Age-determined dynamics of T-lymphocyte subpopulations in patients with 22q11.2 deletion syndrome (DiGeorge syndrome)
Authors: Davydova N.V. ,   G.N. Speransky City Children’s Hospital No. 9, Moscow, Russia, Zinovyeva N.V. , Zimin S.B. , Shvets O.V. , Galeeva E.V. , Korsunskiy I.A. , Prodeus A.P. , Gildeeva G.N. , Kozlov I.G. ,   G.N. Speransky City Children’s Hospital No. 9, Moscow, Russia,   Morozov Children’s City Clinical Hospital, Moscow, Russia,   Polyclinic No. 3 of the “Family Physician” Moscow City-based Network of Private Clinics, Moscow, Russia,   G.N. Speransky City Children’s Hospital No. 9, Moscow, Russia,   HaEmek Medical Center, Afula, Jezreel Valley, Northern District, Israel,   G.N. Speransky City Children’s Hospital No. 9, Moscow, Russia,   I.M. Sechenov First Moscow State Medical University, Moscow, Russia,   I.M. Sechenov First Moscow State Medical University, Moscow, Russia
Published: August 2024

Patients with the 22q11.2 deletion syndrome (DiGeorge syndrome, DDS) suffer from T-cell lymphopenia, changes in function and subpopulation of T-lymphocytes. The bibliographical data conflicts on the characteristics of T-lymphocytes in patients with DDS and their changes during physiological maturation. The purpose of this research was to follow-up patients with emphasis on the dynamics of changes in T-lymphocyte subpopulations with age. Methods used: 117 patients observed during 2013-2023 who were administered at the Allergology and Immunology Department with the G.N. Speransky City Children’s Hospital No. 9 (Moscow, Russia) with a diagnosis of DDS and who had undergone blood sampling to assess T-lymphocyte subpopulations using flow cytometry. All patients (0 to 18 y/o) were divided into 4 age groups: 0 to 2 y/o, 2 to 5 y/o, 5 to 10 y/o and 10 to 18 y/o. In parallel, the blood samples of 185 apparently healthy children of the corresponding age were examined. Results: a decrease in CD3 T-lymphocytes, CD4 T-helper cells, CD8 T-cytotoxic lymphocytes, CD4 early thymic emigrants and CD4 naive T-lymphocytes was found in all age groups (p<0.05). CD8+ naive T-lymphocytes and CD8+ early thymic emigrants were reduced in all age groups, but in the 2 to 5 y/o age group their values were close to normal (p=0.072 and p=0.220, respectively). CD4+ central memory cells were elevated in all age groups (p<0.001), while CD8+ central memory cells, CD4+ and CD8+ effector memory cells differed in that they had normal values in the 2 to 5 y/o age group (p=0.229, p=0.457 and p=0.140, respectively). CD4+ TEMRA were significantly increased in the 0 to 2 y/o age group (p=0.002), and in older age groups they tended to normal values. CD8+ TEMRA did not differ from the control group and did not have age-related dynamics. The T-helper subpopulations were characterized by a significant increase in the percentage of T-helper type 1, T-helper 17, T-helper 17.1 and a decrease in T-helper type 2 compared to the population of healthy blood sample donors (p=0.001), except for patients from the 2 to 5 y/o age group. T-regulatory cells in absolute amount were reduced in all age groups (p<0.001), while their relative number corresponded to the norm in the 0 to 2 y/o age group (p=0.811) and decreased slightly in patients in older age groups, especially in the 2 to 5 y/o age group (p=0.030). Conclusion: the pathology of thymus development in patients with DDS leads to impaired maturation of T-lymphocytes, leading to an increase in the number of mature forms of T-lymphocytes, shifts towards the development of T-helper 1 and T-helper 17, and a decrease in T-regulatory cells. Disturbances in T-lymphocytes can cause changes (dysregulation) in subpopulations of B-cells. All these processes may underlie the progression of autoimmune and infectious complications in such patients that are increasing with aging.