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Browsing by Author "Bonaci-Nikolic, Branka (10839652200)"

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    Assessment of Deoxyribonuclease Activity in Serum Samples of Patients With Systemic Lupus Erythematosus: Fluorescence-Based Method Versus ELISA
    (2016)
    Vancevska, Aleksandra (55812981100)
    ;
    Nikolic, Aleksandra (57194842918)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Skiljevic, Dusan (23487265400)
    ;
    Radojkovic, Dragica (6602844151)
    Background: We report the improvement of previously described method for determining deoxyribonuclease (DNase) activity in serum samples that uses a fluorescently labeled DNA fragment as a substrate. Methods: Activity of serum DNase was analyzed in 31 patients with systemic lupus erythematosus (SLE) and 13 healthy individuals by fluoresence-based method and ELISA test. Results: We found a mean decrease in DNase activity between cases and controls of 12.46% measured by the fluoresence-based method and of 12.21% measured by ELISA method. High level of positive correlation between two methods for DNase activity was observed: P < 0.001 and Pearson correlation coefficient 0.740. Decreased DNase activity was found in 25 of 31 SLE patients (81%) by fluoresence-based method and in 24 of 31 SLE patients (77%) by ELISA test. We also observed the significant positive correlation between titer of anti-dsDNA antibodies and DNase activity measured by both methods (P < 0.05). Conclusions: The key improvement is the use of internal control in the fluorescence-based method, which diminishes the influence of technical errors on the obtained results and increases reliability of the assay. This improved fluorescence-based method, with additional validation, may provide an alternative to more expensive and time-consuming conventional methods, such as ELISA. © 2016 Wiley Periodicals, Inc.
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    Assessment of Deoxyribonuclease Activity in Serum Samples of Patients With Systemic Lupus Erythematosus: Fluorescence-Based Method Versus ELISA
    (2016)
    Vancevska, Aleksandra (55812981100)
    ;
    Nikolic, Aleksandra (57194842918)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Skiljevic, Dusan (23487265400)
    ;
    Radojkovic, Dragica (6602844151)
    Background: We report the improvement of previously described method for determining deoxyribonuclease (DNase) activity in serum samples that uses a fluorescently labeled DNA fragment as a substrate. Methods: Activity of serum DNase was analyzed in 31 patients with systemic lupus erythematosus (SLE) and 13 healthy individuals by fluoresence-based method and ELISA test. Results: We found a mean decrease in DNase activity between cases and controls of 12.46% measured by the fluoresence-based method and of 12.21% measured by ELISA method. High level of positive correlation between two methods for DNase activity was observed: P < 0.001 and Pearson correlation coefficient 0.740. Decreased DNase activity was found in 25 of 31 SLE patients (81%) by fluoresence-based method and in 24 of 31 SLE patients (77%) by ELISA test. We also observed the significant positive correlation between titer of anti-dsDNA antibodies and DNase activity measured by both methods (P < 0.05). Conclusions: The key improvement is the use of internal control in the fluorescence-based method, which diminishes the influence of technical errors on the obtained results and increases reliability of the assay. This improved fluorescence-based method, with additional validation, may provide an alternative to more expensive and time-consuming conventional methods, such as ELISA. © 2016 Wiley Periodicals, Inc.
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    Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, in patients with gluten-sensitive enteropathy: A possible serological trap
    (2012)
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Spuran, Milan (6505943315)
    ;
    Andrejevic, Sladjana (6701472920)
    ;
    Nikolic, Milos (56910382000)
    [No abstract available]
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    Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, in patients with gluten-sensitive enteropathy: A possible serological trap
    (2012)
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Spuran, Milan (6505943315)
    ;
    Andrejevic, Sladjana (6701472920)
    ;
    Nikolic, Milos (56910382000)
    [No abstract available]
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    Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity
    (2022)
    Stjepanovic, Mihailo I. (55052044500)
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    Stojanovic, Maja R. (57201074079)
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    Stankovic, Sanja (7005216636)
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    Cvejic, Jelena (58810863700)
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    Dimic-Janjic, Sanja (57208444020)
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    Popevic, Spasoje (54420874900)
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    Buha, Ivana (44460972900)
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    Belic, Slobodan (57222640039)
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    Djurdjevic, Natasa (57202011285)
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    Stjepanovic, Mirjana M. (56716026000)
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    Jovanovic, Dragana (7102247807)
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    Stojkovic-Laloševic, Milica (57218133245)
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    Soldatovic, Ivan (35389846900)
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    Bonaci-Nikolic, Branka (10839652200)
    ;
    Miskovic, Rada (56394650000)
    Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome. Copyright © 2022 Stjepanovic, Stojanovic, Stankovic, Cvejic, Dimic-Janjic, Popevic, Buha, Belic, Djurdjevic, Stjepanovic, Jovanovic, Stojkovic-Laloševic, Soldatovic, Bonaci-Nikolic and Miskovic.
