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Article ; Online: Are blood cytokines reliable biomarkers of allergic disease diagnosis and treatment responses?

Radonjic-Hoesli, Susanne / Pavlov, Nikolay / Simon, Hans-Uwe / Simon, Dagmar

The Journal of allergy and clinical immunology

2022 Volume 150, Issue 2, Page(s) 251–258

Abstract: With the development of targeted therapies for allergic diseases, the need for biomarkers supporting disease diagnosis and management has increased. Recent research has elucidated the pattern of cytokines and their distinct roles in the pathogenesis of ... ...

Abstract	With the development of targeted therapies for allergic diseases, the need for biomarkers supporting disease diagnosis and management has increased. Recent research has elucidated the pattern of cytokines and their distinct roles in the pathogenesis of allergic diseases. This means that cytokines should be considered as biomarkers. In this review article, we summarize published findings and critically discuss the use of cytokine measurements in association with disease diagnosis and management. Among the variety of suggested cytokines, thymus and activation-regulated chemokine (TARC) stands out and can indeed serve as a biomarker of atopic dermatitis. Both biologic characteristics and technical issues determine the reliability and limit the use of blood cytokines as biomarkers.
MeSH term(s)	Biomarkers ; Chemokine CCL17 ; Cytokines ; Humans ; Reproducibility of Results ; Severity of Illness Index
Chemical Substances	Biomarkers ; Chemokine CCL17 ; Cytokines
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2022.06.008
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Article ; Online: Eosinophils in skin diseases.

Radonjic-Hoesli, Susanne / Brüggen, Marie-Charlotte / Feldmeyer, Laurence / Simon, Hans-Uwe / Simon, Dagmar

Seminars in immunopathology

2021 Volume 43, Issue 3, Page(s) 393–409

Abstract: Eosinophil infiltration is a common finding in a broad spectrum of skin diseases, despite the fact that the skin is devoid of eosinophils under physiologic conditions. Although cutaneous eosinophilia is reactive, cytokine-mediated in most cases, diseases ...

Abstract	Eosinophil infiltration is a common finding in a broad spectrum of skin diseases, despite the fact that the skin is devoid of eosinophils under physiologic conditions. Although cutaneous eosinophilia is reactive, cytokine-mediated in most cases, diseases with an intrinsic mutation-mediated clonal expansion of eosinophils can also manifest on the skin. As eosinophils are involved in host defense, regulate immune responses, generate pruritus, induce remodeling and fibrosis, and can cause tissue damage, they have the capacity to actively contribute to the pathogenesis of diseases. Recent research provided deeper insights in the mechanisms, e.g., bacterial and viral clearance, blister formation, recruitment of cytotoxic T cells, and generation of pruritus, by which eosinophils might come into action. This review aims at providing an overview on the clinical presentations of eosinophil-associated dermatoses and the current understanding of their pathogenic role in these diseases. Further, we discuss the effects of therapies targeting eosinophils.
MeSH term(s)	Cytokines ; Eosinophilia/etiology ; Eosinophils ; Humans ; Skin ; Skin Diseases/etiology
Chemical Substances	Cytokines
Language	English
Publishing date	2021-06-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-021-00868-7
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Article ; Online: Characteristics of Dermatological Patients With Blood Eosinophilia: A Retrospective Analysis of 453 Patients.

Radonjic-Hoesli, Susanne / Martignoni, Zora / Cazzaniga, Simone / Furrer, Dominique Isabel / Simon, Hans-Uwe / Bürgler, Christina / Simon, Dagmar

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 5, Page(s) 1229–1237.e8

Abstract: Background: Skin diseases associated with blood or tissue eosinophilia are common. Because these have various clinical manifestations, making the correct diagnosis can be challenging. So far, dermatological patients with concomitant blood eosinophilia ... ...

