Antibody levels following vaccination against SARS-CoV-2 during an 11-month follow-up.

AIMS: The primary aim of our monitoring was to determine the duration of persistence of antibody levels following administration of the Comirnaty (Pfizer/BioNTech) mRNA vaccine. The second aim was to analyse the effect of selected factors on the level of antibodies. METHODS: The study cohort consisted of 250 employees of the Medirex JSC laboratories. For the quantitative determination of specific IgG anti-S1 and anti-S2 antibodies to SARS-CoV-2, chemiluminescence immunoassay was used. Twenty-nine subjects were excluded from the analysis due to extreme values of antibody levels in individual measurements. The effect of gender, age, BMI, comorbidity, and adverse reactions after vaccination with the Comirnaty (Pfizer/BioNTech) mRNA vaccine on antibody levels was analysed. Comparisons were made for five samples collected from two weeks after the 1st dose to 36 weeks after the 2nd dose of the mRNA vaccine. After the fifth sampling, the cohort was divided into two groups. Group 1 received the 3rd dose, and Group 2 were controls. We performed the last (sixth) sample collection two weeks after booster administration in Group 1and 11 months after the 2nd dose of the vaccine in controls. Between months 8 and 10 after the 2nd dose, we performed a cellular immunity test. RESULTS: Altogether 99.6% of the participants had a positive antibody level at week 36. Antibodies were still present in controls at month 11 after the 2nd dose. Significantly higher antibody levels were found in females, younger subjects, and those with selected adverse reactions. Reactive specific T lymphocytes were present in 65.6% of the subjects between weeks 36 and 44. CONSLUSION: The antibody response decreased with the time since the 2nd dose but was still present in the control group at week 48. The effect of booster on antibody levels was clearly demonstrated. We have not confirmed an association of cellular immunity with the level of antibodies or with the antibodies present.

TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients.

OBJECTIVE: In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14+ blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. RESULTS: Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR = 1.001, P = 0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14+ TREM-1+ cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14+ TREM-2+ monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14+ TREM-1+ cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2+ CD14+ monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14+ TREM-2+ cells. CONCLUSION: We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient's overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.

TREM-1 and TREM-2 Expression on CD14+ Cells in Bronchoalveolar Lavage Fluid in Pulmonary Sarcoidosis and Hypersensitivity Pneumonitis in the Context of T Cell Immune Response.

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are immunologically mediated processes caused by hypersensitivity reaction accompanied by similar features including lymphocytic alveolitis and granuloma formation. Recent studies describe the role of TREM receptors in T cell activation, differentiation, and granuloma formation. Alveolar macrophages activation via TREM receptors may be the key factor mediating subsequent immune response. The aim of the study was to analyse TREM-1 and TREM-2 expression to identify further molecular mechanisms participating in the immunopathogenesis of sarcoidosis and HP. METHODS: Flow cytometry was performed to analyse TREM-1 and TREM-2 expression on CD14+ cells in bronchoalveolar lavage fluid from patients having sarcoidosis or HP and a control group. RESULTS: The study proved increased TREM-1 expression on alveolar macrophages in pulmonary sarcoidosis and diminished TREM-1 expression in HP-Sarcoidosis: median: 76.7; HP: median: 29.9; control: median: 53.3, (sarcoidosis versus HP: p < 0.001; sarcoidosis versus control: p < 0.05). TREM-2 expression was increased in both, sarcoidosis and HP-sarcoidosis: median: 34.79; HP: median: 36.00; control: median: 12.98, (sarcoidosis versus control: p < 0.05; HP versus control: p < 0.05). Correlation analysis showed negative correlation between TREM-1 and total number of CD8+ cytotoxic T cells. In sarcoidosis TREM-1 expression decreased with changes of HRCT image, decrease in CD4/CD8 ratio and decrease in DLCO. CONCLUSIONS: Differences in TREM receptor expression in sarcoidosis (increase in TREM-1 and TREM-2) and HP (increase in TREM-2) and correlation analysis suggests that activation via TREM may participate in typical immunological characteristics of sarcoidosis and HP.

Vitamin D deficiency - a potential risk factor for sepsis development, correlation with inflammatory markers, SOFA score and higher early mortality risk in sepsis.

OBJECTIVES: Sepsis is a life-threatening organ dysfunction generated due to the dysregulation of the immune response to infection. The aim of this study was to highlight the role of vitamin D in sepsis and non-infectious SIRS (systemic inflammatory response syndrome) and to find correlation of vitamin D levels with inflammatory markers, severity of the disease, and association with the 7th and 28th survival rate of patients. METHODS: We investigated 32 patients (21 men, 11 women) admitted to an intensive care unit with both SIRS and sepsis. Blood was taken within 24 hours after admission. Plasma levels of 25(OH)D, sTREM-1, CRP, presepsin and procalcitonin were investigated. RESULTS: Patients with sepsis had lower levels of 25(OH)D (n = 25) than SIRS patients (n = 7; p = 0.0032). Significantly lower levels of 25(OH)D were found also in patients, who did not survive the 7th  (p = 0.0076) and 28th day  (p = 0.0338) of hospital care compared to 7th, resp. 28th day survivors. We revealed a negative correlation between the levels of 25(OH)D and inflammatory markers CRP (p = 0.0003), presepsin (p = 0.0032) and sTREM-1 (p = 0.0065) in all SIRS/sepsis patients and clinical condition (SOFA score; p = 0.0385). CONCLUSION: Our results showed that vitamin D deficiency predisposed to the development of sepsis, negatively correlated with CRP, presepsin, sTREM-1 and SOFA score and their levels associates with both 7th and 28th days survival of patients (Tab. 5, Ref. 64).

