LEVELS OF AUTOANTIBODIES AGAINST DOPAMINE AND NMDA RECEPTORS IN CHILDREN DEPENDING ON THE SEVERITY OF DIABETIC KETOACIDOSIS

The aim of the research. To measure and analyze the levels of autoantibodies (AAB) against dopamine and NMDA receptors in children in relation to the severity of diabetic ketoacidosis (DKA).

Materials and methods. The study included 76 children, of which 38 children (study group) had type 1 diabetes mellitus (DM) and diabetic ketoacidosis (DKA) and 38 were apparently healthy children (control group). The study group children were divided into three subgroups: grade 1 DKA (n=22); grade 2 DKA (n=12); and grade 3 DKA (n=4). Blood serum samples were analyzed to measure the levels of AAB to type 2 dopamine receptors (DAR2) and type 1 glutamatergic receptors (NMDAR1). Statistical data were processed using the Mann-Whitney test, Kruskel-Wallis test, and Spearman's rank correlation coefficient. The statistical significance level was specified as p<0.05.

Results. The largest clinical impairments in the level of consciousness and biochemical parameters were discovered in children with grade 3 DKA. All patients with DKA had elevated mean levels of AAB against both NMDAR1, amounting to 3.82 [3.0-5.59] U/mL compared with 1.12 [0.65-1.64] U/mL (p=0.000) in apparently healthy children, and DAR2, amounting to 7.24 [3.84-12.19] U/mL compared with 2.13 [1.45-3.15] U/mL (p=0.000) in the control group patients. The elevation of the levels of AAB against NMDAR1 and DAR2 was discovered to depend on the clinical severity of DKA (with the maximal concentrations found in grade 3 DKA). A correlation was shown to exist between elevated levels of AAB and consciousness impairments.

Conclusion. The obtained results indicate the impairment of the glutamatergic and dopaminergic systems in DKA in children with type 1 DM, which points at the presence of brain dysfunction.

1. Chiarelli F., Rewers M., Phillip M. Screening of Islet Autoantibodies for Children in the General Population: a Position Statement endorsed by the European Society for Pediatric Endocrinology. Horm Res Paediatr. 2022. DOI: 10.1159/000525824. Online ahead of print.

2. Pasi R., Ravi K.S. Type 1 diabetes mellitus in pediatric age group: A rising endemic. J Family Med Prim Care. 2022. 11(1). 27-31. DOI: 10.4103/jfmpc.jfmpc_975_21

3. Raghunathan V., Jevalikar G., Dhaliwal M., Singh D., Sethi S.K., Kaur P., Singhi S.C. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med. 2021. 25(12). 1446-1451. DOI: 10.5005/jp-journals-10071-24038

4. Baszyńska-Wilk M., Wysocka-Mincewicz M., Wajda-Cuszlag M., Świercz A., Szalecki M. Letter to the Editor: Central Nervous System Complications in Diabetic Ketoacidosis. Pediatr Endocrinol Rev. 2019. 17(1):47-49. DOI: 10.17458/per.vol17.2019.le.bwwmwc. nervouscomplicationsdiabetic.

5. Gardoni F., Stanic J., Scheggia D., Benussi A., Borroni B., Di Luca M. NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features. Cells. 2021. 10(1). 77. DOI: 10.3390/cells10010077

6. Arinuma Y. Antibodies and the brain: anti-N-methyl-D-aspartate receptor antibody and the clinical effects in patients with systemic lupus erythematosus. Curr Opin Neurol. 2018. 31(3). 294-299. DOI: 10.1097/WCO.0000000000000554

7. Klein M.O., Battagello D.S., Cardoso A.R., Hauser D.N., Bittencourt J.C., Correa R.G. Dopamine: Functions, Signaling, and Association with Neurological Diseases. Cell Mol Neurobiol. 2019. 39(1). 31-59. DOI: 10.1007/s10571-018-0632-3

8. Dale R.C., Merheb V., Pillai S., Wang D., Cantrill L., Murphy T.K., Ben-Pazi H., Varadkar S., Aumann T.D., Horne M.K., Church A.J., Fath T., Brilot F. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012. 135(11). 3453-68. DOI: 10.1093/brain/aws256

9. Bykov Yu.V., Baturin V.A., Uglova T.A. Estimating the levels of autoantibodies to NMDA and dopamine receptors in children with diabetes mellitus type I, subject to the condition severity. Medicine. 2020. 8(2). 73-80. in Russian. DOI: 10.29234/2308-9113-2020-8-2-73-80

10. Federal clinical guidelines (protocols) for the management of children with endocrine diseases. Edited by I.I. Dedov and V.A. Peterkova. M. Praktika. 2014. 442. in Russian.

11. Hanas R., Donaghue K.C., Klingensmith G., Swift P.G. ISPAD clinical practice consensus guidelines 2009 compendium. Introduction. Pediatr Diabetes. 2009. 10(12). 1-2. DOI: 10.1111/j.1399-5448.2009.00577.x

12. Braine M.E., Cook N. The Glasgow Coma Scale and evidence-informed practice: a critical review of where we are and where we need to be. J Clin Nurs. 2017. 26(1-2). 280-293. DOI: 10.1111/jocn.13390

13. Algorithms of specialized medical care for patients with diabetes mellitus. Edited by I.I. Dedov, M.V. Shestakova, A.Yu. Mayorov. 10th issue (expanded). M. 2021. in Russian. DOI: 10.14341/DM12802

14. Burcul I., Arambasic N., Polic B., Kovacevic T., Bartulovic I., Catipovic Ardalic T., Markic J. Medicina (Kaunas). Characteristics of Children with Diabetic Ketoacidosis Treated in Pediatric Intensive Care Unit: Two-Center Cross-Sectional Study in Croatia. 2019. 55(7). 362. DOI: 10.3390/medicina55070362