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Marina Delić-Šarac

Društvene mreže:

S. Meyer, I. Blaas, Ravi Chand Bollineni, Marina Delić-Šarac, T. Tran, C. Knetter, Ke-Zheng Dai, T. Madssen, J. Vaage et al.

Jon Riise, S. Meyer, I. Blaas, A. Chopra, T. Tran, Marina Delić-Šarac, Malu Lian Hestdalen, E. Brodin, E. Rustad et al.

B‐cell depletion induced by anti‐cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccination, but effects on CD8 T‐cell responses are unknown. Here, we investigated humoral and CD8 T‐cell responses following two vaccinations in patients with lymphoma undergoing anti‐CD20‐mAb therapy as single agent or in combination with chemotherapy or other anti‐neoplastic agents during the last 9 months prior to inclusion, and in healthy age‐matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor‐binding domain of the SARS‐CoV‐2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T‐cell responses against prevalent human leucocyte antigen (HLA) class I SARS‐CoV‐2 epitopes were determined by peptide‐HLA multimer analysis. Strong CD8 T‐cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS‐CoV‐2‐vaccinated, anti‐CD20‐treated patients with lymphoma, their CD8 T‐cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B‐cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID‐19) vaccines, and development of vaccines aimed at eliciting T‐cell responses to non‐Spike epitopes might provide improved protection.

S. Meyer, I. Blaas, R. C. Bollineni, Marina Delić-Šarac, T. Tran, C. Knetter, Ke-Zheng Dai, Torfinn Støve Madssen, J. Vaage et al.

T-cell epitopes with broad population coverage may form the basis for a new generation of SARS-CoV-2 vaccines. However, published studies on immunoprevalence are limited by small test cohorts, low frequencies of antigen-specific cells and lack of data correlating eluted HLA ligands with T-cell responsiveness. As the protective role of pre-existing cross-reactivity to homologous peptides is unclear, we aimed to identify SARS-CoV-2-specific minimal epitopes recognized by CD8 T-cells among 48 peptides eluted from prevalent HLA alleles, and an additional 84 predicted binders, in a large cohort of convalescents (n=83) and pre-pandemic control samples (n=19). We identified nine conserved SARS-CoV-2-specific epitopes restricted by four of the most prevalent HLA class I alleles in the Norwegian study cohort, to which responding CD8 T cells were detected in 70-100% of convalescents expressing the relevant HLA allele. Only two of these were derived from the Spike protein, included in current vaccines. We found a strong correlation between immunoprevalence and immunodominance. Thus, the CD8 T-cell response to SARS-CoV-2 is more focused than previously believed. Using a new algorithm, we predict that a vaccine including these epitopes could induce a T-cell response in 83% of Caucasians.

S. Meyer, I. Blaas, R. C. Bollineni, Marina Delić-Šarac, T. Tran, C. Knetter, Ke-Zheng Dai, T. Madssen, J. Vaage et al.

T-cell epitopes with broad population coverage may form the basis for a new generation of SARS-CoV-2 vaccines. However, published studies on immunoprevalence are limited by small test cohorts, low frequencies of antigen-specific cells and lack of data correlating eluted HLA ligands with T-cell responsiveness. As the protective role of pre-existing cross-reactivity to homologous peptides is unclear, we aimed to identify SARS-CoV-2-specific minimal epitopes recognized by CD8 T-cells among 48 peptides eluted from prevalent HLA alleles, and an additional 84 predicted binders, in a large cohort of convalescents (n=83) and pre-pandemic control samples (n=19). We identified nine conserved SARS-CoV-2-specific epitopes restricted by four of the most prevalent HLA class I alleles in the Norwegian study cohort, to which responding CD8 T cells were detected in 70-100% of convalescents expressing the relevant HLA allele. Only two of these were derived from the Spike protein, included in current vaccines. We found a strong correlation between immunoprevalence and immunodominance. Thus, the CD8 T-cell response to SARS-CoV-2 is more focused than previously believed. Using a new algorithm, we predict that a vaccine including these epitopes could induce a T-cell response in 83% of Caucasians.

Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome.

Introduction: Anti GAD (antibodies on glutamic acid decarboxylase) and anti-IA2 antibodies (against tyrosine phosphatase), today, have their place and importance in diagnosis and prognosis of Type 1 diabetes. Huge number of patients with diabetes mellitus type 1 have these antibodies. Insulin antibodies are of critical importance in diagnosis of diabetes mellitus type 1 for pediatric population. Materials and methods: During 2014, the samples of 80 patients from Clinical Center University Sarajevo (CCUS) Pediatrics clinic’s, Endocrinology department were analyzed on anti-GAD and IA2 antibodies. The samples of serums of all patients were analyzed with ELISA tests using Anti GAD ELISA (IgG) kites from EUROIMMUN company. These are quantitative in vitro tests for human antibodies against decarboxylase of glutamine acid (GAD) and IA2, in serum or EDTA plasm. Results: During the period of one year, in CCUS’s Organizational unit, Institute for Clinical Immunology, 80 samples of patients with anti GAD and IA2 antibodies were analyzed. Out of total number of samples, 41 were male patients, or 51% and 39 female, or 49%. The youngest patient was born in 2012, and the oldest in 1993. Age average was represented by the patients born in 2001. Share of positive results for IA2 antibodies and GAD antibodies was 37% for IA2 antibodies, and 63% for GAD antibodies. Discussion: During an autoimmune – mediated Diabetes mellitus type 1 leads to T-cell mediated destruction of beta cells of pancreatic islets, reduced production of insulin and glucose metabolism. Studies have shown that these bodies are the most intense single marker for identifying persons with increased risk for diabetes development.

Aim: The main aim of this research was to determine the influence of socioeconomic status and residence/living conditions on the status of oral health (e.g. health of mouth and teeth) in primary school students residing in Canton Central Bosnia. Methods: The study was designed as a cross-sectional study. Our research included two-phased stratified random sample of 804 participants. The quantitative research method and newly designed survey instrument were utilized in order to provide data on the oral health of the examined children. The alternate hypothesis foresaw that “there were significant statistical differences between the levels of incidence of dental caries in comparison to the incidence in children of different socioeconomic status. Results: The Chi square () of 22.814, degree of freedom (Df) = 8, coefficient of contingency of 0.163 and T-test (Stat) of–0.18334 showed that there were no significant statistical differences at p < 0.05 level between the primary school children from urban and rural areas. The obtained results showed that the caries indexes in elementary schools in Central Bosnia Canton were fairly uniform. Research showed that there were a difference in the attitudes towards a regular dental visits, which correlated with social-educational structure of the children's’ families. Conclusion: According to the results, we can see that the socioeconomic status of patients had an effect on the occurrence of dental caries and oral hygiene in patients in relation to the rural and urban areas, because we can see that by the number of respondents, the greater unemployment of parents in both, rural and urban areas, caused a host of other factors, which were, either, directly or indirectly connected with the development of caries.

AIM To investigate an influence of the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) in serum on the activity of inflammatory bowel disease (IBD). METHODS The IBD patients of both genders (n=60) were divided in two equal groups, ulcerative colitis (UC) and Crohn's disease (CD). Based on the result of activity index each group was subdivided in two subgroups: active and inactive phase of the disease. Age and gender matched apparently healthy individuals (n=30) involved in the control group. Serum TNF-α concentration was determined by enzyme linked immune-adsorbent assay (ELISA). RESULTS The significant difference (Mann-Whitney Test) in serum TNF-α level was found between healthy controls 28.86 pg/ml (28.74 - 29.19 pg/ml) and CD patients (29.47 pg/ml (29.1 - 29.77 pg/ml) (p less than 0.05) and UC patients 29.34 pg/ml (29.14 - 29.71 pg/ ml) (p less than 0.05) respectively. Serum TNF-α level in patients with CD was higher compared to serum TNF-α level in patients with UC, but the difference was not significant (p more than 0,05). There were no significant difference in serum TNF-α concentrations either in CD or UC patients related to the phase of disease activity: active CD 29.53 pg/ml (29.20 - 29.90 pg/ml) vs inactive CD 29.26 pg/ml (29.15 - 29.53 pg/ml); active UC 29.53 pg/ml (29.32 - 29.85 pg/ ml) vs inactive UC 29.26 pg/ml (29.10 - 29.63 pg/ml). CONCLUSIONS Since there were no differences in serum TNF-α concentrations related to the disease activity we consider that TNF-α is not an adequate serum biomarker for an assessment of the disease activity in patients with IBD.

