Complement system activation in obstructive sleep apnea

Abstract

The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b-9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 [0-338.5] ng ml ) and in the morning (85.5 [0-247.8] ng ml ) compared with controls (30.3 [0-176.8] ng ml and 36.3 [0-167.1] ng ml , evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b-9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 [1.6-47.4] ng ml to 9.3 [0-46.4] ng ml , p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C-reactive protein and low high-density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

“…Inpatient polysomnography and cardiorespiratory polygraphy were performed as described previously [2][3][4] using Somnoscreen Plus Tele PSG (Somnomedics GMBH Germany). Sleep stages, movements and cardiopulmonary events were scored manually according to the American Academy of Sleep Medicine [24] guidelines.…”

“…Chronic intermittent hypoxia and increased sympathetic tone induce production of pro-inflammatory molecules, such as interleukin (IL)-6, IL-1β, tumour necrosis factor-α [1] or complement elements [2] and suppresses the release of anti-inflammatory [3,4] molecules. Linked to inflammation and sympathetic activity, OSA is characterised by a hypercoagulation state [5][6][7][8][9].…”

Circadian Clock and Complement Immune System—Complementary Control of Physiology and Pathology?

“…Using a mouse model devoid of C5 complement signaling, rhythmic HPSC recruitment could be entirely blocked, implicating the importance of circadian complement pathway activation in immune surveillance (Massberg et al, 2007;Janowska-Wieczorek et al, 2012;Ratajczak et al, 2012;Budkowska et al, 2018). While this study implicates rhythmic complement activation in the context of circulating HPSCs, other studies have shown a sleep-dependent increases in C3, C4, C3a, C5a, and complement factor I (CFI) ultimately resulting in dysregulated cytokines production (Reis et al, 2011;Manzar et al, 2016;Horvath et al, 2018;Wadhwa et al, 2019). Using the Pittsburgh Sleep Quality Index (PSQI) in a relatively small number of male university students, Manzar et al demonstrated that poor sleep quality correlates with decreased proinflammatory C3 and C4 in the serum and increased levels of anti-inflammatory CFI during early bedtime and daytime (Manzar et al, 2015), suggesting that regular sleep patterns may be important for the normal cycling of complement factors.…”

“…Using the Pittsburgh Sleep Quality Index (PSQI) in a relatively small number of male university students, Manzar et al demonstrated that poor sleep quality correlates with decreased proinflammatory C3 and C4 in the serum and increased levels of anti-inflammatory CFI during early bedtime and daytime (Manzar et al, 2015), suggesting that regular sleep patterns may be important for the normal cycling of complement factors. Supporting this link, increased serum C3a levels in both evening and daytime was correlated with severity of obstructive sleep apnea (Horvath et al, 2018). Under optimal physiological conditions, complement regulatory factors including CR1, membrane cofactor protein (MCP; also known as CD46), and Factor H control the complement activation at the levels of C3 convertase and inhibit the formation of C5-C9 MAC that could be detrimental to host cells.…”

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea

“…Full-night cardiorespiratory polygraphy and polysomnography were performed using the Somnoscreen Plus Tele PSG (Somnomedics GmbH Germany) as described previously 49 . Sleep stages, movements and cardiopulmonary events were scored manually according to the American Academy of Sleep Medicine (AASM) guideline 50 .…”