Experience.

→ Senior author of a long‑term multidisciplinary outcomes study providing real‑world data on disease course, treatment patterns, and prognostic factors in systemic mastocytosis across a 15‑year cohort.

Anaphylaxis and Mast Cell Disorders.

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

I have been actively involved in medical education at Karolinska Institutet across graduate, postgraduate, and professional levels. My teaching focuses on allergic disorders—including anaphylaxis, mastocytosis, MCAS and other mast‑cell diseases, asthma, and immunological mechanisms underlying allergic conditions.

Overall, I have delivered more than 200 lectures at universities, national symposia, and international ECNM/EAACI/AIM conferences to specialists, residents, medical students, nurses, and patient groups.

At the undergraduate level, I teach third‑year medical students through lectures, problem‑based learning sessions, and direct clinical tutorship at the Departments of Medicine in Solna and Huddinge. These activities include both theoretical instruction and bedside clinical teaching.

I serve as the Director of Postgraduate Training for Allergy Residents/Fellows at Karolinska University Hospital, a role that involves planning, coordinating, and ensuring the quality of specialist training in Allergology. In addition, I regularly teach residents and specialists in Internal Medicine, Allergy, and Pulmonology, as well as general practitioners and doctoral students, on a broad range of allergic diseases.

I am also co‑organiser of the national biannual Advanced Allergology Courses, which attract both paediatric and adult allergy residents and fellows from across Sweden and contribute to strengthening specialist education. 

My supervisory activities include mentoring PhD candidates and medical students, guiding research projects focused on mast cell–mediator-related disorders, and anaphylaxis, and supporting the academic development of trainees at Karolinska Institutet and Karolinska University Hospital.

*PhD supervisor*
On-going >> Principal supervisor for Ilia Brooke.

*Completed*
Jennine Grootens, PhD 2019, KI, Co-supervisor