Frontiers in Immunology (Jul 2022)
The Number of MRGPRX2-Expressing Cells Is Increased in Skin Lesions of Patients With Indolent Systemic Mastocytosis, But Is Not Linked to Symptom Severity
- Polina Pyatilova,
- Polina Pyatilova,
- Tameem Ashry,
- Tameem Ashry,
- Tameem Ashry,
- Yanyan Luo,
- Yanyan Luo,
- Jiajun He,
- Jiajun He,
- Jiajun He,
- Hanna Bonnekoh,
- Hanna Bonnekoh,
- Qingqing Jiao,
- Qingqing Jiao,
- Qingqing Jiao,
- Sherezade Moñino-Romero,
- Sherezade Moñino-Romero,
- Man Hu,
- Man Hu,
- Jörg Scheffel,
- Jörg Scheffel,
- Stefan Frischbutter,
- Stefan Frischbutter,
- Maud A. W. Hermans,
- Bradford A. Youngblood,
- Marcus Maurer,
- Marcus Maurer,
- Frank Siebenhaar,
- Frank Siebenhaar,
- Pavel Kolkhir,
- Pavel Kolkhir
Affiliations
- Polina Pyatilova
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Polina Pyatilova
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Tameem Ashry
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Tameem Ashry
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Tameem Ashry
- Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Yanyan Luo
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Yanyan Luo
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Jiajun He
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Jiajun He
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Jiajun He
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Hanna Bonnekoh
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Hanna Bonnekoh
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Qingqing Jiao
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Qingqing Jiao
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Qingqing Jiao
- Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Sherezade Moñino-Romero
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Sherezade Moñino-Romero
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Man Hu
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Man Hu
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Jörg Scheffel
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Jörg Scheffel
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Stefan Frischbutter
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Stefan Frischbutter
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Maud A. W. Hermans
- Department of Internal Medicine, Section Allergy and Clinical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands
- Bradford A. Youngblood
- Allakos Inc., San Carlos, CA, United States
- Marcus Maurer
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Marcus Maurer
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Frank Siebenhaar
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Frank Siebenhaar
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- Pavel Kolkhir
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Pavel Kolkhir
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.930945
- Journal volume & issue
-
Vol. 13
Abstract
BackgroundRecently, the expression of the mast cell (MC) receptor Mas-related G protein–coupled receptor X2 (MRGPRX2) has been detected in lesional skin of adult patients with cutaneous mastocytosis. As of yet, little is known about the clinical relevance of MRGPRX2 and its agonists in patients with mastocytosis, including indolent systemic mastocytosis (ISM).MethodsMRGPRX2 and MRGPRX2 agonists, cortistatin (CST), and major basic protein (MBP) were analyzed in lesional and non-lesional skin of patients with ISM and skin of healthy controls by immunohistochemistry. Co-localization of MRGPRX2 and MRGPRX2-mRNA with the MC marker tryptase was assessed by immunofluorescence microscopy and in situ hybridization, respectively. We assessed clinical, demographic, and laboratory data, including mastocytosis activity score (MAS), serum tryptase, and KIT D816V allele burden.ResultsThe number of MRGPRX2-expressing (MRGPRX2+) cells, MRGPRX2-mRNA+ MCs, and CST-expressing (CST+) and MBP-expressing (MBP+) cells was significantly higher in lesional skin as compared to non-lesional skin and/or skin of healthy controls (all p < 0.05). Increased numbers of MRGPRX2+ cells, MRGPRX2-mRNA+ MCs, and CST+ and MBP+ cells were not associated with clinical and laboratory features of ISM, including disease burden, symptom severity, evidence of anaphylaxis, and tryptase levels.ConclusionsSkin lesions of patients with ISM showed high numbers of MRGPRX2+ cells, although they were not linked to symptom severity. Clinical relevance of the MRGPRX2-mediated pathway of MC activation in ISM remains unclear and should be investigated in further studies.
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