Features of proteomic profi le of blood serum of children with bronchial asthma who underwent perinatal central nervous system damage

Objective: proteomic analysis of blood serum of children with bronchial asthma with a history of indication of the pathology of the perinatal period.

Materials and methods: a comprehensive examination of children suffering from asthma and patients of the control group using proteomic analysis of blood serum was carried out. Proteomic analysis of blood serum was performed using two-dimensional high-resolution gel electrophoresis followed by staining of gels with fl uorescent dye and time-of-fl ight MALDI mass spectrometry. The proteins were identifi ed using Mascot MS peptide fi ngerprint analysis algorithm and Swiss-Prot protein database.

Results: comparative analysis of the proteomic profi le of blood serum of children with pathology of the central nervous system in the perinatal period and developed in the subsequent bronchial asthma and control group patients allowed to establish that number proteins products were reduced in this disease. The proteins in the molecular mass range 16-33 kDa (p<0.05) were identifi ed: glutathione peroxidase 3, transthyretin and system components compliment С4В and C3.

Conclusion: modifi cation of the production of these proteins indicates the presence of damage at the molecular level, leading to metabolic and functional disorders in the body of a patient with asthma having a history of indicating the pathology of the perinatal period. 

1. Trepilec SV, Golosnaya GS, Trepilec VM, Kukushkin EI. Hypoxic hemorrhagic brain lesions in neonates: the significance of determination of neurochemical markers, inflammation markers and apoptosis in the neonatal period and catamnesis follow-up results. Pediatriya. 2018;97(1):31-37. (In Russ).

2. Krasnoruckaya ON, Ledneva VS. Clinical and biochemical indices in diagnosis of developmental disorders in children with consequences of perinatal lesion of the nervous system. Pediatriya named after G. N. Speransky. 2018;97(3):175-179. (In Russ).

3. SHnitkova EV, Filosofova MS, CHemodanov VV, Sokolova SV, Pronina II, Baldaev AA. Osobennosti ontogeneticheskogo razvitiya detej, perenesshih perinatal’nuyu gipoksiyu. Vestnik Ivanovskoj medicinskoj akademii. 2007;12(3-4):194- 195. (In Russ).

4. Pavlenko VA, Mel’nikova IM, Mizernickij YUL. The prognostic significance of functional parameters of the respiratory system and autonomic nervous system in infants with a history of acute obstructive bronchitis against the background of perinatal lesion of the central nervous system. Voprosy prakticheskoj pediatrii. 2015;10(1):7-14. (In Russ).

5. National program “Bronchial asthma in children. Th e strategy of treatment and prevention “5th ed., Corr. and add. M .: Izd. House “Atmosphere”; 2017. (In Russ).

6. Görg A, Boguth G, Obermaier C, Posch A, Weiss W. Two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimension (IPG-Dalt): the state of the art and the controversy of vertical versus horizontal systems. Electrophoresis. 1995;16:1079-1086. DOI: 10.1002/elps.11501601183

7. Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins from silver stained polyacrylamide gels. Anal Chem. 1996;68:850-858. DOI: 10.1021/ac950914h

8. Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2010;12(1):93-124. doi: 10.1089/ARS.2008.2425.

9. Polonikov AV, Ivanov VP, Bogomazov AD, Solodilova MA. Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma. Biomeditsinskaya khimiya. 2015;61(4):427-439. (In Russ). Doi: 10.1134/S1990750814040076

10. Nikitin A.V., Zolotareva M.A. The role of the enzyme activity in formation of oxidative stress in the patients with bronchial asthma (review). Vestnik novyh medicinskih tekhnologij. 2013;HX(2):165-169. (In Russ).

11. Youness ER, Shady M, Nassar MS, Mostafa R, Abuelhamd W. The role of serum nuclear factor erythroid 2-related factor 2 in childhood bronchial asthma. J Asthma. 2019:1-6. doi: 10.1080/02770903.2019.1571081.

12. Ben Anes A, Ben Nasr H, Fetoui H, Bchir S., Chahdoura H, et al. Alteration in systemic markers of oxidative and antioxidative status in Tunisian patients with asthma: relationships with clinical severity and airfl ow limitation. J Asthma. 2016;53(3):227-37. doi: 10.3109/02770903.2015.1087559.

13. Youness ER, Shady M,. Nassar MS, Rehab M, Walaa Ab. The role of serum nuclear factor erythroid 2-relatedfactor 2 in childhood bronchial asthma. Journal of Asthma. 2019 7:1-6. doi:10.1080/02770903.2019.1571081

14. Liz MA, Faro CJ, Saraiva MJ, Sousa MM. Transthyretin, a new cryptic protease. J Biol Chem. 2004;279(20):21431-8. DOI: 10.1074/jbc.M402212200

15. Berry DC, Croniger CM, Ghyselinck NB, Noy N. Transthyretin blocks retinol uptake and cell signaling by the holo-retinol-binding protein receptor STRA6. Mol Cell Biol. 2012;32(19):3851-9. doi: 10.1128/MCB.00775-12.

16. Ejaz S, Nasim FU, Ashraf M, Ahmad S. Serum Proteome Profiling to Identify Proteins Promoting Pathogenesis of Nonatopic Asthma. Protein Pept Lett. 2018;25(10):933-942. doi: 10.2174/0929866525666180925142119.

17. Mehrani H, Ghanei M, Aslani J, Golmanesh L. Bronchoalveolar lavage fluid proteomic patterns of sulfur mustard-exposed patients. Proteomics Clin Appl. 2009;3(10):1191-200. doi: 10.1002/prca.200900001.

18. Karimova HM, Namazova-Baranova LS, Klyushnik TP, Mamed”yarov AM. Prognosticheskoe znachenie pokazatelej vrozhdennogo immuniteta u detej s posledstviyami perinatal’nogo porazheniya CNS gipoksicheski-ishemicheskogo geneza. Praktika pediatra. 2012;3:6-12. (In Russ).

19. Marc MM, Korosec P, Kosnik M, Kern I, Flezar M, et al. Complement Factors C3a, C4a, and C5a in Chronic Obstructive Pulmonary Disease and Asthma. J. Respir. Cell Mol. Biol. 2004;31:216–219. doi: 10.1165/rcmb.2003-0394OC.

20. Morozov SG, Kozhevnikova EN, Petkevich NP, Inshakova VM, Kluyshnik TP, Sidyakin AA. Nejroimmunnyj status detej s perinatal’noj patologiej nervnoj sistemy. Voprosy ginekologii, akusherstva i perinatologii. 2014;13(5):33-39. (In Russ).

21. Sozaeva DI, Berezhanskaya SB. The role of immunocytokines in the genesis of cerebral ischemia in newborns from the group of high perinatal risk. Kubanskij nauchnyj medicinskij vestnik. 2011;2(125):151-155. (In Russ).