1. Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity
- Author
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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, 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, 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, Christoph Klein, Joseph Icenogle, Fabian Hauck, Kathleen E. Sullivan, Perelygina, L., Faisthalab, R., Abernathy, E., Chen, M. -H., Hao, L., Bercovitch, L., Bayer, D. K., Noroski, L. M., Lam, M. T., Cicalese, M. P., Al-Herz, W., Nanda, A., Hajjar, J., Vanden Driessche, K., Schroven, S., Leysen, J., Rosenbach, M., Peters, P., Raedler, J., Albert, M. H., Abraham, R. S., Rangarjan, H. G., Buchbinder, D., Kobrynski, L., Pham-Huy, A., Dhossche, J., Cunningham Rundles, C., Meyer, A. K., Theos, A., Atkinson, T. P., Musiek, A., Adeli, M., Derichs, U., Walz, C., Kruger, R., von Bernuth, H., Klein, C., Icenogle, J., Hauck, F., and Sullivan, K. E.
- Subjects
Male ,inborn errors of immunity ,Neutrophils ,Immunology ,skin lesion ,primary immunodeficiency ,Cohort Studies ,Th2 Cells ,neutrophils ,granulomatous inflammation ,granuloma treatments ,Humans ,Immunology and Allergy ,Antigens, Viral ,Rubella ,Aged ,Original Research ,Inflammation ,Granuloma ,Tumor Necrosis Factor-alpha ,Macrophages ,Genetic Diseases, Inborn ,Hematopoietic Stem Cell Transplantation ,Immunologic Deficiency Syndromes ,Receptors, Interleukin-1 ,RC581-607 ,Middle Aged ,Immunohistochemistry ,macrophages ,vaccine-derived rubella viruses ,Cytokines ,Female ,Human medicine ,Disease Susceptibility ,Immunologic diseases. Allergy ,Rubella virus - 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.
- Published
- 2021