ORIGINAL PAPER
B cells, autoimmunity, and innate immunity in 22q11.2 deletion syndrome: a two-center study and review of the literature
1
Department of Pediatric Immunology, Faculty of Medicine, Ege University, Izmir, Türkiye
2
Department of Pediatric Immunology, Dr Behcet Uz Children’s Education and Research Hospital, University of Health Sciences, Izmir, Türkiye
Submission date: 2025-02-23
Final revision date: 2025-07-16
Acceptance date: 2025-07-27
Online publication date: 2026-02-09
Corresponding author
Ezgi Topyildiz
Department of Pediatric Immunology, Faculty of Medicine, Ege University, Izmir, Türkiye
Department of Pediatric Immunology, Faculty of Medicine, Ege University, Izmir, Türkiye
KEYWORDS
ABSTRACT
Introduction:
A few studies have reported that 22q11.2 del syndrome (DiGeorge syndrome – DGS) is associated with alterations in B-lymphocytes and innate immunity that predispose to infections and autoimmunity. The present study investigated the B-cell compartment, autoimmunity markers, and components of innate immunity, including NK cells, NK-specific cytotoxicity, phagocytic functions, and adhesion molecules.
Material and Methods:
Thirty-five DGS patients and twenty healthy controls were evaluated. Nephelometric, flow cytometric, ELISA and immunofluorescence techniques were used.
Results:
There was no significant difference between the study and control groups regarding gender and age. Serum IgG, IgM levels and percentages, and antibodies against vaccine antigens were significantly lower in DGS patients. In DGS patients, 57.2% had low levels of non-switched memory B-cells, and 22.8% had low values of switched memory B-cells. Immature transitional B-cells, immature B-cells, plasmablasts, and active B-cells were significantly elevated. Autoantibodies were found positive in between 2.9% and 14.3% in the patient group. Natural killer T (NKT) cells and regulatory T cells (Tregs) were significantly decreased, whereas Fas+ active cytotoxic cells and Fas+ naive T helper cells were significantly elevated in DGS patients. NK-specific cytotoxicity was found to be higher in the patient group.
Conclusions:
Defects in humoral immunity, including immunoglobulin deficiencies and decreases in class-switched and nonclass-switched memory B-cell compartments, were common in DGS patients. While decreased Treg and NKT cells play a role in the increased incidence of autoimmunity, increased Fas+ cells counteract autoimmunity. Based on all these data, we would like to emphasize the importance of monitoring DGS patients for immune dysregulation.
A few studies have reported that 22q11.2 del syndrome (DiGeorge syndrome – DGS) is associated with alterations in B-lymphocytes and innate immunity that predispose to infections and autoimmunity. The present study investigated the B-cell compartment, autoimmunity markers, and components of innate immunity, including NK cells, NK-specific cytotoxicity, phagocytic functions, and adhesion molecules.
Material and Methods:
Thirty-five DGS patients and twenty healthy controls were evaluated. Nephelometric, flow cytometric, ELISA and immunofluorescence techniques were used.
Results:
There was no significant difference between the study and control groups regarding gender and age. Serum IgG, IgM levels and percentages, and antibodies against vaccine antigens were significantly lower in DGS patients. In DGS patients, 57.2% had low levels of non-switched memory B-cells, and 22.8% had low values of switched memory B-cells. Immature transitional B-cells, immature B-cells, plasmablasts, and active B-cells were significantly elevated. Autoantibodies were found positive in between 2.9% and 14.3% in the patient group. Natural killer T (NKT) cells and regulatory T cells (Tregs) were significantly decreased, whereas Fas+ active cytotoxic cells and Fas+ naive T helper cells were significantly elevated in DGS patients. NK-specific cytotoxicity was found to be higher in the patient group.
Conclusions:
Defects in humoral immunity, including immunoglobulin deficiencies and decreases in class-switched and nonclass-switched memory B-cell compartments, were common in DGS patients. While decreased Treg and NKT cells play a role in the increased incidence of autoimmunity, increased Fas+ cells counteract autoimmunity. Based on all these data, we would like to emphasize the importance of monitoring DGS patients for immune dysregulation.
REFERENCES (24)
1.
Grinde D, Overland T, Lima K, et al. (2020): Complement activation in 22q11.2 deletion syndrome. J Clin Immunol 40: 515-523.
2.
Deshpande DR, Demirdag YY, Marsh RA, et al.; The USIDNET Consortium (2021): Relationship between severity of T-cell lymphopenia and immune dysregulation in patients with DiGeorge syndrome (22q11.2 deletions and/or related TBX1 mutations): a USIDNET study. J Clin Immunol 41: 29-37.
