Regulatory T and B cells in transient hypogammaglobulinemia of infancy.

BACKGROUND: Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder caused by an abnormal delay in reaching normal IgG levels in the first three years of life. Although THI is a common primary immune deficiency, its pathogenesis has not been fully elucidated. We aimed to investigate the role of regulatory T cells (Tregs) and B cells (Bregs) in the pathogenesis of THI. METHODS: T and B cell subsets were evaluated in 40 patients with THI aged 6-41 months and 23 healthy controls aged 6-51 months using flow cytometry. CD4 and interleukin-2 receptor-α alpha (CD25) expression and a lack of interleukin-7 receptor-α (CD127) were used for Treg identification. FoxP3 expression in Tregs was determined as a percentage and mean fluorescence intensity. B cell subsets (plasmablast, mature naive, primarily memory, new memory) and Bregs were defined according to CD19, CD38, and CD24 expressions. RESULTS: Patients with THI (15 females and 25 males; mean age: 18.8 ± 8.6 months) and controls (10 females and 13 males; mean age: 22.6 ± 13.1 months) participated in this study. While the proportion of Tregs of children with THI were significantly increased compared to the controls, primarily memory B cells were reduced. Additionally, the proportions of CD127 in CD3+ and CD3+CD4+ T cells were significantly reduced in the patients with THI compared to the control. No significant difference was detected in the FoxP3 expression of Tregs and the frequency of Bregs in the children with THI. CONCLUSIONS: Increased Tregs and decreased primarily memory B cells may cause antibody production delay in children with THI. Changes in the T and B cell compartments may be related to chronic immune activation and affected cellular immunity in THI. Further studies are needed to use T and B cell subsets in the prediction of IgG level recovery.

Reduced Monocyte Subsets, Their HLA-DR Expressions, and Relations to Acute Phase Reactants in Severe COVID-19 Cases.

Monocytes are one of the principal immune defense cells that encounter infectious agents. However, an essential role of monocytes has been shown in the spread of viruses throughout the human body. Considering this dilemma, this study aimed to evaluate monocyte subsets and Human Leukocyte Antigen-DR isotype (HLA-DR) expressions in clinical coronavirus disease 2019 (COVID-19) cases. This prospective, multicenter, case-control study was conducted with COVID-19 patients and healthy controls. The patient group was divided into two subgroups according to disease severity (severe and non-severe). Three monocyte subsets (classical, CL; intermediate, INT; non-classical, NC) were analyzed with flow cytometry upon the patients' hospital admission. A total of 42 patients with COVID-19 and 30 controls participated in this study. The patients' conditions were either severe (n = 23) or non-severe (n = 19). All patients' monocyte and HLA-DR expressions were decreased compared with the controls (p < 0.05). Per disease severity, all monocyte subsets were not significant with disease severity; however, the HLA-DR expressions of CL monocytes (p = 0.002) and INT monocytes (p = 0.025) were more decreased in the severe patient group. In patients with various clinical features, NC monocytes were more affected. Based on these results, NC monocytes were more decreased in acute COVID-19 cases, though related various clinics decreased all monocyte subsets in these patients. Decreased monocyte HLA expressions may be a sign of immune suppression in severe patients, even when the percentage of monocyte levels has not decreased yet.

The Role of Regulatory T and B Cells in the Etiopathogenesis of Idiopathic Granulomatous Mastitis.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the role of T- and B-regulatory cells (Tregs and Bregs) in the pathogenesis of idiopathic granulomatous mastitis (IGM). METHODS: This study includes 47 patients with pathologically proven IGM (Group P) and 26 healthy subjects (Group C). The patients in Group P were divided into two groups according to whether their lesions were active (Group PA, n: 21) or in remission (Group PR, n: 26). By using flow-cytometry, the frequencies of CD3+CD4+CD45RA-Foxp3high activated Tregs (aTregs), CD3+CD4+CD45RA-Foxp3low non-suppressive Tregs, CD3+CD4+CD45RA+Foxp3low resting Tregs (rTregs), CD3+CD4+CD25+Foxp3- T-effector cells (Teff), total Tregs and Bregs were analyzed in all subjects. RESULTS: The frequency of the Teff cells was statistically higher in Group P when compared with Group C (p =.004). The Foxp3 expression of Treg cells and the frequency of non-suppressive Tregs in Group P were statistically lower than Group C (p =.032 and p =.02, respectively). In addition, Group PR's Foxp3 expressions were statistically lower than Group C (p =.027); Group PR's aTregs ratio was statistically lower than Group PA (p =.021); and the non-suppressive Tregs ratio of Group PR was lower than both Group PA and Group C (p =.006 and p <.0001). No significant differences were seen Bregs and B cell subsets. CONCLUSION: Significant changes in Foxp3 expression and Treg subsets were seen in patients with active IGM lesion and in remission. This study shows an intrinsic defect of Tregs in patients with IGM.