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    Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia
    (2024)
    Miskovic, Rada (56394650000)
    ;
    Ljubicic, Jelena (57209233078)
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    Bonaci-Nikolic, Branka (10839652200)
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    Petkovic, Ana (57394209800)
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    Markovic, Vladana (55324145700)
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    Rankovic, Ivan (57192091879)
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    Djordjevic, Jelena (58458535700)
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    Stankovic, Ana (57197902801)
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    Klaassen, Kristel (54959837700)
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    Pavlovic, Sonja (7006514877)
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    Stojanovic, Maja (57201074079)
    Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer’s disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation. Copyright © 2024 Miskovic, Ljubicic, Bonaci-Nikolic, Petkovic, Markovic, Rankovic, Djordjevic, Stankovic, Klaassen, Pavlovic and Stojanovic.
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    Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia
    (2024)
    Miskovic, Rada (56394650000)
    ;
    Ljubicic, Jelena (57209233078)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Petkovic, Ana (57394209800)
    ;
    Markovic, Vladana (55324145700)
    ;
    Rankovic, Ivan (57192091879)
    ;
    Djordjevic, Jelena (58458535700)
    ;
    Stankovic, Ana (57197902801)
    ;
    Klaassen, Kristel (54959837700)
    ;
    Pavlovic, Sonja (7006514877)
    ;
    Stojanovic, Maja (57201074079)
    Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer’s disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation. Copyright © 2024 Miskovic, Ljubicic, Bonaci-Nikolic, Petkovic, Markovic, Rankovic, Djordjevic, Stankovic, Klaassen, Pavlovic and Stojanovic.
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    Childhood microscopic polyangiitis associated with MPO-ANCA
    (2006)
    Peco-Antic, Amira (7004525216)
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    Bonaci-Nikolic, Branka (10839652200)
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    Basta-Jovanovic, Gordana (6603093303)
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    Kostic, Mirjana (56247970900)
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    Markovic-Lipkovski, Jasmina (6603725388)
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    Nikolic, Milos (56910382000)
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    Spasojevic, Brankica (10839232100)
    We reviewed the clinical, histological and serological parameters of microscopic polyangiitis (MPA) associated with antineutrophil cytoplasmic antibodies (ANCA) specific to myeloperoxidase (MPO). Six girls and one boy aged 12.0±2.6 years (7-15 years) met the following inclusion criteria: (1) clinical manifestations of systemic small vessel involvement; (2) histological demonstration of pauci-immune necrotizing glomerulonephritis; and (3) serological findings of increased concentration of MPO-ANCA by ELISA test. The main clinical manifestations were: influenza-like symptoms (100%), hematuria/ proteinuria (100%), purpura (100%), pulmonary-renal syndrome (57%), acute renal failure (ARF) (29%), ischemic cerebral insults (29%), and necrotizing vasculitis of the skin (29%). All patients underwent renal biopsy examined by immunohistochemistry with expression of alpha-smooth muscle actin (alpha SMA) in glomerular and interstitial spaces. Patients were followed from 6 months to 5.5 years (35.4±23.2 months). None of the patients died. Two of seven children who had ARF progressed to end stage renal disease; one developed chronic renal failure, and four normalized renal function. ARF and central nervous system involvement at presentation were parameters of poor renal outcome. A high score of fibro-cellular glomerular crescents was associated with worse prognosis. Early treatment enables a favorable prognosis of MPO-ANCA-associated MPA in children. © IPNA 2005.