3.
Yu HH, Chien YH, Lu MY, et al. (2022): Clinical and immunological defects and outcomes in patients with chromosome 22q11.2 deletion syndrome. J Clin Immunol 42: 1721-1729.
4.
Zheng P, Noroski LM, Hanson I, et al. (2015): Molecular mechanisms of functional natural killer deficiency in patients with partial DiGeorge syndrome. J Allergy Clin Immunol 135: 1293-1301.
5.
Aresvik DM, Overland T, Lima K, et al. (2019): Lymphocyte apoptosis and FAS expression in patients with 22q11.2 deletion syndrome. J Clin Immunol 39: 65-74.
6.
Mustillo PJ, Sullivan KE, Chinn IK, et al. (2023): Clinical practice Guidelines for the immunological management of chromosome 22q11.2 deletion syndrome and other defects in thymic development. J Clin Immunol 2023; 43: 247-270.
7.
Aksu G, Genel F, Koturoglu G, et al. (2006): Original serum immunoglobulin (IgG, IgA and IgM) and IgG subclass concentrations in healthy children: A study using nephelometric technique. Turk J Pediatr 48: 19-24.
8.
Kutukculer N, Azarsız E, Aksu G, Karaca NE (2016): CD4+CD25+Foxp3+ T regulatory cell, Th1 (CCR5, IL-2, IFN-gamma) and Th2 (CCR4, IL-4, IL-13) type chemokines in children with common variable immunodeficiency. Int J Immunopathol Pharmacol 29: 241-251.
9.
Gupta S, Aggarwal S, Nguyen T (1998): Increased spontaneous apoptosis in T lymphocytes in Di George anomaly. Clin Exp Immunol 113: 65-71.
10.
Böhler T, Wintergerst U, Linde R, et al. (2001): CD95 (Apo-1/Fas) expression on naive CD4+ T-cells increases with disease progression in HIV-infected children and adolescents: effect of highly active antiretroviral therapy. Pediatr Res 49: 101-108.
11.
Kutukculer N, Azarsız E, Karaca NE, et al. (2015): A clinical and laboratory approach to the evaluation of innate immunity in pediatric CVID patients. Front Immunol 6: 1-10.
12.
Ozen S, Akcal O, Taskirdi İ, et al. (2021): 22q11.2 deletion syndrome: 20 years of experience from two pediatric immunology units and review of clues for diagnosis and disease management. Allergol Immunopathol (Madr) 49: 95-100.
13.
McLean-Tooke A, Barge D, Spickett GP, Gennery AR (2008): Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol 122: 362-367.
14.
Patel K, Akhter J, Kobrynski L, et al. (2012): Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge syndrome. J Pediatrics 161: 950-954.
15.
Finocchi A, Di Cesare S, Romiti ML, et al. (2006): Humoral immune responses and CD27+ B-cells in children with DiGeorge syndrome (22q11.2 deletion syndrome). Pediatr Allergy Immunol 17: 382-388.
16.
Van Kaer L, Wu L (2018): Therapeutic potential of invariant natural killer cells in autoimmunity. Front Immunol 9: 519-526.
17.
Vila J, Isaacs JD, Anderson AE (2009): Regulatory T-cells and autoimmunity. Curr Opin Hematol 16: 274-279.
18.
Georgiev P, Charbonnier LM, Chatila T (2019): Regulatory T-cells: The many faces of foxp3. J Clin Immunol 39: 623-640.
19.
Ueda H, Howson JMM, Esposito L, et al. (2003): Association of the T-cell regulatory gene CTLA-4 with susceptibility to autoimmune disease. Nature 423: 506-511.
20.
Navratil JS, Liu CC, Ahearn JM (2006): Apoptosis and autoimmunity. Immunol Res 36: 3-12.
21.
Gupta S, Aggarwal S, Nguyen T (1998): Increased spontan apoptosis in T lymphocytes in Digeorge anomaly. Clin Exp Immunol 113: 65-71.
22.
Sirianni MC, Businco L, Seminara R, Aluti F (1983): Severe combined immunodeficiencies, primary T-cell defects and DiGeorge syndrome in humans; characterization by monoclonal antibodies and natural killer cell activity. Clin Immunol Immunopathol 28: 361-370.
23.
Hartenstein V, Martinez P (2019): Phagocytosis in cellular defense and nutrition: a food-centered approach to the evolution of macrophages. Cell Tissue Res 377: 527-547.
24.
Fan ST, Brian AA, Lollo BA, et al. (1993): CD11a/CD18 (LFA-1) integrin engagement enhances biosynthesis of early cytokines by activated T-cells. Cell Immunol 148: 48-59.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
