Abstract
Defective adaptive immune responses are well studied in common variable immunodeficiency (CVID) patients; however, more focus is needed on innate immune system defects to explain CVID’s clinical and laboratory heterogeneity. This is the first study comparing migratory function of granulocytes, oxidative burst activity of phagocytic cells, surface integrin expressions on neutrophils and lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural killer T cells, lymphocyte subsets such as CD8+CD28+, CD4+CTLA-4+ cells in CVID patients (n: 20) and healthy controls (n: 26). The relationship between laboratory findings and some clinical was also investigated. CD3+CD8+ T cytotoxic cells were found to be elevated in CVID patients, but CD3+CD8+CD28+ or CD3+CD8+CD28− cells did not show any significant difference. CD4+CTLA-4+ cell percentages were significantly lower in CVID patients compared to healthy controls. Severe CVID patients had decreased percentages of NK cells with increased NK cell cytotoxicity suggesting possibly increased activation. Furthermore, CD3−CD16+CD56+CD28+ cells of CVID patients were elevated while percentage of CD28− NK cells was decreased. Neutrophil migration percentages were lower but and oxidative burst activity was not affected. CD11a expressions on these cells were depressed in contrast to increased expression of CD18. Innate immunity defects may affect the extent of recurrence and severity of infections in CVID. Our observations highlight some of these associations and indicate the need for further similar studies for improving better innate system evaluation batteries for these patients. Further phenotypic correlations of these analyses will help clinicians reach a more definitive target for the molecular genetic diagnostic of pediatric CVID patients.
Highlights
Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia, defective specific-antibody production, increased susceptibility to infections of the respiratory and gastrointestinal tracts with encapsulated bacteria and a variety of complications such as autoimmunity, lymphoproliferation, splenomegaly, malignancy, and granulomas [1]. defective adaptive immune responses with impairment of T cell and B cell maturation and activation are common features in most common variable immunodeficiency (CVID) patients, less attention has been given to innate immune system defects as a possible explanation for CVID heterogeneity [2].Innate immunity in CVIDNeutrophils and monocytes are essential to innate immunity
Functional and quantitative monocyte imbalances associated with T cell activation and with B cell disorders are observed in CVID [1]
Patients diagnosed as CVID but who did not fulfill these criteria were grouped as moderate disease (MD) group (n: 14)
Summary
Defective adaptive immune responses with impairment of T cell and B cell maturation and activation are common features in most CVID patients, less attention has been given to innate immune system defects as a possible explanation for CVID heterogeneity [2]. Neutrophils and monocytes are essential to innate immunity They are the first cells to migrate from the blood to the inflammatory site where they kill pathogens and secrete various mediators that regulate innate and adaptive immunity [3]. Monocytes can exhibit chronic hyperactivity and enhanced oxidative stress, which might contribute to autoimmune disorders, granuloma formation, and impaired natural killer (NK) cell-mediated cytotoxicity [1]. Functional steps required for the activity of neutrophils and monocytes include migration (detected by Migratest), recognition, adhesion, phagocytosis, and killing of the target (detected by Phagoburst test) [3]
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