Frontiers in Immunology (Dec 2021)
Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity
- Ludmila Perelygina,
- Raeesa Faisthalab,
- Emily Abernathy,
- Min-hsin Chen,
- LiJuan Hao,
- Lionel Bercovitch,
- Diana K. Bayer,
- Lenora M. Noroski,
- Michael T. Lam,
- Maria Pia Cicalese,
- Waleed Al-Herz,
- Waleed Al-Herz,
- Arti Nanda,
- Joud Hajjar,
- Koen Vanden Driessche,
- Shari Schroven,
- Julie Leysen,
- Misha Rosenbach,
- Philipp Peters,
- Johannes Raedler,
- Michael H. Albert,
- Roshini S. Abraham,
- Hemalatha G. Rangarjan,
- David Buchbinder,
- David Buchbinder,
- Lisa Kobrynski,
- Anne Pham-Huy,
- Julie Dhossche,
- Charlotte Cunningham Rundles,
- Anna K. Meyer,
- Amy Theos,
- T. Prescott Atkinson,
- Amy Musiek,
- Mehdi Adeli,
- Ute Derichs,
- Christoph Walz,
- Renate Krüger,
- Horst von Bernuth,
- Horst von Bernuth,
- Horst von Bernuth,
- Horst von Bernuth,
- Christoph Klein,
- Joseph Icenogle,
- Fabian Hauck,
- Kathleen E. Sullivan
Affiliations
- Ludmila Perelygina
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- Raeesa Faisthalab
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- Emily Abernathy
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- Min-hsin Chen
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- LiJuan Hao
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- Lionel Bercovitch
- Department of Dermatology, Hasbro Children’s Hospital and Warren Alpert Medical School of Brown University, Providence, RI, United States
- Diana K. Bayer
- Department of Pediatrics, University of Iowa Stead Family Children’s Hospital, Iowa City, IA, United States
- Lenora M. Noroski
- Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
- Michael T. Lam
- Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
- Maria Pia Cicalese
- Pediatric Immunohematology and Bone Marrow Transplantation Unit and San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Istituto di Ricovero e Cura a Carattere Scientifico (National Institute for Research and Treatment) (IRCCS) San Raffaele Scientific Institute, Milan, Italy
- Waleed Al-Herz
- Department of Pediatrics, Kuwait University, Kuwait City, Kuwait
- Waleed Al-Herz
- Allergy and Clinical Immunology Unit, Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait
- Arti Nanda
- Pediatric Dermatology Unit, As’ad Al-Hamad Dermatology Center, Al-sabah Hospital, Kuwait City, Kuwait
- Joud Hajjar
- Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
- Koen Vanden Driessche
- Department of Pediatrics, Queen Mathilde Mother and Child Centre, Antwerp University Hospital, Antwerp, Belgium
- Shari Schroven
- Department of Pediatrics, Queen Mathilde Mother and Child Centre, Antwerp University Hospital, Antwerp, Belgium
- Julie Leysen
- 0Department of Dermatology, Queen Mathilde Mother and Child Centre, Antwerp University Hospital, Antwerp, Belgium
- Misha Rosenbach
- 1Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
- Philipp Peters
- 2Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- Johannes Raedler
- 2Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- Michael H. Albert
- 2Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- Roshini S. Abraham
- 3Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
- Hemalatha G. Rangarjan
- 4Department of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH, United States
- David Buchbinder
- 5Department of Hematology, Children’s Hospital of Orange County, Orange, CA, United States
- David Buchbinder
- 6Department of Pediatrics, University of California at Irvine, Orange, CA, United States
- Lisa Kobrynski
- 7Allergy/Immunology Section, Emory University, Atlanta, GA, United States
- Anne Pham-Huy
- 8Department of Pediatrics, University of Ottawa and Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada
- Julie Dhossche
- 9Department of Dermatology, Oregon Health and Science University, Portland, OR, United States
- Charlotte Cunningham Rundles
- 0Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Anna K. Meyer
- 1Department of Pediatrics, National Jewish Health, Denver, CO, United States
- Amy Theos
- 2Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, United States
- T. Prescott Atkinson
- 3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
- Amy Musiek
- 4Division of Dermatology, Washington University School of Medicine, St. Louis, MO, United States
- Mehdi Adeli
- 5Division of Immunology and Allergy, Sidra Medicine and Hamad Medical Corporation, Doha, Qatar
- Ute Derichs
- 6Center for Pediatric and Adolescent Medicine, University Medical Hospital Mainz, Mainz, Germany
- Christoph Walz
- 7Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
- Renate Krüger
- 8Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Horst von Bernuth
- 8Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Horst von Bernuth
- 9Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany
- Horst von Bernuth
- 0Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Horst von Bernuth
- 1Labor Berlin GmbH, Department of Immunology, Berlin, Germany
- Christoph Klein
- 2Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- Joseph Icenogle
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, United States
- Fabian Hauck
- 2Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- Kathleen E. Sullivan
- 2Division of Allergy Immunology, Department of Pediatrics, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.796065
- Journal volume & issue
-
Vol. 12
Abstract
Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.
Keywords
- inborn errors of immunity
- primary immunodeficiency
- vaccine-derived rubella viruses
- granulomatous inflammation
- skin lesion
- neutrophils