Abstract	Background: Skin diseases associated with blood or tissue eosinophilia are common. Because these have various clinical manifestations, making the correct diagnosis can be challenging. So far, dermatological patients with concomitant blood eosinophilia have not been characterized. Objective: To investigate patterns of dermatological patients with concomitant blood eosinophilia to obtain information helpful for optimizing disease management. Methods: In this retrospective study, demographic and clinical data and diagnostic test results of all patients presenting with dermatoses associated with blood eosinophilia referred to a university center from 2014 to 2018 were extracted from the electronic patient charts and evaluated using descriptive and semantic map analyses. Results: A total of 453 patients (51.4% females; mean age, 58.4 ± 21.7 years) were included and grouped according to blood absolute eosinophil counts: severe, greater than or equal to 1.5 G/L (n = 87; 19.2%); moderate, 1.0 to 1.49 G/L (n = 73; 16.1%); and mild eosinophilia, 0.5 to 0.99 G/L (n = 293; 64.7%). Most patients presented with chronic (64.6%), generalized skin lesions (75.9%), and pruritus (88.1%). Statistical analyses revealed 3 distinct patterns: (1) mild eosinophilia associated with localized skin disease, age less than 50 years, history of atopy, and diagnosis of eczema or infectious disease; (2) moderate eosinophilia linked to generalized skin lesions, pruritus, age more than 70 years, and autoimmune bullous disease; and (3) severe eosinophilia associated with diagnosis of hypereosinophilic syndromes, drug hypersensitivity, or malignant disease. Conclusions: Based on the pattern analysis of patients with dermatoses associated with blood eosinophilia, a diagnostic workup has been developed aiming at setting the correct differential diagnosis in a feasible and effective manner.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Eosinophils/pathology ; Female ; Humans ; Hypereosinophilic Syndrome ; Male ; Middle Aged ; Pruritus/etiology ; Retrospective Studies ; Skin Diseases
Language	English
Publishing date	2022-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2022.02.018
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Article ; Online: Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation.

Thormann, Kathrin / Lüthi, Anne-Sophie / Deniau, Felix / Heider, Anja / Cazzaniga, Simone / Radonjic-Hoesli, Susanne / Lehmann, Mathias / Schlapbach, Christoph / Herzog, Elio L / Kreuzer, Marco / Zinkernagel, Martin S / Akdis, Cezmi A / Zysset-Burri, Denise C / Simon, Hans-Uwe / Simon, Dagmar

Allergy

2024 Volume 79, Issue 4, Page(s) 937–948

Abstract: Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at ... ...

Abstract	Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD.
MeSH term(s)	Humans ; Pilot Projects ; Proteomics ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/metabolism ; Inflammation ; Eye Diseases ; Fibrosis ; Severity of Illness Index ; Treatment Outcome ; Antibodies, Monoclonal, Humanized
Chemical Substances	dupilumab (420K487FSG) ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2024-02-05
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.16045
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Article: Successful treatment of refractory folliculitis decalvans with apremilast.

Fässler, Mirjam / Radonjic-Hoesli, Susanne / Feldmeyer, Laurence / Imstepf, Valentina / Pelloni, Lorenzo / Yawalkar, Nikhil / de Viragh, Pierre A

JAAD case reports

2020 Volume 6, Issue 10, Page(s) 1079–1081

Language	English
Publishing date	2020-08-20
Publishing country	United States
Document type	Case Reports
ZDB-ID	2834220-3
ISSN	2352-5126
ISSN	2352-5126
DOI	10.1016/j.jdcr.2020.08.019
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Article ; Online: PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis.

Nature communications

2023 Volume 14, Issue 1, Page(s) 2471

Abstract: T helper 9 ( ... ...

Abstract	T helper 9 (T
MeSH term(s)	Humans ; Glucose/metabolism ; Glycolysis ; Inflammation/pathology ; Interleukin-13/metabolism ; Interleukin-9 ; PPAR gamma/genetics ; PPAR gamma/metabolism ; T-Lymphocytes, Helper-Inducer
Chemical Substances	Glucose (IY9XDZ35W2) ; Interleukin-13 ; Interleukin-9 ; PPAR gamma ; PPARG protein, human
Language	English
Publishing date	2023-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38233-x
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Article ; Online: Eosinophils.

Radonjic-Hösli, Susanne / Simon, Hans-Uwe

Chemical immunology and allergy

2014 Volume 100, Page(s) 193–204

Abstract: In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather ...

