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

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.

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.

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.