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    Combined intravenous pulse and topical corticosteroid therapy for severe alopecia areata in children: Comparison of two regimens
    (2019)
    Lalosevic, Jovan (57190969635)
    ;
    Gajic-Veljic, Mirjana (24767639800)
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    Bonaci-Nikolic, Branka (10839652200)
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    Stojkovic Lalosevic, Milica (57218133245)
    ;
    Nikolic, Milos (56910382000)
    There is no universally accepted treatment for severe pediatric alopecia areata (AA). This prospective study comprised 73 patients (aged 1–18 years) with severe AA (>30% of scalp surface area): 37 received 1-day intravenous dexamethasone pulses (1-DP) and 36 received 3-day pulses (3-DP), monthly, for 6–12 months. Also, all patients applied topical clobetasol propionate under plastic wrap occlusion. Patients achieving >50% regrowth were considered good responders (GR). All patients reached short term, while 65/73 were available for the long-term follow-up (mean 33.3 ± 15.3 vs. 27.7 ± 14.3 months, 1-DP and 3-DP, respectively). Relapses during therapy were more frequent in 1-DP group. 3-DP patients were more frequently GR in comparison with 1-DP. 3-DP patients with disease duration <6 months had better outcomes. Patients without Hashimoto thyroiditis (HT) had 9.8-fold higher chance of being GR in comparison with HT patients. The best results were achieved in AA plurifocalis (AAP). No patient had severe short-term side-effects. At the long-term follow-up, 67% of 3-DP patients had stable results. Only 14.2% AAP patients experienced relapses. Patients had no long-term side-effects. 3-DP were more efficacious than 1-DP. Short disease duration and no HT were good prognostic factors. 3-DP protocol is well-tolerated, with beneficial effects and long-lasting results in severe pediatric AA. © 2019 Wiley Periodicals, Inc.
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    Combined oral pulse and topical corticosteroid therapy for severe alopecia areata in children: A long-term follow-up study
    (2015)
    Lalosevic, Jovan (57190969635)
    ;
    Gajic-Veljic, Mirjana (24767639800)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Nikolic, Milos (56910382000)
    There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty-three percent of patients had AA plurifocalis (AAP). Fifty-seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long-term follow-up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0-100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long-term follow-up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long-lasting results, without serious side effects. © 2015 Wiley Periodicals, Inc.
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    Concomitant drug-and infection-induced antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis with multispecific ANCA
    (2012)
    Kontic, Milica (43761339600)
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    Radovanovic, Sanja (56432618100)
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    Nikolic, Milos (56910382000)
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    Bonaci-Nikolic, Branka (10839652200)
    Objective: To report the first case of concomitant drug-and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis. Presentation and Intervention: A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs. Conclusion: Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU-and M. tuberculosis-induced AAV. Copyright © 2012 S. Karger AG, Basel.
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    Cryoglobulins and multispecific antineutrophil cytoplasmic antibodies in propylthiouracil- induced necrotizing cutaneous vasculitis - a new association
    (2012)
    Zivanovic, Dubravka (24170307900)
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    Dobrosavljevic, Danijela (21133925200)
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    Nikolic, Milos (56910382000)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    [No abstract available]
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    Developing COVID-19 vaccine recommendations during the pandemic: The experience of Serbia's Expert Committee on Immunization
    (2022)
    Markovic-Denic, Ljiljana (55944510900)
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    Popadic, Dusan (6602255798)
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    Jovanovic, Tanja (26642921700)
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    Bonaci-Nikolic, Branka (10839652200)
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    Samardzic, Janko (23987984500)
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    Tomic Spiric, Vesna (6603500319)
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    Rancic, Miljan (57992502100)
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    Sankar Datta, Siddhartha (57217159355)
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    Mosina, Liudmila (43161421300)
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    Jancic, Jasna (35423853400)
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    Vukomanovic, Goran (8252832300)
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    Jovanovic, Verica (56566176800)
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    Vukomanovic, Vladislav (55881072000)
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    Antic, Darko (23979576100)
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    Veljkovic, Marko (57188659157)
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    Saponjic, Vladan (57730308500)
    ;
    Jacques-Carroll, Lisa (24528511600)
    A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provide evidence-based recommendations to policy-makers to assist them in making informed immunization policy and programme decisions. During the COVID-19 pandemic, NITAGs faced many challenges in making evidence-based recommendations for COVID-19 vaccines due to the rapidly evolving situation with new vaccine products available in a short time period and limited data on vaccine effectiveness. The authors reviewed the process used by Serbia's NITAG, which is called the Serbian Expert Committee on Immunization, to develop COVID-19 vaccine recommendations during the pandemic. The article examines the challenges and successes faced by the committee. Serbia's expert committee used the best available evidence to develop over forty recommendations on all aspects of COVID-19 vaccination. These expert committee recommendations facilitated the early procurement and successful roll-out of COVID-19 vaccines, guidance for vaccination of individuals at the highest risk, and high COVID-19 vaccination coverage in the country. The availability of five COVID-19 vaccines in Serbia was an advantage for the successful roll-out but posed challenges for the expert committee. Serbia's expert committee plans to use the experience and best practices developed during the pandemic to improve and expand its work moving forward. Copyright © 2022 Markovic-Denic, Popadic, Jovanovic, Bonaci-Nikolic, Samardzic, Tomic Spiric, Rancic, Sankar Datta, Mosina, Jancic, Vukomanovic, Jovanovic, Vukomanovic, Antic, Veljkovic, Saponjic and Jacques-Carroll.
