Inflammatory Cytokine Profile in Individuals with Inherited Chromosomally Integrated Human Herpesvirus 6

• Published in: Biology of blood and marrow transplantation Vol. 26; no. 2; pp. 254 - 261
• Main Authors: Weschke, Daniel P., Leisenring, Wendy M., Lawler, Richard L., Stevens-Ayers, Terry, Huang, Meei-Li, Jerome, Keith R., Zerr, Danielle M., Hansen, John A., Boeckh, Michael, Hill, Joshua A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Cytokines; GVHD; iciHHV-6; Transplant; iciHHV-6; GVHD; Cytokines; Transplant
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2019.10.023

•Hematopoietic cell transplantation (HCT) recipients in whom the donor or recipient had inherited chromosomally integrated human herpesvirus 6 (iciHHV-6pos) have higher plasma C-reactive protein and TNFRp55 cytokine concentrations.•IciHHV-6pos HCT recipients had earlier-onset graft-versus-host disease by a median of 7 days.•There were no differences in cytokine levels among healthy donors with or without iciHHV-6. Acute graft-versus-host-disease (aGVHD) is a major complication following hematopoietic cell transplantations (HCTs). We have shown that HCT recipients in whom either the donor or patient had inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) have a higher incidence of developing more severe aGVHD. Previous studies established that increased proinflammatory cytokines are associated with increased risk for aGVHD and nonrelapse mortality post-HCT. We hypothesized that HCT recipients with donor or recipient iciHHV-6 (iciHHV-6pos HCT cases) will have higher cytokine levels compared with HCT recipients without iciHHV-6 (iciHHV-6neg HCT controls). We identified 64 iciHHV-6pos HCT cases with plasma from days 7, 14, and/or 21 post-HCT and before aGVHD onset in patients who developed aGVHD. We identified 64 iciHHV-6neg HCT controls matched for aGVHD risk factors. We also identified 28 donors with iciHHV-6 and 56 matched donors without iciHHV-6. We measured plasma cytokine concentrations for IL-6, suppression of tumorigenicity 2, T cell immunoglobulin and mucin-domain containing 3, TNFα, soluble TNF receptor 1 (TNFRp55), and C-reactive protein (CRP). We used Mann-Whitney tests and repeated-measures models to compare cytokine levels. iciHHV-6pos HCT cases had higher CRP levels on day 7 and day 21 and higher TNFRp55 levels on day 14 and day 21 compared with iciHHV-6neg HCT controls. These findings were recapitulated in a repeated-measures model. The differences were most evident among patients who subsequently developed aGVHD grades 2 to 4. Additionally, iciHHV-6pos HCT cases had earlier-onset aGVHD (median, 20 versus 27 days post-HCT; P = .02). There were no differences in cytokine levels among healthy donors with or without iciHHV-6. This study demonstrates that HCT recipients with iciHHV-6 have higher proinflammatory cytokines that may be associated with increased risk for aGVHD.