АР19678933 Genetic screening of newborns for immunodeficiencies in Kazakhstan: a pilot study


The provision of specialized immunological care is the most significant medical problem in Kazakhstan. According to data by leading clinical immunology companies, the prevalence of primary immunodeficiencies (PID) is 2.27% of the population, associated with several factors, such as infant and child mortality, the issues with uncontrolled infectious syndrome in intensive care, purulent surgery, severe forms of tuberculosis and autoimmune pathology, oncopathology, which require huge budget expenditures.

The goal of newborn screening is the early diagnosis and successful treatment of diseases that, despite being presymptomatic, are potentially serious or fatal in infants. This will reduce the number of preventable deaths and medical costs. To screen for PID, biomarkers characterized by low or absent T- or B-cells are used: TREC, or T-cell receptor excision circle for T-cell lymphopenia and KREC, or kappa-deleting recombination excision circle for B-cell lymphopenia. They can be measured from a dry blood sample using real-time quantitative PCR. Primary immunodeficient patients with few or no T and B cells have very low or undetectable TREC or KREC copy numbers. It has been shown that a decrease in the amount of these DNA particles in a newborn heel blood sample can be used to detect severe PID.

Therefore, the idea of the project is to carry out genetic screening of newborns for immunodeficiency states based on the quantitative determination of the circular DNA regions of T-cell and B-cell receptors (TREC and KREC).

Almost all developed countries of the world have implemented these studies, as they are aware of their importance for reducing infant mortality, a significant reduction in budget expenditures. Thus, according to studies, the TREC/KREC screening assay is inexpensive, highly sensitive, and effectively integrated into public health programs. SCID is a deadly disease that imposes exorbitant costs on healthcare for every year of life. The cost of treating just one child with SCID may be more than the cost of screening for the entire population of the region. Screening with the TREC/KREC assay provides early detection and early therapy before the infant develops severe infection, organ damage, cancer, most commonly lymphoma, and ultimately death.

Also, the results of NGS sequencing will improve the early diagnosis of congenital immunodeficiency states, which will contribute to timely diagnosis and the initiation of proper treatment.

The aim

Carrying out genetic screening of newborns for immunodeficiency states based on the quantitative determination of circular DNA sections of T-cell and B-cell receptors (TREC and KREC).

Expected results

As a result of the implementation of this project, in accordance with the requirements of this tender documentation, it is expected to publish:

– at least 2 (two) articles and (or) reviews in peer-reviewed scientific editions indexed in Science Citation Index Expanded and included in the 1st (first) and (or) 2nd (second) quartile by impact factor in the Web of Science database and (or) having percentile by CiteScore in the Scopus database not less than 65 (sixty-five);

as well as at least 1 (one) article or review in a peer-reviewed foreign and domestic publication recommended by Committee for Quality Assurance in the Sphere of Education of the Ministry of Education of the Republic of Kazakhstan;

As a result of the project, data will be obtained on genetic screening of newborns for immunodeficiency conditions based on the quantitative determination of T cell receptor excision circles and kappa-deleting recombination excision circles (TREC and KREC), and genes involved in the pathogenesis of PID will be identified. The results of the work will be reported at local and international conferences.

Principal investigator

Sikhaeva Nurgul Sabyrzhanovna, PhD, H-index 6

ResearcherID Web of Science: N-4590-2017; https://orcid.org/0000-0001-6419-9483

Members of the research group

Kovzel E.F. – physician-immunologist, Doctor of medical sciences, professor, H-index 3

Scopus ID 35275267200; https://orcid.org/0000-0002-2383-0264

Morenko M.A., physician-immunologist, Doctor of medical sciences, professor

Volodchenko S., resident

Salimova A., resident

Toleuzhanova A., junior researcher

Romanova A., junior researcher.

Publications and security documents of the project manager and members of the research group

  1. Klotoe BKacimi SCosta-Conceicão EGomes HBarcellos RPanaiotov SHaj Slimene DSikhayeva NSengstake SSchuitema AAkhalaia MAlenova AZholdybayeva ETarlykov PAnthony RRefrégier GSola C. Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters. BMC Infect Dis. – 2019;19(1):553. doi: 10.1186/s12879-019-4201-2. CiteScore – 4.8, Q2
  2. Sikhayeva N., Talzhanov Y., Iskakova A., Dzharmukhanov J., Nugmanova R., Zholdybayeva E., Ramanculov E. Type 2 diabetes mellitus: distribution of genetic markers in Kazakh population. Clinical Interventions in aging (2018), 13, 377-388. doi: 10.2147/CIA.S156044. eCollection 2018., CiteScore – 5, Q1
  3. N. Sikhayeva, A. Iskakova, N. Saigi-Morgui, E. Zholdybaeva, C.-B. Eap, E. Ramanculov. Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study. BMC Medical Genetics (2017) 18:76 doi: 10.1186/s12881-017-0443-2. CiteScore – 2.3, Q3
  4. Ussenova O, Morenko M, Kovzel E, Schnaider K, Vlashenyuk K. Clinical case of stat3 gof immune dysregulation disease, ALPS. Georgian Med News. – 2020. PMID: 32965258. CiteScore – 0.3, Q3
  5. Niespodziana, Borochova K., Pazderova P. et al., Kovzel E. Toward personalization of asthma treatment according to trigger factors. J Allergy Clin Immunol. – 2020, 145(6):1529-1534. doi: 10.1016/j.jaci.2020.02.001. CiteScore – 19.7, Q1

Results achieved


An electronic database of demographic and clinical data on newborns was created and updated, including the following data: date of birth, date of sampling, ethnicity of parents, sex of the newborn, gestational age and birth weight, use of medications affecting the immune system during pregnancy or transfusion of biological materials, major and concomitant diseases of the study participant and parents. The database included newborns at risk up to 28 days of age, including premature infants with low and extremely low birth weight, newborns with severe congenital pathology and malformations, and newborns born to mothers with an aggravated obstetric history (miscarriage, stillbirths). The database of clinical data from 269 patients suffering from primary immunodeficiency in Kazakhstan was also analyzed.