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    Evaluation of cytokine genetic polymorphisms in adult patients with common variable immunodeficiency: A single-center study
    (2016)
    Perovic, Dijana (55251514500)
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    Perovic, Vladimir (57197980665)
    ;
    Pravica, Vera (7003322504)
    ;
    Bonaci-Nikolic, Branka (10839652200)
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    Mijanovic, Radovan (57015560200)
    ;
    Bunjevacki, Vera (6506110754)
    Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by impaired B-cell differentiation and maturation accompanied with the defective antibody production. Several investigators addressed the possibility that disturbed cytokine production of TNF, IL-6, IFN-γ and IL-10, among a variety of others, may be implicated in CVID. The aim of this study was to test the hypothesis that genetic polymorphisms involving TNF (−308G/A), IFNG (+874 T/A), IL10 (−1082G/A, −819T/C and −592A/C), and IL6 (−174G/C) cytokine genes might contribute to susceptibility to CVID. Thirty five patients with CVID and 250 healthy controls were genotyped for indicated single nucleotide polymorphisms (SNP) in TNF, IL6, IFNG and IL10 using Taqman-based assays. CVID patients had significantly higher frequency of TNF A allele and AA genotype than in healthy subjects (p = 0.006; OR = 2.27; 95%CI = 1.24-4.17 and p = 0.038, OR = 15.64; 95%CI = 1.38-177.20, respectively). In addition, the frequency of GG genotype was significantly higher in healthy controls than in patient group (p = 0.019, OR = 0.43, 95%CI = 0.21-0.89). Genetic analysis of IL6 SNP showed that allele G confers increased risk for CVID (p = 0.037, OR = 1.78, 95% CI = 1.03-3.08) while IFNG allele T was associated with splenomegaly in CVID (p = 0.032; OR = 2.86; 95% CI = 1.08-7.56). We observed no association between genotypes, alleles and haplotypes of IL-10 gene and CVID or its clinical complications. In conclusion, our results indicated association between CVID and cytokine gene polymorphisms −308 G/A TNF and −174G/C IL6. In addition, we demonstrated that splenomegaly, one of the most common complications in this disease, is associated with +874T/A IFNG polymorphism. These findings add further support to the notion that cytokines may play significant role in pathogenesis of this primary antibody deficiency. However, further investigation that would involve a larger study group of CVID patients is warranted to confirm our findings. © 2016 European Federation of Immunological Societies
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    Evaluation of cytokine genetic polymorphisms in adult patients with common variable immunodeficiency: A single-center study
    (2016)
    Perovic, Dijana (55251514500)
    ;
    Perovic, Vladimir (57197980665)
    ;
    Pravica, Vera (7003322504)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Mijanovic, Radovan (57015560200)
    ;
    Bunjevacki, Vera (6506110754)
    Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by impaired B-cell differentiation and maturation accompanied with the defective antibody production. Several investigators addressed the possibility that disturbed cytokine production of TNF, IL-6, IFN-γ and IL-10, among a variety of others, may be implicated in CVID. The aim of this study was to test the hypothesis that genetic polymorphisms involving TNF (−308G/A), IFNG (+874 T/A), IL10 (−1082G/A, −819T/C and −592A/C), and IL6 (−174G/C) cytokine genes might contribute to susceptibility to CVID. Thirty five patients with CVID and 250 healthy controls were genotyped for indicated single nucleotide polymorphisms (SNP) in TNF, IL6, IFNG and IL10 using Taqman-based assays. CVID patients had significantly higher frequency of TNF A allele and AA genotype than in healthy subjects (p = 0.006; OR = 2.27; 95%CI = 1.24-4.17 and p = 0.038, OR = 15.64; 95%CI = 1.38-177.20, respectively). In addition, the frequency of GG genotype was significantly higher in healthy controls than in patient group (p = 0.019, OR = 0.43, 95%CI = 0.21-0.89). Genetic analysis of IL6 SNP showed that allele G confers increased risk for CVID (p = 0.037, OR = 1.78, 95% CI = 1.03-3.08) while IFNG allele T was associated with splenomegaly in CVID (p = 0.032; OR = 2.86; 95% CI = 1.08-7.56). We observed no association between genotypes, alleles and haplotypes of IL-10 gene and CVID or its clinical complications. In conclusion, our results indicated association between CVID and cytokine gene polymorphisms −308 G/A TNF and −174G/C IL6. In addition, we demonstrated that splenomegaly, one of the most common complications in this disease, is associated with +874T/A IFNG polymorphism. These findings add further support to the notion that cytokines may play significant role in pathogenesis of this primary antibody deficiency. However, further investigation that would involve a larger study group of CVID patients is warranted to confirm our findings. © 2016 European Federation of Immunological Societies
