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Project Title:  The Impact of Long Duration Spaceflight on the Function of B-cells and Biomarkers of Inflammation Reduce
Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 11/01/2016  
End Date: 10/31/2018  
Task Last Updated: 08/31/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Spielmann, Guillaume  Ph.D. / Louisiana State University 
Address:  112 Long Fieldhouse 
School of Kinesiology 
Baton Rouge , LA 70803-0001 
Email: Gspielmann@lsu.edu 
Phone: 225-578-2926  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Louisiana State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Campbell, John  Ph.D. Louisiana State University and A&M College 
Crucian, Brian  Ph.D. NASA Johnson Space Center 
Laughlin, Mitzi  Ph.D. University of Houston 
Simpson, Richard  Ph.D. University of Houston 
Project Information: Grant/Contract No. NNX17AB16G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-Crew Health (FLAGSHIP, NSBRI, OMNIBUS). Appendix A-Crew Health, Appendix B-NSBRI, Appendix C-Omnibus 
Grant/Contract No.: NNX17AB16G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM07:It is necessary to correlate the observed effects of spaceflight-associated immune system dysregulation with known terrestrial clinical conditions (IRP Rev E)
Flight Assignment/Project Notes: Postflight sample analysis

NOTE: Extended to 10/31/2018 per NSSC information (Ed., 9/12/18)

Task Description: Long duration spaceflights reportedly induce dysregulation of the immune system, which is considered a risk to astronaut safety and mission success. Recent studies have examined the impact of long-duration spaceflight on specific markers of adaptive and innate immunity, but no study to date has comprehensively evaluated humoral immunity and serological markers of B-cell function. The aim of this study was to characterize changes in B-cell numbers and phenotypes, along with plasma immunoglobulins and polyclonal free light chains (FLC) – near ‘real-time’ biomarkers of immunoglobulin synthesis – in response to a ~6-month mission to the International Space Station (ISS).

Methods: Whole blood and plasma samples were collected before flight, during ("Early flight", "Mid-flight" and "Late flight"), immediately upon return, and during a recovery period (R+18, R+30/R+33 and R+60/R+66) from 23 ISS crewmembers and 6 healthy ground-based controls. Total plasma immunoglobulin (Ig) and FLC levelss were measured throughout the duration of the mission

Results: There was no effect of spaceflight on kappa FLC concentrations (p>0.05), and only a marginal reduction was observed in lambda FLC levels upon return to Earth (p<0.05). Furthermore, IgG and IgM remained unchanged during and after spaceflight, when compared to pre-flight values (p>0.05). Of note, plasma IgA concentrations were elevated in-flight when compared to baseline and recovery values (p<0.05).

Conclusion: These results indicate that B-cell homeostasis is maintained during long duration spaceflight in astronauts, advocating for potential in-flight vaccination as viable countermeasures against viral reactivation during exploration-class missions.

Research Impact/Earth Benefits: This project bolstered our understanding of how physical and psychological stressors impact our immune system. We found that spaceflight-induced physical and psychological stressors led to an increase in serum IgA concentration, and that B-cell and plasma cell homeostasis were not affected by long duration spaceflight. Furthermore, this project highlighted the use of novel biomarkers of immune activation, plasma Free Light Chains, to monitor immune function in special populations (children, first responders, soldiers, elderly, etc.).

Task Progress & Bibliography Information FY2019 
Task Progress: The task is completed.

This study investigated the impact of long duration spaceflight on plasma immunoglobulin Free Light Chains (FLC), IgA, IgG, and IgM. Additionally, we correlated changes in plasma FLC with salivary FLC, to identify non-invasive methods aimed at assessing changes in immune function during spaceflight.

There was no change in plasma IgG and IgM concentrations in astronauts and ground-based controls throughout the mission (p>0.05). Astronauts exhibited an increase in plasma IgA during flight, when compared to baseline values (L-60/45). Upon return on Earth, plasma IgA concentrations decreased from in-flight levels, and were back to pre-flight values (L-60/L-45) during recovery (R+30) (p=0.047). All changes withstood adjustment for latent viral reactivation status and DNA load, along with estimated Glomerular Filtration Rate, an estimated measure of kidney function.

There was no effect of spaceflight on plasma Kappa FLC (p>0.05), and only a minor decrease in the concentration of plasma Lambda FLC was observed immediately upon return on Earth (R+0) in crewmembers when compared to in-flight plasma Lamnda FLC concentrations (Early: p=0.03; Mid: p=0.005 and Late/R-1: p=0.012). The preferential reduction in plasma Lambda FLC at landing without any change in plasma Kappa FLC concentration led to a minor decrease in Kappa/Lambda ratio at the Mid-flight timepoint when compared to baseline L-60/L-45 and return R+0 and R+30 / ratio (pL-45= 0.029; pR+0= 0.037; pR+18=0.053 ; pR+33=0.037). As plasma FLC levels can be impacted by altered production from plasma cells and/or impaired clearance from renal metabolism, Cystatin C was measured to calculate estimated glomerular filtration rate (eGFR) and account for variation in renal function during spaceflight. There was no change in kidney function during flight (p>0.05), however post-flight eGFR values (R+30) were significantly lower than pre-flight values (L-60/L-45) (p=0.015). Subtle changes in plasma FLC withstood adjustment for eGFR.

