Cytomegalovirus infection is associated with thymic dysfunction and chronic graft-versus-host disease after pediatric hematopoietic stem cell transplantation

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-08, Vol.265, p.110302, Article 110302
• Main Authors: Kielsen, Katrine, Møller, Dina Leth, Pedersen, Anders Elm, Nielsen, Claus Henrik, Ifversen, Marianne, Ryder, Lars Peter, Müller, Klaus
• Format: Article
• Language: English
• Subjects: Adolescent; Bronchiolitis Obliterans Syndrome; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Child; Child, Preschool; Chronic Disease; Chronic graft-versus-host disease; CMV infection; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Female; Graft vs Host Disease - immunology; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Infant; Male; Regulatory T cells; Risk Factors; T-Lymphocytes, Regulatory - immunology; Thymic function; Thymus Gland - immunology
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110302

Pediatric hematopoietic stem cell transplantation (HSCT) is challenged by chronic graft-versus-host disease (cGvHD) significantly affecting survival and long-term morbidity, but underlying mechanisms including the impact of post-HSCT CMV infection are sparsely studied. We first investigated the impact of CMV infection for development of cGvHD in 322 children undergoing standard myeloablative HSCT between 2000 and 2018. Clinically significant CMV infection (n = 61) was an independent risk factor for chronic GvHD in a multivariable Cox regression analysis (HR = 2.17, 95% CI = 1.18–3.97, P = 0.013). We next explored the underlying mechanisms in a subcohort of 39 children. CMV infection was followed by reduced concentration of recent thymic emigrants (17.5 vs. 51.9 × 106/L, P = 0.048) and naïve CD4+ and CD8+ T cells at 6 months post-HSCT (all P