Correlation of myeloid-derived suppressor cells with C-reactive protein, ferritin and lactate dehydrogenase levels in patients with severe COVID-19.

The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings-aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets-polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs-by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.

The alteration of lymphocyte subsets in idiopathic granulomatous mastitis

Background and aim: This study analyzed peripheral blood lymphocyte subsets to determine their role in the etiopathogenesis of IGM. Materials and methods: This study includes 51 pathologically proven IGM patients (active disease: 26 and in remission: 25) and 28 healthy volunteers. The analyses of lymphocyte subsets were performed by flow cytometric immunophenotyping. Results: The percentage of T helper lymphocyte of all IGM patients were lower than control groups (p = 0.001). Absolute cytotoxic T lymphocyte count (p = 0.03), both percentage (p = 0.035) and absolute count (p = 0.002) of the natural killer cells, and both percentage (p = 0.038) and absolute count (p = 0.008) of natural killer T cells, were higher than the control group. The T helper lymphocyte percentage of the patients with active disease was lower than the control group (p = 0.0003). The absolute cytotoxic T lymphocyte (p = 0.029) and natural killer T cells (p = 0.012) of the patients with active disease were higher than the control group. Conclusion: Idiopathic granulomatous mastitis is defined as a localized form of granulomatous disorders. However, the observed changes in T cells, NK, and NKT cells suggest that there is systemic immune dysregulation in patients with IGM.

Response to trastuzumab and investigation of expression profiles of matrix metalloproteinase-related proteins in primary breast cancer stem cells.

Breast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2+ BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2+ BCSCs (CD44+CD24-HER2+), HER2- BCSCs (CD44+CD24-HER2-), HER2- primary culture cells (CD44+CD24+HER2-) and triple positive primary culture cells (CD44+CD24+HER2+). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2+ BCSCs than in primary culture. HER2- BCSCs were more resistant to drugs than HER2+ BCSCs. Our findings suggest that the presence of HER2- BCSCs may be responsible for primary trastuzumab resistance in HER2+ BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs.

Apoptosis-induced T-cell lymphopenia is related to COVID-19 severity.

Increased levels of acute-phase reactants and lymphopenia are predictors of disease severity in coronavirus disease 2019 (COVID-19). This study aimed to investigate the role of apoptosis in the etiology of lymphopenia in patients with COVID-19. This multicentered, prospective, and case-control study was conducted with polymerase chain reaction (+) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and an age-gender-matched control group. Samples were taken at the time of diagnosis and analyzed via flow cytometry within 24 h. The participants' demographic data and initial laboratory tests were also recorded. In total, 33 patients with COVID-19 (mean age = 45.4 ± 17.2) and 25 controls (mean age = 43.4 ± 17.4) participated in the study. All patients were identified as having mild (16), moderate (5), or severe (12) disease severity. Both early and late apoptotic cells in B and T lymphocytes were increased in all patients with COVID-19 (p < .05). Early apoptotic (EA) B and T lymphocytes were also higher in severe cases compared to mild cases (p = .026). There was no significant difference between lymphopenia and apoptosis in patients with COVID-19. However, patients with lymphopenia (n = 14) and severe COVID-19 (p = .013) had increased EA T lymphocytes. This study's results show that B and T lymphocytes' apoptosis increases in patients with COVID-19. In addition, enhanced T lymphocyte apoptosis is associated with disease severity in lymphopenic patients with COVID-19.

Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children

Background/aim: The serum immunoglobulin levels are used routinely in clinical practice because they provide key information on the humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthy children. Materials and methods: A total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serum immunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals, and IgG subclasses in 6 groups of children aged more than 2 years. Results: The serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximum level at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While the lowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclasses varied depending on the age groups. Conclusion: The updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immune deficiencies.

The effect of zinc and melatonin supplementation on immunity parameters in breast cancer induced by DMBA in rats.

OBJECTIVE: The aim of the study was to determine the effects of zinc and melatonin supplements on the immunity parameters of female rats with breast cancer induced by DMBA. METHODS: Group 1; Control, Group 2; 7,12-dimethylbenz[a]anthracene (DMBA), Group 3; DMBA + zinc, Group 4; DMBA + melatonin, Group 5; DMBA + zinc + melatonin. The rats' breast cancer was induced by DMBA 80 mg/kg. Groups 3-5 received daily 5 mg/kg doses of zinc, melatonin, and zinc + melatonin, respectively. Lymphocyte rates, T-lymphocyte subgroups, B-lymphocyte and natural killer cells (NK), and natural killer T (NKT) were evaluated. RESULTS: The most significant increase in lymphocyte, T-lymphocyte, and CD4 lymphocyte rates was found in Group 5. The highest NKT cell rates were found in Group 3. CONCLUSIONS: Findings show that zinc and melatonin supplements have led to an increase in the immunity parameters of rats with breast cancer.