Gap IM7: It is necessary to correlate the observed effects of spaceflight-associated immune system dysregulation with known terrestrial clinical conditions.
Last Published:  07/30/21 01:05:31 PM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Closed
Closure Rationale
The studies that were funded under this gap have been successfully completed. In these studies, the unique panel of immune assays used to characterize immune function in astronauts (assays which are not routinely used in the terrestrial clinical realm) were applied to two terrestrial patient population: one group of otherwise healthy patients who presented with acute herpes zoster (Shingles) and the other population comprised of patients hospitalized with sepsis. The intent was to use this ground clinical information to aid in interpreting the in-flight data, and help to derive specific clinical risks for long term deep space missions. The studies showed that both the sepsis and the Zoster patients exhibited immune dysregulation which was similar to but of much greater magnitude to the dysregulation observed in astronauts during spaceflight. These data indicate that the immunological observations in astronauts may indeed reflect legitimate clinical risks, particularly for upcoming deep space missions, and that their immune dysfunction places astronauts at the subclinical level of a continuum of immune dysfunction that is short of the threshold that would lead to overt clinical presentation. Given that the target milestones for this gap have been achieved and no further work is planned under this gap, this gap is being closed. Work on other areas of the immune risk continue under other gaps.

Publications:

Kunz HE, Makedonas G, Mehta SK, Tyring SK, Vangipuram R, Quiriarte H, Nelman-Gonzalez M, Pierson DL, Crucian BE. Zoster Patients on Earth and Astronauts in Space Share Similar Immunologic Profiles, Life Sciences in Space Research (2019), doi: https://doi.org/10.1016/j.lssr.2019.10.001

Mehta SK, Nelman-Gonzalez M, Tyring SK, Tong Y, Beitman A, Crucian BE, Renner AN, Pierson DL. Localization of VZV in saliva of zoster patients. J Med Virol. 2017 Sep;89(9):1686-1689. doi: 10.1002/jmv.24807. Epub 2017 May 2.

Feuerecker M, Sudhoff L, Crucian B, Pagel JI, Sams C, Strewe C, Guo A, Schelling G, Briegel J, Kaufmann I, Choukèr A. Early immune anergy towards recall antigens and mitogens in patients at onset of septic shock. Nature Scientific Reports; 2018; 8:1754

Guo A, Srinath J, Feuerecker M, Crucian B, Briegel J, Boulesteix AL, Kaufmann I, Choukèr A. Immune function testing in sepsis patients receiving sodium selenite. J Crit Care. 2019 Aug;52:208-212. doi: 10.1016/j.jcrc.2019.05.001. Epub 2019 May 4.

Closure Documentation:
No Closure Documentation Available
Description

Initial  State:   The field of clinical immunology, defined as assays with demonstrated clinical utility for physicians, is actually a fairly small field.  Commonly used immunology assays are a CBC, CD4 counts, antibody titers.   There are other more specific assays that are also used, such as PCR for DNA detection and various protein ELISAs.   These assays are largely not relevant for spaceflight investigations (Astronauts are not HIV patients…).  Most of the assays that define the unique immune alterations associated with spaceflight fall under the ‘research’ category.   For this reason, the clinical-descriptive in-flight studies are basically defining a novel immune dysregulation by assessing a variety of leukocyte distribution and immune cell functional characteristics, parameters that are not routinely used (yet) in clinical medicine.   Therefore, the clinical correlations of the immune alterations observed during spaceflight are unknown. 

 

It is relatively simple to determine such clinical correlations by applying the assays that define spaceflight-associated immune dysregulation to terrestrial patient populations.  In particular, target populations should contain the adverse clinical events thought to be in-flight risks for exploration class missions.  For example, persistent reactivation of latent VZV is a clinical risk for exploration, as ISS studies have demonstrated the phenomenon does not resolve during 6 months orbital flight.   However the immune decrements that precede VZV reactivation have not been investigated.   This is because healthy individuals to not present to their physician until symptoms and infection are well established (chicken pox or shingles).   Therefore, the immune alterations that lead to susceptibility to reactivation have never been established.   Performing terrestrial clinical immune studies that parallel in-flight investigations has been a SRP directive, and will greatly assist our interpretation of in-flight data, and our determination of crew clinical risks from specific immune alterations.

 

 


Intermediate Steps/Metrics:
  This Gap will incrementally close as studies to assess various target patient populations are completed.  

 

  1. Execute ESA Clinical Study.  This study will provide clinical immune data for ICU stress/sepsis patients.  This study is currently underway in Munich, Germany.   This study assesses cytokine profiles and herpesvirus reaction using Intensive Care Unit stay as a stress model.   Upon completion, Gap closure will be ~15%. 
  2. Execute Tyring Clinical Study.  This study will provide clinical immune data for Shingles patients.  Upon completion, Gap closure will be ~35%.
  3. Execute JSC Clinical Correlations study.  This study will provide clinical immune data for infectious disease, allergy, hypersensitivity, etc..  This study will be operated out of NASA-JSC, to allow live-cell assays to be performed.   Overseas studies require a frozen sample, which precludes live-cell analysis for NASA assays.  Upon completion, Gap closure will be ~85%.
  4. Re-interpret in-flight immune data in the context of terrestrial clinical data.  This activity will derive crew clinical risk related to immune dysregulation during exploration class deep-space missions.

 

Approach:  Engage physician researchers as collaborators to initiate terrestrial clinical studies.   Apply assays that define in-flight immune dysregulation.

Target for Closure
Complete appropriate terrestrial clinical evaluations using flight-validated immune monitoring panels.  Appropriate clinical populations display adverse medical conditions similar to those anticipated to be a health risk during exploration class spaceflight:  infectious disease, hypersensitivities, autoimmunity, malignancies, etc.  Re-interpret in-flight data in the context of terrestrial clinical data.
Mappings
Risk Risk of Adverse Health Event Due to Altered Immune Response
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Multi-Disciplinary Research Plans

Documentation:
No Documentation Available