Factors associated with variability of the course of X-linked agammaglobulinemia

Abstract

Introduction. Historically the development of a section of clinical immunology dedicated to the problem of primary immunodeficiencies (PID) has begun with X-linked agammaglobulinemia (XLA). Despite numerous studies and achievements in the diagnosis and treatment of XLA, not all the problems associated with the management of patients with this variant of PID have been resolved. Evidence of Btk effect on the functions of not only B lymphocytes, but also other components of the immune system determines interest for the complex characterization of cellular factors of the innate and adaptive immune response.

The aim of the study was to determine the changes in the cellular parameters of the immune response and their dynamics depending on the duration and severity of the course of X-linked agammaglobulinemia.

Material and methods. 12 patients with XLA were under dynamic observation. ВТК genetic defect confirmed using next generation sequencing technology. In immunological monitoring, methods were used to assess the quantitative and functional parameters of the factors of innate and adaptive immunity.

Results. The results indicate that in patients with XLA, the processes of maturation and cytotoxicity of T-effectors are enhanced with inhibition of immunoregulatory suppression, neutrophil microbicidal activity, and natural killer cytotoxicity. It was shown that a more severe course is associated with a more significant inhibition of neutrophil metabolism; an increase in the experience of the disease is associated with an increase in the number of T-effectors, a decrease in the cytolytic potentials of natural killers.

Conclusion. The obtained results undoubtedly require further study in a larger cohort of patients. Nevertheless, data on the quality and degree of involvement of the cellular components of the immune response should be considered when managing patients with XLA in daily practice.

Keywords:primary immunodeficiency; humoral PID; X-linked agammaglobulinemia

For citation: Sizyakina L.P, Andreeva I.I., Danilova D.I. Factors associated with variability of the course of X-linked agammaglobulinemia. Immunologiya. 2020; 41 (6): 550-6. DOI: https://www.doi.org/10.33029/0206-4952-2020-41-6-550-556 (in Russian)

Funding. The work was performed under state task, state registration number АААА-А18-118013090213-5.

Conflict of interests. The authors declare no conflict of interests.

References

1. Bruton O.C. Agammaglobulinemia. Pediatriсs. 1952; 9 (6): 722–8.

2. Durandy A., KraCker S., FisCher A. Primary antibody deficiencies. Nat. Rev. Immunol. 2013; 13 (7): 519–33.

3. Kuz’menko N.B., Shcherbina A.Yu. Classification of primary immunodeficiencies as a reflection of modern ideas about their pathogenesis and therapeutic approaches. Rossiyskiy zhurnal detskoy gematologii i onkologii. 2017; 4 (3): 51–7. (in Russian)

4. Tangye S.G., Al-Herz W., Bousfiha A., et al. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 2020. URL: https://doi.org/10.1007/s10875-019-00737

5. Chen X.F. Wang W.-F., Zhang Y.-D., et al. Clinical Characteristics and genetic profiles of 174 patients with X-linked agammaglobulinemia: report from Shanghai, China (2000–2015) [Electronic resource]. Medicine. 2016; 95 (32): e4544. DOI: http://dx.doi.org/10.1097/MD.0000000000004544 (date of access August 12, 2019)

6. Latysheva E.A., Latysheva T.V., Pashchenkov M.V. Primary immunodeficiencies in adults - an analysis of the register of the Institute of Immunology. Rossiyskiy allergologicheskiy zhurnal. 2018; 15 (9): 17–26. (in Russian)

7. Khaitov R.M., Il’yina N.I. Clinical Immunology and Allergology: Federal Clinical Guidelines. Moscow: Farmus Print Media, 2015. (in Russian)

8. Amaya-Uribe L., Rojas M., Azizi G., et al. Primary immunodeficiency and autoimmunity: a comprehensive review. J. Autoimmun. 2019; 99: 52–72.

9. Aguilar C. Malphettes M., Donadieu J., et al. Prevention of infections during primary immunodeficiency. Clin. Infect. Dis. 2014; 59 (10): 1462–70.

10. Shillitoe B., Gennery A. X-linked agammaglobulinaemia: outcomes in the modern era. Clin. Immunol. 2017; 183: 54–62.

11. Sizyakina L.P., Andreeva I.I., Krolevets D.I. Functional activity of cellular factors of innate immunity in primary agammaglobulinemia. Immunologiya. 2017; 38 (4): 223–6. (in Russian)

12. Al-Mousa H., Abouelhoda M., Monies D.M., et al. Unbiased targeted next-generation sequenсing molecular approach for primary immunodeficiency diseases. J. Allergy Clin. Immunol. 2016; 137 (6): 1780–7.

13. Gallo V., Dotta L., Giardino G., et al. Diagnostics of primary immunodeficiencies through next-generation sequencing [Electronic resource]. Front. Immunol. 2016; 7 (7): 466. URL: http://dx.doi.org/10.3389/fimmu.2016.00466

14. Khaitov R.M., Pinegin B.V., Yarilin A.A. Guidelines for Clinical Immunology. Diagnosis of Diseases of the Immune System: a guide for doctors. Moscow: GEOTAR-Media; 2009. (in Russian)

15. Qin X., Jiang L.-P., Tang X.-M., et al. Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients. World J. Pediatr. 2013; 9 (3): 273–7.

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