Abstract	In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation.
MeSH term(s)	Animals ; Cytokines/metabolism ; Eosinophil Granule Proteins/metabolism ; Eosinophilia/metabolism ; Eosinophilia/pathology ; Eosinophilia/therapy ; Eosinophils/immunology ; Eosinophils/metabolism ; Eosinophils/pathology ; Glucocorticoids/therapeutic use ; Humans ; Mice ; Receptors, Cytokine/metabolism ; Transcription Factors/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	Cytokines ; Eosinophil Granule Proteins ; Glucocorticoids ; Receptors, Cytokine ; Transcription Factors ; Transforming Growth Factor beta
Language	English
Publishing date	2014
Publishing country	Switzerland
Document type	Journal Article
ISSN	1662-2898 ; 1660-2242
ISSN (online)	1662-2898
ISSN	1660-2242
DOI	10.1159/000358735
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Article ; Online: Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

Sidler, Daniel / Born, Alexander / Schietzel, Simeon / Horn, Michael P / Aeberli, Daniel / Amsler, Jennifer / Möller, Burkhard / Njue, Linet M / Medri, Cesare / Angelillo-Scherrer, Anne / Borradori, Luca / Seyed Jafari, S Morteza / Radonjic-Hoesli, Susanne / Chan, Andrew / Hoepner, Robert / Bacher, Ulrike / Mani, Laila-Yasmin / Iype, Joseena Mariam / Suter-Riniker, Franziska /

Staehelin, Cornelia / Nagler, Michael / Hirzel, Cedric / Maurer, Britta / Moor, Matthias B

RMD open

2022 Volume 8, Issue 1

Abstract: Background: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with ... ...

Abstract	Background: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. Methods: We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. Results: 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. Conclusion: This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunity, Cellular ; SARS-CoV-2 ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Language	English
Publishing date	2022-03-31
Publishing country	England
Document type	Clinical Study ; Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2021-002166
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Article ; Online: PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract T helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we ... ...

Abstract	Abstract T helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in TH9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in TH cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human TH9 cells.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Urticaria and Angioedema: an Update on Classification and Pathogenesis.

Radonjic-Hoesli, Susanne / Hofmeier, Kathrin Scherer / Micaletto, Sara / Schmid-Grendelmeier, Peter / Bircher, Andreas / Simon, Dagmar

Clinical reviews in allergy & immunology

2017 Volume 54, Issue 1, Page(s) 88–101

Abstract: Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. In the last years, urticaria has increasingly attracted notice to clinicians and researchers, last but not least inspired by the approval of omalizumab, an anti- ...

Abstract	Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. In the last years, urticaria has increasingly attracted notice to clinicians and researchers, last but not least inspired by the approval of omalizumab, an anti-IgE antibody, for urticaria treatment. There is wide consensus on the clinical classification based on duration and elicitation. However, the pathogenesis is incompletely understood. This review summarizes current guidelines for the management and novel insights in the pathogenesis of urticaria with special focus on their impact on clinical praxis. The classification of urticaria subgroups is mainly based on clinical criteria: acute and chronic urticaria (CU). Chronic urticaria comprises both chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) that includes physical and non-physical urticarias. Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activation, and investigating underlying autoimmune processes in chronic spontaneous urticarial. Currently, non-sedating antihistamines and omalizumab, an antiimmunoglobulin E antibody, are recommended for the therapy of chronic urticaria, as both exhibit a favorable efficacy and safety profile. Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria.
MeSH term(s)	Angioedema/immunology ; Angioedema/therapy ; Anti-Allergic Agents/therapeutic use ; Antibodies, Anti-Idiotypic/therapeutic use ; Chronic Disease ; Humans ; Mast Cells/immunology ; Omalizumab/therapeutic use ; Urticaria/immunology ; Urticaria/therapy
Chemical Substances	Anti-Allergic Agents ; Antibodies, Anti-Idiotypic ; anti-IgE antibodies ; Omalizumab (2P471X1Z11)
Language	English
Publishing date	2017-07-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1239045-8
ISSN	1559-0267 ; 1080-0549
ISSN (online)	1559-0267
ISSN	1080-0549
DOI	10.1007/s12016-017-8628-1
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