Hawley E Kunz1, George Makedonas2, Satish K Mehta3, Stephen K Tyring4, Ramya Vangipuram4, Heather Quiriarte5, Mayra Nelman-Gonzalez6, Duane L Pierson7, Brian E Crucian8. 1. Mayo Clinic, Rochester, MN, United States. 2. JES Tech, Houston, TX, United States. Electronic address: george.makedonas@nasa.gov. 3. JES Tech, Houston, TX, United States. 4. University of Texas Houston Health Sciences Center, Houston, TX, United States. 5. Louisiana State University, Baton Rouge, LA, United States. 6. KBR, Houston, Texas, United States. 7. NASA Johnson Space Center, 2101 E NASA Pkwy, Houston, TX 77058, United States. 8. NASA Johnson Space Center, 2101 E NASA Pkwy, Houston, TX 77058, United States. Electronic address: brian.crucian-1@nasa.gov.
Abstract
BACKGROUND: On long-duration spaceflight, most astronauts experience persistent immune dysregulation and the reactivation of latent herpesviruses, including varicella zoster virus (VZV). To understand the clinical risk of these perturbations to astronauts, we paralleled the immunology and virology work-up of astronauts to otherwise healthy terrestrial persons with acute herpes zoster. METHODS: Blood samples from 42 zoster patients - confirmed positive by PCR for VZV DNA in saliva (range from 100 to >285 million copies/mL) were analyzed for peripheral leukocyte distribution, T cell function, and plasma cytokine profiles via multi-parametric flow cytometry and multiplex bead-based immune-array assays. Patient findings were compared to normal value ranges specific for each assay that were defined in-house previously from healthy adult test subjects. RESULTS: Compared to the healthy adult ranges, the zoster patients possess (1) a higher proportion of constitutively activated T-cells, (2) a T-cell population skewed towards a more experienced maturation state, (3) depressed general T-cell function, and (4) a higher concentration of 20 of 22 measured plasma cytokines. DISCUSSION: The pattern of immune dysregulation in zoster patients is similar to that of astronauts during spaceflight who shed VZV DNA in their saliva. Because future deep space exploration missions will be of an unprecedented duration, prolonged immune depression and chronic viral reactivation threaten to manifest overt disease in exploration class astronauts.
BACKGROUND: On long-duration spaceflight, most astronauts experience persistent immune dysregulation and the reactivation of latent herpesviruses, including varicella zoster virus (VZV). To understand the clinical risk of these perturbations to astronauts, we paralleled the immunology and virology work-up of astronauts to otherwise healthy terrestrial persons with acute herpes zoster. METHODS: Blood samples from 42 zoster patients - confirmed positive by PCR for VZV DNA in saliva (range from 100 to >285 million copies/mL) were analyzed for peripheral leukocyte distribution, T cell function, and plasma cytokine profiles via multi-parametric flow cytometry and multiplex bead-based immune-array assays. Patient findings were compared to normal value ranges specific for each assay that were defined in-house previously from healthy adult test subjects. RESULTS: Compared to the healthy adult ranges, the zoster patients possess (1) a higher proportion of constitutively activated T-cells, (2) a T-cell population skewed towards a more experienced maturation state, (3) depressed general T-cell function, and (4) a higher concentration of 20 of 22 measured plasma cytokines. DISCUSSION: The pattern of immune dysregulation in zoster patients is similar to that of astronauts during spaceflight who shed VZV DNA in their saliva. Because future deep space exploration missions will be of an unprecedented duration, prolonged immune depression and chronic viral reactivation threaten to manifest overt disease in exploration class astronauts.
Authors: Stephanie S Krieger; Sara R Zwart; Satish Mehta; Honglu Wu; Richard J Simpson; Scott M Smith; Brian Crucian Journal: Front Immunol Date: 2021-08-24 Impact factor: 7.561