Significance of immunological markers in patients with obstructive sleep apnea and comorbid pathology

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OBJECTIVE

To determine the significance of immunological markers in patients with obstructive sleep apnea (OSA) and comorbid pathology.

MATERIAL AND METHODS

Sixty-five patients were examined. Two groups of patients were distinguished: the main group with moderate and severe OSA and the control group without OSA. The subjects underwent anthropometry, polysomnography, assessment of cognitive and emotional disorders. Glial fibrillar acidic protein (GFAP), antibodies against NR1-NR2 subunits of NMDA receptors (AT to GRIN2A) and the acetylcholine receptor (AT to AChR), and brain-derived neurotrophic factor (BDNF) were studied by enzyme immunoassay.

RESULTS

In patients with OSA, indicators of markers: GFAP (p=0.017), BDNF (p=0.006), antibodies to AChR (p=0.002), as well as chronic cerebral ischemia (p=0.000), depression on the HADS (p=0.004) and the Beck scale (p=0.000), drowsiness on the Epworth scale (p=0.001), asthenia on the visual analogue scale (p=0.000) and the MFI 20 (p=0.013) were higher than in the control group. A relationship was established in the main group between the identified subjective disorders on the Mini-Mental State Examination scale (MMSE) and BDNF (r=0.302, p=0.014) and the average score on the MMSE and BDNF (r=–0.266, p=0.032).

CONCLUSION

The results demonstrate the relationship of neurospecific proteins with cognitive impairment in patients with OSA. The neuromarker GFAP in patients with sleep apnea has shown itself to be a predictor of decreased neurogenesis, and BDNF as a representative marker of neuroplasticity. Large values of AT to AChR in patients with OSA may indicate possible neuromuscular transmission disorders. Along with drowsiness and asthenia, patients with OSA have changes in the emotional background, mainly due to depression. The severity of depression and the severity of asthenia increase with increasing severity of apnea and are probably associated with low levels of saturation, which in turn leads to dysregulation of the prefrontal cortex, hippocampus and amygdala.

Keywords:

obstructive sleep apnea

chronic cerebral ischemia

brain-derived neurotrophic factor

glial fibrillar acidic protein

antibodies to the NR2 subunit of NMDA

antibodies to the acetylcholine receptor

Authors:

Rubina S.S.

Tver State Medical University

ORCID: 0000-0003-3804-6998

Chichanovskaya L.V.

Tver State Medical University

ORCID: 0000-0002-3808-4866

Makarova I.I.

Tver State Medical University

ORCID: 0000-0002-0297-3389

Slusar N.N.

Tver State Medical University

ORCID: 0000-0001-7865-0984

Received:

06.09.2023

Accepted:

23.04.2024

List of references:

Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Am Rev Med. 1976;27:465-484.
Tishkevich ES, Kolyadich ZhV. Risk factors for obstructive sleep apnea syndrome. Otorinolaringologiya. Vostochnaya Evropa. 2020;10(2):96-102. (In Russ.).
Agaltsov MV, Drapkina OM. Obstructive sleep apnea and cardiovascular comorbidity: common pathophysiological mechanisms. Ratsional’naya Farmakoterapiya v Kardiologii. 2021;17(4):594-605. (In Russ.). https://doi.org/10.20996/1819-6446-2021-08-05
Rubina SS, Makarova II. Obstructive sleep apnea: a modern view of the problem. Ural’skii Meditsinskii Zhurnal. 2021;20(4):85-92. (In Russ.). https://doi.org/10.52420/2071-5943-2021-20-4-85-92
Yashchenko AV, Kamaev YuO. The risk of developing cognitive impairment in patients with obstructive sleep apnea syndrome. Vestnik Psikhofiziologii. 2018;(3):128-132. (In Russ.).
Kemstach VV, Korostovtseva LS, Golovkova-Kucheryavaya MS, et al. Obstructive sleep apnea syndrome and cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(1):90-95. (In Russ.). https://doi.org/10.17116/jnevro202012001190
DeZee KJ, Hatzigeorgiou C, Kristo D, et al. Prevalence of and screening for mental disorders in a sleep clinic. J Clin Sleep Med. 2005;1(2):136-142.
Palman AD. Obstruktivnoe apnoe sna. M.: GEOTAR-Media; 2020. (In Russ.). https://doi.org/10.33029/9704-5717-7-APN-2020-1-112
Rubina SS, Makarova II, Ignatova YuP, et al. Features of heart rate variability in patients with obstructive sleep apnea and comorbid pathology in neurological practice. Ural’skii Meditsinskii Zhurnal. 2022;21(4):4-12. (In Russ.).
Bianchi R, Garbuglia M, Verzini M, et al. S100 protein and annexin II2- pl12 (calpactin I) act in concert to regulate the state of assembly of GFAP intermediate filaments in vitro. Biochem. Biophys. Res. Commun. 1995;208(3):910-918.
Brenner M. Structure and transcriptional regulation of GFAP gene. Brain Pathol. 1994;4:245-257.
Pavlov KA, Gurina OI, Dmitrieva TB, et al. Development of a GFAP enzyme immunoassay based on a recombinant antigen. Byul. Eksperim. Biologii i Meditsiny. 2008;146(11):535-540. (In Russ.).
Thaler JP, Yi Ch-X, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122(1):153-162. https://doi.org/10.1172/JCI59660
Benedet AL, Milà-Alomà M, Vrillon A, et al. Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum. JAMA Neurol. 2021;78(12):1471-1483. https://doi.org/10.1001/jamaneurol.2021.3671
Krasnov AV. Astrocyte proteins of the brain: structure, functions, clinical significance. Neironauka i Klinicheskaya Nevrologiya. 2012;17(1):37-42. (In Russ.).
Chekhonin VP, Dmitrieva TB, Zhirkov YuA. Immunokhimicheskii analiz neirospetsificheskikh antigenov. M. 2000. (In Russ.).
Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets. 2013;14(11):1225-1236. https://doi.org/10.2174/13894501113149990156
Semenov DG, Belyakov AV. BDNF and senile cognitive depression. Zhurnal Vysshei Nervnoi Deyatel’nosti. 2021;71(4):453-467. (In Russ.). https://doi.org/10.31857/S0044467721040079
Pöyhönen S, Er S, Domanskyi A, Airavaara M. Effects of neurotrophic factors in glial cells in the central nervous system: Expression and properties in neurodegeneration and injury. Front Physiol. 2019;10(APR):1-20. https://doi.org/10.3389/fphys.2019.00486
Flores KR, Viccaro F, Aquilini M, et al. Protective role of brain derived neurotrophic factor (BDNF) in obstructive sleep apnea syndrome (OSAS) patients. PLoS One. 2020;15(1):1-11. https://doi.org/10.1371/journal.pone.0227834
Shepeleva II, Chekhonin IV, Chernysheva AA, et al. The role of the brain-derived neurotrophic factor in the pathogenesis of depressive disorders. Molekulyarnaya Meditsina. 2021;19(3):8-16. (In Russ.). https://doi.org/10.29296/24999490-2021-03-02
Schröter K, Brum M, Brunkhorst-Kanaan N, et al. Longitudinal multi-level biomarker analysis of BDNF in major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2020;270(2):169-181. https://doi.org/10.1007/s00406-019-01007-y
Ursitti F, Roberto D, Papetti L, et al. Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge. Eur. J Paediatr Neurol. 2021;30:9-16. https://doi.org/10.1016/j.ejpn.2020.12.004
Dalmau J, Tuzun E, Wu H, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61(1):25-36. https://doi.org/10.1002/ana.21050
Wang R, Reddy PH. Role of Glutamate and NMDA Receptors in Alzheimer’s Disease. J Alzheimers Dis. 2017;57(4):1041-1048. https://doi.org/10.3233/JAD-160763
Wenke NK, Kreye J, Andrzejak E, et al. N-methyl-D-aspartate receptor dysfunction by unmutated human antibodies against the NR1 subunit. Annals of Neurology. 2019;85(5):771-776.
Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990;185(1):1-10. https://doi.org/10.1016/0014-2999(90)90204-j
Lener MS, Niciu MJ, Ballard ED, et al. Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine. Biol Psychiatry. 2017;81(10):886-897. https://doi.org/10.1016/j.biopsych.2016.05.005
Sanadze AG. Miasteniya i miastenicheskie sindromy. M.: Litera; 2012. (In Russ.).
Makarina-Kibak LE, Kolyadich ZhV, Zatoloka DA, et al. Results of the soft palate implantation method for the treatment of snoring and obstructive sleep apnea syndrome. Otorinolaringologiya. Vostochnaya Evropa. 2012;2(07):91-98. (In Russ.).
Kulesh AA, Emelin AYu, Bogolepova AN, et al. Clinical manifestations and issues of diagnosis of chronic cerebrovascular disease [chronic cerebral ischemia] at an early [predemental] stage. Nevrologiya, Neiropsikhiatriya, Psikhosomatika. 2021;13(1):4-12. (In Russ.). https://doi.org/10.14412/2074-2711-2021-1-4-12
Epstein LJ, Kristo D, Strollo PJJr, et al. Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263-276.
American Academy of Sleep Medicine Task Force. Sleeprelated breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999;22(5):667-689.
Zakharov VV, Voznesenskaya TG. Nervno-psikhicheskie narusheniya: diagnosticheskie testy. 2-e izd. M.: MEDpress-inform; 2013. (In Russ.).
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545.
Smets EM, Garssen B, Bonke B, et al. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995;39(3):315-325.
Piotrowski C. Co-Morbidity of Sleep Disorders in Veterans with PTSD: An Integrated Synopsis of 109 Studies (1995-2020). SIS Journal of Projective Psychology & Mental Health. 2020;27(2):83-97.
Semchenko VV, Stepanov SS, Bogolepov NN. Sinapticheskaya plastichnost’ golovnogo mozga (fundamental’nye i prikladnye aspekty). Omsk, Omsk Regional Printing House; 2008. (In Russ.).
Schwarz EI, Furian M, Schlatzer C, et al. Nocturnal cerebral hypoxia in obstructive sleep apnea: a randomised controlled trial. Eur Respir J. 2018;51:1800032. https://doi.org/10.1183/13993003.00032-2018

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