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    Evaluation of National Immunization Technical Advisory Groups (NITAGs) of middle-income countries in the WHO European Region; a synopsis
    (2025)
    Külper-Schiek, Wiebe (57221281676)
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    Mosina, Liudmila (43161421300)
    ;
    Jacques-Carroll, Lisa A. (24528511600)
    ;
    Falman, Annika (59224927900)
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    Harder, Thomas (56219301200)
    ;
    Kakarriqi, Eduard (6507421093)
    ;
    Preza, Iria (56015878800)
    ;
    Badalyan, Arman (57210846796)
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    Sahakyan, Gayane (54789259400)
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    Romanova, Oxana (57216617969)
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    Shimanovich, Veronika (58382091100)
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    Musa, Sanjin (55748266100)
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    Bayesheva, Dinagul (57189647628)
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    Azimbayeva, Nurshay (59676642000)
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    Nurmatov, Zuridin (39863304600)
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    Toigombaeva, Vera (56904169700)
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    Revenco, Ninel (57219970548)
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    Gutu, Veaceslav (57210358425)
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    Markovic-Denic, Ljiljana (55944510900)
    ;
    Bonaci-Nikolic, Branka (10839652200)
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    Tursunova, Dilorom (16949769700)
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    Tadzhiyeva, Nigora (59677207500)
    ;
    Wichmann, Ole (6603891996)
    ;
    Datta, Siddhartha Sankar (55538126700)
    Introduction: A National Immunization Technical Advisory Group (NITAG) provides independent guidance to Ministries of Health (MoH) and policymakers, enabling them to make informed decisions on national immunization policies and practices. As of 2022, 50 of the 53 countries in the World Health Organization (WHO) European Region (the Region) had established a NITAG, with 58% of all NITAGs and 66% of those in middle-income countries (MICs) in the Region meeting all six WHO process indicators of NITAG functionality. However, many newly established NITAGs in MICs in the Region experience challenges in terms of their functioning, structure, and outputs. Methods: To address these challenges and achieve the goal of evidence-informed decision making on immunizations, the WHO Regional Office for Europe and the Robert Koch Institute (RKI) implemented a project to strengthen the functioning of MIC NITAGs of the Region through comprehensive evaluations of nine NITAGs and development and implementation of improvement plans. Results: All evaluated NITAGs are formally established and complete the most important aspects of NITAG functioning. The main challenge for all NITAGs is the lack of a well-staffed Secretariat to establish annual workplans and develop NITAG recommendations following a standardized process. Discussion: The evaluation identified NITAGs' strengths and challenges. Some challenges have been addressed through improvement plan implementation. WHO and RKI will continue to evaluate NITAGs and support development and implementation of improvement plans. WHO and NITAG partners will continue to provide training on the standardized recommendation-making process and advocate increased MoH support to NITAGs, including dedicated Secretariat staff. Copyright © 2025 Külper-Schiek, Mosina, Jacques-Carroll, Falman, Harder, Kakarriqi, Preza, Badalyan, Sahakyan, Romanova, Shimanovich, Musa, Bayesheva, Azimbayeva, Nurmatov, Toigombaeva, Revenco, Gutu, Markovic-Denic, Bonaci-Nikolic, Tursunova, Tadzhiyeva, Wichmann and Datta.
