ORIGINAL ARTICLE Plasma protein(s)–based conceptual diagnostic tool for assessing high-altitude acclimation in humans Subhojit Paul 1 & Anamika Gangwar 1 & Kalpana Bhargava 1 & Nilofar Khan 1 & Pankaj Khurana 1 & Yasmin Ahmad 1 Received: 12 April 2019 /Revised: 30 July 2019 /Accepted: 20 August 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Exposure to high altitude above 3000 m leads to two outcomes—acclimation or high-altitude maladies. To reach a particular outcome, the plasma proteome is modified differentially, either in context of an acclimation response or mal-acclimation response leading to disease. This ensures that hypoxia-responsive plasma protein trends reflect acclimation in acclimated individuals when compared with their levels prior to acclimation. Such protein trends could be used to assess acclimation in an individual and any significant deviation from this trend may indicate non-acclimation, thereby preventing high-altitude illnesses before they man- ifest. In this study, we investigate and statistically evaluate the trendlines of various hypoxia-responsive plasma protein levels, reported significantly perturbed in our 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. We observe 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 cases of HAPE. We also observe exposure day-specific and resident altitude-specific proteins capable of accurately assessing acclimation when compared with baseline levels or the lower altitude zone. Keywords High-altitude . Acclimation . Plasma proteins . Biomarkers . Diagnostic . Calcium signaling Introduction High-altitude acclimation, although essential for safe ascent till below the death zone (> 7500 m), has received insufficient scientific scrutiny to comprehend the trends of various pro- teins of diagnostic value in the proteome during chronic ex- posure to high-altitude conditions. High-altitude acclimation fundamentally depends on two factors: duration and altitude of exposure. Although it has received scarce scientific scruti- ny, it’ s the most crucial aspect to high-altitude exploration. Acclimation status assessment at altitude has never been given thorough objective analysis. In the general populace, acclimation assessment is based on an individual deciding whether one should ascend higher within a stipulated time (Karinen et al. 2008). In the Armed forces, acclimation assess- ment is based on finishing physical tasks at the end of a fixed exposure duration before ascending further (Deshwal et al. 2012; Syed et al. 2010). The current acclimation process (for Indian Army) requires at least 10 days of continuous high- altitude exposure with incremental ascents every 5th day in- corporating both factors, duration and altitude. The acclimati- zation process at its core aims to make individuals tolerant to the ambient hypobaric hypoxia. However, all preliminary di- agnostic foci for assessment of acclimatization are limited to subjective physical symptoms. Poor acclimation causes high- altitude maladies like acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) (Ren et al. 2010). Even though these diseases themselves have received wide scientific interest, the process of objectively assessing accli- mation has not evolved much. During ascent, if a person is suspected to have AMS, he/she is asked to fill a Lake Louise questionnaire, marking themselves for symptoms like nausea, fatigue, and headache. Even in case of more severe HAPE, initial diagnosis is limited to benign parameters like difficulty Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10142-019-00712-0) contains supplementary material, which is available to authorized users. * Yasmin Ahmad yasminchem@gmail.com 1 Defence R&D Organization (DRDO), Defence Institute of Physiology & Allied Sciences (DIPAS), Lucknow Road, Timarpur, New Delhi 110054, India Functional & Integrative Genomics https://doi.org/10.1007/s10142-019-00712-0