INTRODUCTION This study represents a new approach to the extended analysis of correlation of findings of oligoclonal bands on gels and the level of intrathecal synthesis of immunoglobulin G in the central nervous system. Previous studies have shown that there is no correlation at this level as well as the number of tape or finding does not correlate with the forecast effect of therapy or patient outcome. AIMS OF THE STUDY To determine the correlation of level of immunoglobulins IgG in CSF with the number of oligoclonal bands on the gel. MATERIAL AND METHODS The retrospective study based on data processed in Clinical Immunology Clinical Center University of Sarajevo. Patients were assumed of multiple sclerosis according to clinical findings and magnetic resonance imaging. All CSF and serum samples were processed by nephelometry, isoelectric focusing on the gel. Statistical analysis of results was also performed by using SPSS statistical analysis program. RESULTS Analyses were performed on 254 samples of cerebrospinal fluid and serum of patients from neurological clinic, suspected of multiple sclerosis. We concluded that there is no correlation between the level of intrathecal synthesis obtained by Reibergram with the number of oligoclonal bands on gels. We think that the reason could be a small sample of patients analyzed and it leaves room for future analysis on a larger sample. DISCUSSION AND CONCLUSION For most patients with established MS we found intrathecal humoral response, type two, and the number and arrangement of IgG bands generally does not change during the disease, because they reflect long-term non-specific immune stimulation rather than a specific immune response that during infectious disease changes (quantitatively and qualitatively).

INTRODUCTION In this study authors have analyzed the correlation between the IgG immunoglobulins in cerebrospinal fluid and the findings of oligoclonal bands on gel. Immunoglobulin IgG in cerebrospinal fluid (CSF) can be detected in neurological diseasses (infections and inflammatory neurological diseases and in demyelinating diseases, like multiple sclerosis (MS)). Quantitative IgG in CSF can be expressed by different formulae Reiber (Reiber and Felgenhauer 1987), Tourtellotte (Tourtellotte 1970), Schuller (Schuller and Sagar 1983) and IgG Index (Link and Tibbling 1977). In this study we used Reibergram. Qualitative CSF IgG can be measured by electrophoresis and isoelectric focusing (IEF). We used IEF for analysig CSF and seum because of its higher sensitivity. AIMS OF THE STUDY To determine the correlation of immunoglobulins IgG positivity in CSF with the finding of oligoclonal bands on the gel. MATERIAL AND METHODS The retrospective study based on data processed in OJ Clinical Immunology KCUS. Patients were suspicious of multiple sclerosis according to clinical findings and magnetic resonance imaging. All CSF and serum samples were processed by nephelometry, isoelectric focusing on the gel. Statistical analysis of intrathecal synthesis was also performed according to Reibergram. RESULTS Analyses were performed on 76 samples of cerebrospinal fluid and serum of patients from neurological clinic, suspected of multiple sclerosis. We received following results: 42 samples tested had type 1.25 samples tested showed type 2.3 samples had type 3.5 samples had type 4.1 sample had a fifth type. When we compare these results with values obtained by intrathecal synthesis of which is determined by Reibergram we obtained the following values: 16 samples had intrathecal synthesis of 20%-60%, 9 samples had a negative value of intrathecal synthesis of 10% or less. DISCUSSION AND CONCLUSION For most patients with established MS we found intrathecal humoral response, type two, and the number and arrangement of IgG bands generally does not change during the disease, because they reflect long-term non-specific immune stimulation rather than a specific immune response that during infectious disease changes (quantitatively and qualitatively).

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