Trisomy 21 (Down syndrome): immune disorders
DOI: 10.32364/2587-6821-2026-10-2-4
Trisomy 21 (Down syndrome): immune disorders
A.A. Grishkina1, I.A. Tuzankina2, Ya.M. Krokhaleva1, A.V. Sulimov3, N. Xiao4
1Sverdlovsk Regional Pathology and Anatomy Bureau, Yekaterinburg, Russian Federation
2Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences,
Yekaterinburg, Russian Federation
3Children's City Clinical Hospital No. 9, Yekaterinburg, Russian Federation
4Ural Federal University named after the first President of Russia B.N. Yeltsin, Yekaterinburg, Russian Federation
Background: in addition to severe congenital malformations, predominantly involving the cardiovascular system, children with Down syndrome exhibit a high prevalence of immunodeficiency (ID). Despite the published evidence of impaired maturation and function of immune cells, as well as premature thymic involution in this population, immune system abnormalities commonly remain clinically undiagnosed.
Aim: to characterize the clinical and morphological patterns of the immune system in children with Down syndrome and to evaluate the ID detection rate across different age cohorts.
Materials and Methods: autopsy data from eight deceased children with Down syndrome were reviewed. The cohort comprised one case (12.5%) of early neonatal death, one case (12.5%) of late neonatal death, four cases (50%) of post-neonatal death, and two cases (25%) of infant death.
Results: pathological examination revealed complex congenital cardiac defects in the vast majority of children; these were accompanied by neurointestinal dysplasia of the bowel, racemose cerebrovascular angiodysplasia with focal telangiectasia, nephrocalcinosis, and bilateral renal hypoplasia. Analysis of the death causes identified Down syndrome as the principal underlying condition in seven cases (87.5%), with ID constituting an integral component of its clinical spectrum. Infectious complications served as the immediate cause of death in five cases. In two children, infectious diseases were classified as a combined condition alongside congenital malformations, having progressed in the setting of ID inherent to the chromosomal disorder. Remarkably, ID was formally documented in the final clinical diagnosis in only three (37.5%) patients. Histology of immune organs (the thymus in particular) revealed alterations in the majority of children that extended beyond a reactive response to infection, indicating profound morphofunctional insufficiency of the organ itself.
Conclusion: collectively, these findings demonstrate that the causes of death in patients with Down syndrome arise from a complex interplay among congenital structural anomalies, IDs, and, as reported in the literature, a distinctive oncological profile, the latter not being observed in the present cohort. The predominant contribution of infectious diseases to mortality highlights the critical importance of a comprehensive morphological and functional evaluation of the immune system organs, with particular emphasis on the thymus.
Keywords: immunodeficiency, trisomy 21, chromosome 21 trisomy, Down syndrome, congenital heart defects, thymus, thymic hypoplasia, lymphocytes.
For citation: Grishkina A.A., Tuzankina I.A., Krokhaleva Ya.M., Sulimov A.V., Xiao N. Trisomy 21 (Down syndrome): immune disorders. Russian Medical Inquiry. 2026;10(2):89–94 (in Russ.). DOI: 10.32364/2587-6821-2026-10-2-4
About the authors:
Anastasia A. Grishkina — C. Sc. (Med.), pathologist, Head of the Pediatric Pathology Department, Sverdlovsk Regional Pathology and Anatomy Bureau; 185a, Volgogradskaya str., Yekaterinburg, 620102, Russian Federation; ORCID iD 0000-0001-7433-2217
Irina A. Tuzankina — Dr. Sc. (Med.), Professor, Honored Scientist of the Russian Federation, Chief Freelance Pediatric Immunologist of the Ministry of Health of Sverdlovsk Region, Principal Research Scientist of the Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; 106, Pervomayskaya str., Yekaterinburg, 620078, Russian Federation; ORCID iD 0000-0001-7496-0950
Yaroslava M. Krokhaleva — Chief Freelance Specialist in Pediatric Pathology of Sverdlovsk Region, Director of the Sverdlovsk Regional Pathology and Anatomy Bureau; 185a, Volgogradskaya str., Yekaterinburg, 620102, Russian Federation; ORCID iD 0009-0003-3576-2427
Alexey V. Sulimov — C. Sc. (Med.), Chief Freelance Pediatric Neurologist of the Ministry of Health of Sverdlovsk Region, Research Specialist, neurologist at the Neurology Department, Children's City Clinical Hospital No. 9; 51, Reshetskaya str., Yekaterinburg, 620134, Russian Federation; ORCID iD 0009-0007-6459-4978
Ningkun Xiao — postgraduate student of the Department of Immunochemistry, Faculty of Chemical Engineering, Ural Federal University named after the first President of Russia B.N. Yeltsin; 19, Mira str., Yekaterinburg, 620062, Russian Federation; ORCID iD 0000-0002-0615-3222
Contact information: Anastasia A. Grishkina, e-mail: xumukyc.ru@mail.ru
Financial Disclosure: this study was performed within the framework of the state assignment of the Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences (R&D registration number NIOKTR No. 122020900136-4).
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 05.03.2026.
Revised 20.03.2026.
Accepted 27.03.2026.
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