There was no effect of spaceflight on salivary flow rate (mL/min), and salivary Kappa FLC (mg.L) level (p<0.05). Interestingly however, reductions in salivary Lambda FLC (mg.L) levels upon return on Earth, mimicked changes observed in plasma FLC levels. As such, real-time measurement of salivary FLC could be used as a less-invasive alternative to assessing changes in immune function than plasma FLC measurements.

In conclusion, this is the first study to comprehensively show that long-duration spaceflight in human astronauts has no – or very limited – effect on plasma cell antibody output. These important results suggest that plasma immune competency is maintained in microgravity, and that future in-flight vaccine-based countermeasures are likely to be efficient at further protecting astronauts from immune dysregulation and symptomatic latent viral reactivations during prolonged exploration class missions.

A manuscript detailing the work supported by this research grant is currently under review by the Journal of Applied Physiology.

Bibliography Type: Description: (Last Updated: 02/03/2020)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Spielmann G, Campbell J, Crucian BE, Laughlin MS, Simpson RJ. "The Impact of Long Duration Spaceflight on the Function of Plasma Cells." American College of Sports Medicine 65th Annual Meeting, Minneapolis, MN, May 29-June 2, 2018.

Medicine & Science in Sports & Exercise. 2018 May;50(Suppl 1 5S):336. https://doi.org/10.1249/01.mss.0000536188.85345.86 , May-2018

Articles in Peer-reviewed Journals Spielmann G, Agha NH, Kunz HE, Simpson RJ, Crucian BE, Mehta SK, Laughlin M, Campbell J. "B-cell homeostasis is maintained during long duration spaceflight." J Appl Physiol (1985). 2019 Feb 1;126(2):469-476. Epub 2018 Nov 29. https://doi.org/10.1152/japplphysiol.00789.2018 ; PubMed PMID: 30496712; PubMed Central PMCID: PMC6397409 , Feb-2019
Project Title:  The Impact of Long Duration Spaceflight on the Function of B-cells and Biomarkers of Inflammation Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 11/01/2016  
End Date: 10/31/2017  
Task Last Updated: 08/31/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Spielmann, Guillaume  Ph.D. / Louisiana State University 
Address:  112 Long Fieldhouse 
School of Kinesiology 
Baton Rouge , LA 70803-0001 
Email: Gspielmann@lsu.edu 
Phone: 225-578-2926  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Louisiana State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Campbell, John  Ph.D. Louisiana State University and A&M College 
Crucian, Brian  Ph.D. NASA Johnson Space Center 
Laughlin, Mitzi  Ph.D. University of Houston 
Simpson, Richard  Ph.D. University of Houston 
Project Information: Grant/Contract No. NNX17AB16G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-Crew Health (FLAGSHIP, NSBRI, OMNIBUS). Appendix A-Crew Health, Appendix B-NSBRI, Appendix C-Omnibus 
Grant/Contract No.: NNX17AB16G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM07:It is necessary to correlate the observed effects of spaceflight-associated immune system dysregulation with known terrestrial clinical conditions (IRP Rev E)
Flight Assignment/Project Notes: Postflight sample analysis

Task Description: Long duration spaceflights have been associated with profound dysregulation of the immune system and latent viral reactivations, which could jeopardize crew safety and mission success. Although the clinical implications of such immune disruption have remained limited to mostly asymptomatic events, extending mission duration would increase crewmembers' risk for infection. Furthermore, the dearth of information regarding the impact of long duration spaceflight on humoral immunity and overall B-cell function raises legitimate concerns on crewmembers' ability to fight infections during a mission. It is therefore critical to extend the current knowledge on spaceflight-induced immune changes of B-cell function in order to evaluate the risks of crew adverse health events for successful implementation of future exploration-class missions. In this regard, recent scientific projects entitled “Salivary Markers” and “Integrated Immune” examined the impact of long duration spaceflight on markers of adaptive and innate immunity, but did not characterize humoral immunity and serological markers of B-cell function. The present project proposes to retrospectively analyze archived plasma and saliva samples from the aforementioned studies in order to evaluate B-cell function during and following long-duration missions. We will address the paucity of spaceflight data on B-cells by characterizing acute and chronic changes in polyclonal Free Light Chains and in Immunoglobulin class switching, indicative of a state of chronic inflammation and overall B-cell function. We will also assess if changes to these sensitive biomarkers are associated with altered risk of viral re-activation and subsequent inflammation. All assays will be performed on plasma and saliva samples previously collected from crewmembers throughout several International Space Station (ISS) missions, which will allow the studies described in this proposal to make a significant contribution to the “Salivary Markers” and “Integrated Immune” studies without the costs associated with classical flight-definition studies. On conclusion to this study we expect to have a better understanding of B-cell function during orbital flights which is essential to identify any clinical risks that may arise due to altered immunity during long-duration spaceflight missions.

