Abstract
Background Exposure to high-altitude leads to two outcomes: acclimation and mal-acclimation leading to high-altitude illnesses (HAIs). Acclimation to altitude actively negates HAIs like acute mountain sickness, high-altitude pulmonary and cerebral edemas. Although HAIs have been scrutinized, acclimation has remained only empirically understood with minimal knowledge of it at molecular level in an organism. Methods In this study, we investigated (using ELISA) and statistically evaluated the trendlines of various hypoxia-responsive plasma proteins' levels, reported significantly perturbed in multiple previous studies, in individuals (male; n=20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4 and HAD7L and to 4420 m at HAD7H, HAD30 and HAD120. Findings We observed that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3) and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a capable negative control whose levels increase only in HAPE cases. We observed day and resident altitude specific proteins capable of accurately assessing acclimation when compared to baseline levels or the lower altitude zone. Interpretation The trendlines of Trx, GPx-3, Apo-AI and ST1A1 shown in this study are of acclimated individuals. These proteins have been shown to be statistically most accurate in indicating acclimation. Thus, they can serve as indicators of acclimation. A proof-of-concept protein panel is shown here which can be used to assess acclimation objectively. Funding: The study was funded by Ministry of Defence, Govt of India under Project DIP-263. Subhojit Paul is a recipient of CSIR fellowship. Anamika Gangwar is a recipient of DST-INSPIRE fellowship. Declaration of Interest: Authors declare no conflict of interest. Ethical Approval: All study protocols were cross-checked and approved by the institutional ethics committee (IEC/DIPAS/B2/1) in accordance with Helsinki declaration. Informed written consent was obtained prior to the study from all participants.
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