Circadian and homeostatic sleep-wake regulation of secretory immunoglobulin A (sIgA): Effects of environmental light and recovery sleep

Christian Cajochen; Jakob Weber; Alejandro F Estrada; Kumpei Kobayashi; Virginie Gabel

doi:10.1016/j.bbih.2021.100394

Circadian and homeostatic sleep-wake regulation of secretory immunoglobulin A (sIgA): Effects of environmental light and recovery sleep

Brain Behav Immun Health. 2021 Nov 23:19:100394. doi: 10.1016/j.bbih.2021.100394. eCollection 2022 Feb.

Authors

Christian Cajochen^{1

2}, Jakob Weber³, Alejandro F Estrada³, Kumpei Kobayashi⁴, Virginie Gabel¹

Affiliations

¹ Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstr. 27, CH-4002, Basel, Switzerland.
² Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, CHF-4055, Basel, Switzerland.
³ NovoLytiX GmbH, Benkenstrasse 254C, CH-4108, Witterswil, Switzerland.
⁴ Development and Engineering Department, Toshiba Materials Co. Ltd, Yokohama-City, Japan.

Abstract

Secretory Immunoglobulin A (sIgA) builds the first line of the human immune defense. It is not clear whether the power of this defence line is constant across the 24-h day, depends on sleep pressure levels and can be influenced by external lighting conditions. Thus, in 10 healthy young volunteers, we retrospectively analyzed saliva samples for sIgA levels under strictly controlled laboratory conditions across 40 h of extended wakefulness under two lighting conditions (dim light 8 lx and blue-enriched light 250 lx, 9000 K) to test for circadian and homeostatic sleep-wake influences. We compared the temporal profile of sIgA with the circadian time course of melatonin and cortisol along with subjective sleepiness levels, assessed in the same study by Gabel et al. (2017). The 40-h time course of sIgA exhibited a clear circadian modulation with peak values in the mornings coinciding with the individuals' habitual rise-time. In addition, sIgA levels progressively increased throughout the 40 h of extended wakefulness and were temporally correlated with subjective sleepiness but not with subjective ratings of tension and discomfort. In contrast to the circadian profile of melatonin and cortisol, sIgA levels were not significantly altered by the lighting conditions. Unexpectedly, sIgA levels in the morning after recovery sleep from 40 h of extended wakefulness rose considerably by more than an order of magnitude (10 times more) compared to morning levels after baseline sleep. We have evidence that diurnal sIgA levels in humans are regulated by the circadian timing system, and challenging the status of the sleep-wake homeostat (i.e. extended wakefulness) boosts human sIgA levels. Thus, besides a person's circadian phase position, the first line of human immune defense also strongly depends on the person's sleep-wake history and actual sleepiness levels. In sum, the fight against pathogenic microorganisms by a key immunological component (sIgA) is modulated by two fundamental processes implicated in human sleep-wake regulation.

Keywords: Constant routine protocol; Cortisol; Cross-correlation; Enzyme-linked immunosorbent assay; Melatonin; Radioimmunoassay; Secretory IgA; Sleep pressure; Sleepiness.