Research Impact/Earth Benefits: This project will bolster our understanding of how physical and psychological stressors impact our immune system. Furthermore, this project proposes to correlate biomarkers of immune function in blood and saliva, and thus allow the use of less invasive sampling techniques (i.e., salivary swabs) to monitor immune function in special populations (children, first responders, soldiers, elderly, etc...).

Task Progress & Bibliography Information FY2018 
Task Progress: The study was initiated in November 2016 and we obtained IRB (Institutional Review Board) approval for our protocol in December 2016 and February 2017 from Louisiana State University (LSU) and NASA, respectively. In May 2017, archived serum samples from a total of 23 Astronauts (15 from the "Integrated Immune" study and 8 from the "Salivary Markers" study) along with 6 ground-based controls were de-identified by the Principal Investigators of the respective studies and transferred to our laboratory at LSU. Additionally, archived saliva samples from 8 astronauts and 6 ground-based controls were de-identified by the Principal Investigator of "Salivary Markers" study and transferred to our laboratory at LSU. All samples were stored at -80°C until analysis. Assay optimization was performed in June and July 2017 to validate our plasma and saliva assays for this project. Frozen samples are currently being analyzed for all subjects.

Publications and Presentations: The work supported by this research grant was presented at the Human Research Program Investigator’s Workshop in February 2016.

Current and Future Work: The study protocol is ongoing. By the end of year 1, we expect to have all data processed and analyzed for all crewmembers and ground-based controls. We expect to use the remainder of FY18 to interpret data, and produce scientific papers.

Applications and Acquisition of Funding: Work on this project has allowed us to apply for further research funding. We have received additional research funding from Louisiana State University to assess the impact of aerobic and resistance training on biomarkers of B-cell function and overall inflammation in patients with Type 2 diabetes. Our ideas for this project and preliminary data arose from the work performed on the present NASA project.

Bibliography Type: Description: (Last Updated: 02/03/2020)  Show Cumulative Bibliography Listing
 
 None in FY 2018
Project Title:  The Impact of Long Duration Spaceflight on the Function of B-cells and Biomarkers of Inflammation Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 11/01/2016  
End Date: 10/31/2017  
Task Last Updated: 02/07/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Spielmann, Guillaume  Ph.D. / Louisiana State University 
Address:  112 Long Fieldhouse 
School of Kinesiology 
Baton Rouge , LA 70803-0001 
Email: Gspielmann@lsu.edu 
Phone: 225-578-2926  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Louisiana State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Campbell, John  Ph.D. Louisiana State University and A&M College 
Crucian, Brian  Ph.D. NASA Johnson Space Center 
Laughlin, Mitzi  Ph.D. University of Houston 
Simpson, Richard  Ph.D. University of Houston 
Project Information: Grant/Contract No. NNX17AB16G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-Crew Health (FLAGSHIP, NSBRI, OMNIBUS). Appendix A-Crew Health, Appendix B-NSBRI, Appendix C-Omnibus 
Grant/Contract No.: NNX17AB16G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM07:It is necessary to correlate the observed effects of spaceflight-associated immune system dysregulation with known terrestrial clinical conditions (IRP Rev E)
Flight Assignment/Project Notes: Postflight sample analysis

Task Description: Long duration spaceflights have been associated with profound dysregulation of the immune system and latent viral reactivations, which could jeopardize crew safety and mission success. Although the clinical implications of such immune disruption have remained limited to mostly asymptomatic events, extending mission duration would increase crewmember’s risk for infection. Furthermore, the dearth of information regarding the impact of long duration spaceflight on humoral immunity and overall B-cell function, raises legitimate concerns on crewmembers' ability to fight infections during a mission. It is therefore critical to extend the current knowledge on spaceflight-induced immune changes of B-cell function in order to evaluate the risks of crew adverse health events for successful implementation of future exploration-class missions. In this regard, recent scientific projects entitled “Salivary Markers” and “Integrated Immune” examined the impact of long duration spaceflight on markers of adaptive and innate immunity, but did not characterize humoral immunity and serological markers of B-cell function. The present project proposes to retrospectively analyze archived plasma and saliva samples from the aforementioned studies in order to evaluate B-cell function during and following long-duration missions. We will address the paucity of spaceflight data on B-cells by characterizing acute and chronic changes in polyclonal Free Light Chains and in Immunoglobulin class switching, indicative of a state of chronic inflammation and overall B-cell function. We will also assess if changes to these sensitive biomarkers are associated with altered risk of viral re-activation and subsequent inflammation. All assays will be performed on plasma and saliva samples previously collected from crewmembers throughout several International Space Station (ISS) missions, which will allow the studies described in this proposal to make a significant contribution to the “Salivary Markers” and “Integrated Immune” studies without the costs associated with classical flight-definition studies. On conclusion to this study we expect to have a better understanding of B-cell function during orbital flights which is essential to identify any clinical risks that may arise due to altered immunity during long-duration spaceflight missions.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2017 
Task Progress: New project for FY2017.

Bibliography Type: Description: (Last Updated: 02/03/2020)  Show Cumulative Bibliography Listing
 
 None in FY 2017