Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping
Abstract Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-81060-3 |
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| author | Hannah L. Cornman Martin P. Alphonse Arbor Dykema Alexander L. Kollhoff Kevin K. Lee Jaya Manjunath Emily Z Ma Varsha Parthasarathy Junwen Deng Thomas Pritchard Anusha Kambala Melika Marani Kayla A. Parr Javid P. Mohammed Madan M. Kwatra Jay H. Bream Won Jin Ho Shawn G. Kwatra |
| author_facet | Hannah L. Cornman Martin P. Alphonse Arbor Dykema Alexander L. Kollhoff Kevin K. Lee Jaya Manjunath Emily Z Ma Varsha Parthasarathy Junwen Deng Thomas Pritchard Anusha Kambala Melika Marani Kayla A. Parr Javid P. Mohammed Madan M. Kwatra Jay H. Bream Won Jin Ho Shawn G. Kwatra |
| author_sort | Hannah L. Cornman |
| collection | DOAJ |
| description | Abstract Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls. We found that the index patient had a novel form of erythroderma characterized by increased interleukin (IL)-13- and IL-17-producing γVδ2 T cells, basophils, and activated platelets. Whole-genome sequencing of PBMCs and immunofluorescence staining of skin biopsies revealed increased expression of Th2- (IL-13, IL-4Rα) and Th17-associated markers (IL-17, IL-17Rα) and non-functional mutations associated with Th2 and Th17 signaling, demonstrating that PBMCs can reflect cutaneous disease pathology. Targeted intervention via dual dupilumab and secukinumab therapy resulted in complete disease control and reduction of immunopathogenic cell populations and cytokines. This study highlights a novel form of erythroderma with concomitant Th2 and Th17 dysregulation and introduces a minimally invasive peripheral blood-based immunophenotyping platform that offers a personalized medicine approach to the management of systemic inflammatory diseases. |
| format | Article |
| id | doaj-art-7ff065e980d441fb9f153e827441f010 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7ff065e980d441fb9f153e827441f0102025-01-19T12:19:14ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-81060-3Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotypingHannah L. Cornman0Martin P. Alphonse1Arbor Dykema2Alexander L. Kollhoff3Kevin K. Lee4Jaya Manjunath5Emily Z Ma6Varsha Parthasarathy7Junwen Deng8Thomas Pritchard9Anusha Kambala10Melika Marani11Kayla A. Parr12Javid P. Mohammed13Madan M. Kwatra14Jay H. Bream15Won Jin Ho16Shawn G. Kwatra17Department of Dermatology, University of Maryland School of MedicineDepartment of Dermatology, Johns Hopkins University School of MedicineDepartment of Dermatology, Johns Hopkins University School of MedicineDepartment of Dermatology, University of Maryland School of MedicineDepartment of Dermatology, Johns Hopkins University School of MedicineDepartment of Dermatology, George Washington University School of Medicine and Health SciencesDepartment of Dermatology, University of Maryland School of MedicineDepartment of Dermatology, George Washington University School of Medicine and Health SciencesDepartment of Dermatology, University of Maryland School of MedicineDepartment of Dermatology, University of Maryland School of MedicineDepartment of Dermatology, George Washington University School of Medicine and Health SciencesDepartment of Dermatology, Johns Hopkins University School of MedicineDuke Cancer Institute Flow Cytometry Core, Department of Immunology, Duke University School of MedicineDuke Cancer Institute Flow Cytometry Core, Department of Immunology, Duke University School of MedicineDepartment of Anesthesiology, Duke University School of MedicineDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public HealthDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineDepartment of Dermatology, University of Maryland School of MedicineAbstract Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls. We found that the index patient had a novel form of erythroderma characterized by increased interleukin (IL)-13- and IL-17-producing γVδ2 T cells, basophils, and activated platelets. Whole-genome sequencing of PBMCs and immunofluorescence staining of skin biopsies revealed increased expression of Th2- (IL-13, IL-4Rα) and Th17-associated markers (IL-17, IL-17Rα) and non-functional mutations associated with Th2 and Th17 signaling, demonstrating that PBMCs can reflect cutaneous disease pathology. Targeted intervention via dual dupilumab and secukinumab therapy resulted in complete disease control and reduction of immunopathogenic cell populations and cytokines. This study highlights a novel form of erythroderma with concomitant Th2 and Th17 dysregulation and introduces a minimally invasive peripheral blood-based immunophenotyping platform that offers a personalized medicine approach to the management of systemic inflammatory diseases.https://doi.org/10.1038/s41598-024-81060-3 |
| spellingShingle | Hannah L. Cornman Martin P. Alphonse Arbor Dykema Alexander L. Kollhoff Kevin K. Lee Jaya Manjunath Emily Z Ma Varsha Parthasarathy Junwen Deng Thomas Pritchard Anusha Kambala Melika Marani Kayla A. Parr Javid P. Mohammed Madan M. Kwatra Jay H. Bream Won Jin Ho Shawn G. Kwatra Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping Scientific Reports |
| title | Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping |
| title_full | Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping |
| title_fullStr | Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping |
| title_full_unstemmed | Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping |
| title_short | Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping |
| title_sort | targeted dual biologic therapy for erythroderma of unknown etiology guided by high parameter peripheral blood immunophenotyping |
| url | https://doi.org/10.1038/s41598-024-81060-3 |
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