Theo Gulen

About me

I am specialist physician in Internal Medicine, Clinical Immunology and Allergology and currently serve as a Senior Consultant in the Respiratory Diseases and Allergy Clinic, Karolinska University Hospital, Huddinge. I received my PhD from the Karolinska Institutet in 2014 in Allergy on a project dealing with Clonal Mast Cell Disorders (Mastocytosis) and Anaphylactic reactions.

Research description

Allergy, Anaphylaxis and Mastocytosis: Disorders Manifesting with Mast Cell Activation 

My current research aims to gain deeper insights in the mechanisms behind systemic mast cell activation by exploring distinct clinical and biological features of patients with “Mast Cell Activation Disorders”, such as patients with severe anaphylaxis, MCAS and mastocytosis. Moreover, I also focus on identifying biomarkers of hyperreactivity and endotypes, as inherently increased reactivity and releasability of mast cells leading to severe, uncontrolled mast cell activation appears to be the main perturbation in these patients. 

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 achieve 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.

Selected publications

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

Ungerstedt J, Ljung C, Klimkowska M, Gülen T. 

Cancers (Basel). 2022 Aug 16;14(16):3942. doi: 10.3390/cancers14163942.

-  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, Brockow K, Alvarez-Twose I, Hermine O, Niedoszytko M, Carter MC, Hoermann G, Butterfield JH, Lyons JJ, Sperr WR, Greiner G, Sotlar K, Kluin-Nelemans HC, Schwaab J, Lange M, George TI, Siebenhaar F, Broesby-Olsen S, Jawhar M, Nedoszytko B, Castells M, Orfao A, Gotlib J, Reiter A, Horny HP, Triggiani M, Arock M, Metcalfe DD, Akin C.

J Allergy Clin Immunol Pract. 2022 Aug;10(8):1941-1950. doi: 10.1016/j.jaip.2022.05.007. 

- COVID-19 vaccination in the setting of mastocytosis-Pfizer-BioNTech mRNA vaccine is safe and well tolerated.

Lazarinis N, Bossios A, Gülen T.

J Allergy Clin Immunol Pract. 2022 May;10(5):1377-1379. doi: 10.1016/j.jaip.2022.01.037. 

- Anaphylaxis and Mast Cell Disorders.

Gülen T, Akin C.

Immunol Allergy Clin North Am. 2022 Feb;42(1):45-63. doi: 10.1016/j.iac.2021.09.007.

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

Gülen T, Akin C, Bonadonna P, Siebenhaar F, Broesby-Olsen S, Brockow K, Niedoszytko M, Nedoszytko B, Oude Elberink HNG, Butterfield JH, Sperr WR, Alvarez-Twose I, Horny HP, Sotlar K, Schwaab J, Jawhar M, Zanotti R, Nilsson G, Lyons JJ, Carter MC, George TI, Hermine O, Gotlib J, Orfao A, Triggiani M, Reiter A, Hartmann K, Castells M, Arock M, Schwartz LB, Metcalfe DD, Valent P.J Allergy Clin Immunol Pract. 2021 Jun 22:S2213-2198(21)00676-0. doi: 10.1016/j.jaip.2021.06.011. Online ahead of print.PMID: 34166845 Free article.

- COVID-19 Vaccination in Mastocytosis: Recommendations of the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM).

Bonadonna P, Brockow K, Niedoszytko M, Elberink HO, Akin C, Nedoszytko B, Butterfield JH, Alvarez-Twose I, Sotlar K, Schwaab J, Jawhar M, Castells M, Sperr WR, Hermine O, Gotlib J, Zanotti R, Reiter A, Broesby-Olsen S, Bindslev-Jensen C, Schwartz LB, Horny HP, Radia D, Triggiani M, Sabato V, Carter MC, Siebenhaar F, Orfao A, Grattan C, Metcalfe DD, Arock M, Gulen T, Hartmann K, Valent P.J Allergy Clin Immunol Pract. 2021 Jun;9(6):2139-2144. doi: 10.1016/j.jaip.2021.03.041. Epub 2021 Apr 5.PMID: 33831618 

- Distinct plasma biomarkers confirm the diagnosis of mastocytosis and identify increased risk of anaphylaxis.

Gülen T, Teufelberger A, Ekoff M, Westerberg CM, Lyberg K, Dahlén SE, Dahlén B, Nilsson G. The Journal of allergy and clinical immunology 2021:346-348.

- Idiopathic Anaphylaxis: a Perplexing Diagnostic Challenge for Allergists.

Gulen T, Akin C. Curr Allergy Asthma Rep 2021:21(2):11.

- Low Frequency of IgE-Mediated Food Hypersensitivity in Mastocytosis.

Jarkvist J, Brockow K, Gülen T. J Allergy Clin Immunol Pract 2020:8(9):3093-3101.

- Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection.

Jarkvist J, Salehi C, Akin C, Gülen T. Allergy 2020:75(1):169-177.

- Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis.

Gülen T, Ljung C, Nilsson G, Akin C. J Allergy Clin Immunol Pract 2017:5(5):1248-1255.

- Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.

Gülen T, Möller Westerberg C, Lyberg K, Ekoff M, Kolmert J, Bood J, Öhd J, James A, Dahlén SE, Nilsson G, Dahlén B.

Clin Exp Allergy 2017:47(7):909-917.

- Mastocytosis - the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease.

Gülen T, Hägglund H, Dahlén B, Nilsson G. Journal of Internal Medicine 2016:279(3):211-28.

- The presence of mast cell clonality in patients with unexplained anaphylaxis.

Gülen T, Hägglund H, Sander B, Dahlén B, Nilsson G. Clinical and Experimental Allergy 2014:44(9):1179-87.

- Flushing, fatigue, and recurrent anaphylaxis: a delayed diagnosis of mastocytosis.

Gülen T, Hägglund H, Dahlén SE, Sander B, Dahlén B, Nilsson G. Lancet 2014:383(9928):1608.

- High prevalence of anaphylaxis in patients with systemic mastocytosis - a single-centre experience.

Gülen T, Hägglund H, Dahlén B, Nilsson G. Clinical and Experimental Allergy 2014:44(1):121-9.