Increased antifungal antibodies in bronchoalveolar lavage fluid and serum in pulmonary sarcoidosis.

The recent studies suggest a role of fungi in development of sarcoidosis. Moreover, the immune response in sarcoidosis and fungal infection shows a striking similarity. We formulated a hypothesis of the possible increase in antifungal antibodies in bronchoalveolar lavage fluid (BALF) and serum in pulmonary sarcoidosis. BALF and serum levels of IgG-, IgM- and IgA-specific antibodies against the cell wall ß-D-glucan and mannan of Candida albicans and Saccharomyces cerevisiae were tested in 47 patients (29 pulmonary sarcoidosis patients and 18 patients with other interstitial lung diseases (ILD - control group)) and 170 healthy controls. Our results proved: (1) an increase in IgG-, IgM- and IgA-specific antifungal antibodies in BALF in pulmonary sarcoidosis compared with the control group (C. albicans: IgG: P = 0.0329, IgM: P = 0.0076, IgA: P = 0.0156; S. cerevisiae: IgG: P = 0.0062, IgM: P = 0.0367, IgA: P = 0.0095) and (2) elevated levels of serum antifungal antibodies in pulmonary sarcoidosis compared with healthy controls (C. albicans: IgG: P = 0.0329, IgM: P = 0.0076, IgA: P = 0.0156; S. cerevisiae: IgG: P > 0.05, IgM: P < 0.05, IgA: P < 0.001). The study showed increased serum and BALF levels of antifungal antibodies in pulmonary sarcoidosis. The hypothesis that fungal infection is one of the possible aetiologic agents of sarcoidosis is interesting and deserves further attention.

Diagnostic value of TREM-1 and TREM-2 expression in bronchoalveolar lavage fluid in sarcoidosis and other lung diseases.

BACKGROUND: Triggering receptors expressed on myelocytes (TREM) belong to new molecules with a great role in innate immune system and inflammation. While TREM-1 is known for its pro-inflammatory activity, the TREM-2 has anti-inflammatory activity and has a great impact on granuloma formation, typical sign of sarcoidosis and other granulomatous diseases. METHODS: In our study, we compared the TREM-1 and TREM-2 receptor expressions on the myeloid cell surfaces in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis (PS), other interstitial lung diseases (ILD), asthma bronchiale (AB), pneumonia, lung cancers, and Quantiferon TB positive patients. RESULTS: We found increased number of all TREM variables (total number, percentage, and mean fluorescence intensity /MFI/) of TREM-1 and TREM-2 positive cells in PS and AB patients compared to the control group of patients with other ILD. In patients with pneumonia, only expression of TREM-1 receptor was increased. In ILD, AB and group of pneumonia patients, the increase of TREM-1 and TREM-2 expression was associated with an increased number of eosinophils. CONCLUSION: TREM-1 and TREM-2 tests are good diagnostic tests for sarcoidosis. Their sensitivity and specificity are comparable with the currently common using test, that of CD4/CD8 ratio. The combination of both tests (CD4/CD8 ratio test together with TREM-1 and TREM-2 tests) resulted in an increased sensitivity and specificity (Tab. 7, Fig. 1, Ref. 28).

Main targets of tetraaza macrocyclic copper complex on L1210 murine leukemia cells.

Several metal complex agents have already been introduced into clinical tumor therapy and others are subject of antitumor studies. In this study we focused on the tetraaza macrocyclic copper complex (Cu(TAAB)Cl(2)). We studied the influence of the substance on cell growth, cell cycle, membrane integrity, necrosis, apotosis and glutathione level on the leukemic cell line L1210 in 1-day (22 h) and 3-day (72 h) experiments. The metal complex shows a dose-dependent antiproliferative effect, without affecting cell cycle phases. The present results confirm that copper complex can damage plasmatic membranes and trigger apoptosis, and that after treatment of leukemic cells with the copper complex, glutathione levels were increased.

Alterations in lymphocyte subpopulations in peripheral blood at manifestation of type 1 diabetes mellitus in childhood.

BACKGROUND: Alterations in cellular immunity at manifestation of type 1 diabetes mellitus, as described in publications so far, are equivocal. Moreover, the age of children was usually not taken into account. OBJECTIVES: Exact inferentially statistical measures were used to arrive at reliable information. METHODS: Thirty four diabetic children and 48 normals were taken randomly according to the established criteria, and scrutinized. Lymphocyte subpopulations counts were measured by flow cytometry using three-color-labelled monoclonal antibodies against cell surface markers. The resulting absolute cell counts as well as percentages from the total lymphocyte count were expressed in terms of univariate and bivariate 95% confidence intervals. They render an illustrative way for defining statistically significant (alpha = 5%) differences between health and disease. RESULTS: The CD8, CD16 absolute counts in younger diabetics were significantly decreased in average to 96-58% of the normal subgroup. For older children, CD4, CD8, CD16 and CD19 absolute counts were significantly lowered to 75-61% of the norm. Relative changes in Ly subpopulations were less pronounced. The immunoregulatory index increased significantly to 125-128% of the norm in either age group. The proportion of CD4 memory cells from the total of naive and memory cells was significantly increased to 122-133% of the norm in diabetic children of either age group. CONCLUSION: More significant changes of lymphocyte subpopulations than those given in literature were revealed at manifestation of childhood type 1 diabetes. They testify to the autoimmune pathogenesis of the type 1 diabetes mellitus. (Tab. 3, Fig. 4, Ref. 18.)