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Simple Summary: This article addresses the topic of primary immunodeficiencies, with particular emphasis on antibody deficiencies with near-normal immunoglobulin levels or hyperimmunoglobulinemia. This paper goes beyond genetics and emphasizes the importance of the immune system and particularly immune checkpoints and Epstein–Barr virus (EBV) reactivation in the context of these disorders. The article delves into the immune dysregulations occurring in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical picture of patients and, in the future, may contribute to the development of cancer, especially those related to hematological malignancies. Disturbances observed in the immunopathogenesis of the presented diseases go beyond the accepted scheme, with the development of PID largely associated only with genetic disorders, and the article emphasizes that the regulation of immunity and virus reactivation also contributes to the progression of PID. This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein–Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a group of metabolic disorders with different etiologies, pathogeneses and clinical pictures, characterized by chronic hyperglycemia due to abnormal insulin secretion or action. Type 1 diabetes mellitus is the most common type of diabetes mellitus in children and adolescents, accounting for about 90% of diabetes in the population under the age of 18. The etiopathogenesis of type 1 diabetes is multifactorial. The disease occurs as a result of the interaction of three factors: genetic predisposition, environmental factors and the immune response. Research in recent years has focused on the involvement of Epstein–Barr virus (EBV) in the pathogenesis of type I diabetes. The goals of treating type 1 diabetes include maintaining blood-glucose, fructosamine and glycated hemoglobin (HbA1c) levels; therefore, the main purpose of this study was to evaluate the effect of EBV infection on the activation of selected immune cells, fructosamine levels and HbA1c levels in children with type I diabetes. Based on our study, we found a lower percentage of CD8+ T lymphocytes with expression of the CD69 molecule in patients with anti-VCA antibodies in the IgG class, and a lower percentage of CD8+ T lymphocytes with expression of the CD25+ molecule in patients with anti-EBNA-1 antibodies in the IgG class, which may indicate limited control of the immune system during EBV infection in patients. There was a lower percentage of CD3+CD4+ T lymphocytes secreting IL-4 in the study group, indicating that a deficiency in IL-4 production may be related to the development of type 1 diabetes. There was an increase in the percentage of CD4+CD3+IL-10 lymphocytes in the study group with anti-VCA antibodies present in the IgG class and anti-EBNA-1 antibodies in the IgG class compared to the patients without antibodies. In addition, there was a significant increase in fructosamine levels and higher glycated hemoglobin levels in the study group with antibodies to EBV antigens. In addition, an increase in the percentage of T lymphocytes with a CD4+CD3+IL-17+ phenotype in the patients with anti-VCA IgG antibodies was confirmed, and higher HbA1c levels may suggest that EBV infection is accompanied by an increase in IL-17 secretion. [ABSTRACT FROM AUTHOR]