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    Granulomatosis with polyangiitis (wegener's granulomatosis) in children: Report of three cases with cutaneous manifestations and literature review
    (2013)
    Gajic-Veljic, Mirjana (24767639800)
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    Nikolic, Milos (56910382000)
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    Peco-Antic, Amira (7004525216)
    ;
    Bogdanovic, Radovan (7004665744)
    ;
    Andrejevic, Sladjana (6701472920)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis, is a rare disease in childhood. Of 39 GPA patients that we diagnosed during a 20-year period, only 3 (7.7%) were younger than 18 years. We report the course of GPA in three girls whose disease started at the ages of 16, 11, and 6 years. All had cutaneous manifestations: the first had necrotizing vasculitis, the second had palpable purpura, and the third had right upper-eyelid edema and infiltration and proptosis caused by extraocular pseudotumor, initially histologically misdiagnosed as orbital immunoglobulin G4 (IgG4)-related disease. Unlike with skin vasculitis and glomerulonephritis, upper-airway and orbital inflammation were resistant to immunosuppressive therapy. Our report emphasizes that children presenting with cutaneous vasculitis, chronic eyelid swelling, sinusitis, or hoarseness should be tested for antineutrophil cytoplasmic antibodies. We emphasize that the upper-eyelid edema and infiltration, with histologic characteristics of orbital IgG4-related disease, may be the initial presentation of localized GPA in children, a feature that, until now, has been described only in adults. © 2012 Wiley Periodicals, Inc.
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    HCV related severe cryoglobulinemic vasculitis treated with plasma exchange and rituximab: Case report and literature review
    (2017)
    Arandjelovic, Snezana (19533573900)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Peric-Popadic, Aleksandra (6603261722)
    ;
    Tomic-Spiric, Vesna (6603500319)
    ;
    Bolpacic, Jasna (6507378541)
    ;
    Raskovic, Sanvila (6602461528)
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    Andrejevic, Sladjana (6701472920)
    Mixed cryoglobulinemia is the most prevalent extrahepatic manifestation of chronic HCV infection. It is usually a benign lymphoproliferative disorder which presents as vasculitis affecting different organs. Although life-threatening cryoglobulinemic vasculitis (CryoVas) is rare, it is sometimes the first and possibly lethal complication. Its treatment depends on the severity of vasculitis and can be challenging. High dose of corticosteroids, immunosuppressive agents and plasma exchange represent the first-line treatment, which should be followed by antiviral therapy. Rituximab is an effective and safe treatment option. However, the data about its use in life-threatening conditions are scarce. We report the case of a patient with severe, relapsing and life-threatening HCV-related CryoVas resistant to standard therapy who had had an initial beneficial response to rituximab added to plasma exchange that was later compromised by the development of sepsis. We also review the literature and discuss manifestations and therapy of life-threatening Cryovas with focus on rituximab use. © 2017 Arandjelovic et al.
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    HCV related severe cryoglobulinemic vasculitis treated with plasma exchange and rituximab: Case report and literature review
    (2017)
    Arandjelovic, Snezana (19533573900)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    ;
    Peric-Popadic, Aleksandra (6603261722)
    ;
    Tomic-Spiric, Vesna (6603500319)
    ;
    Bolpacic, Jasna (6507378541)
    ;
    Raskovic, Sanvila (6602461528)
    ;
    Andrejevic, Sladjana (6701472920)
    Mixed cryoglobulinemia is the most prevalent extrahepatic manifestation of chronic HCV infection. It is usually a benign lymphoproliferative disorder which presents as vasculitis affecting different organs. Although life-threatening cryoglobulinemic vasculitis (CryoVas) is rare, it is sometimes the first and possibly lethal complication. Its treatment depends on the severity of vasculitis and can be challenging. High dose of corticosteroids, immunosuppressive agents and plasma exchange represent the first-line treatment, which should be followed by antiviral therapy. Rituximab is an effective and safe treatment option. However, the data about its use in life-threatening conditions are scarce. We report the case of a patient with severe, relapsing and life-threatening HCV-related CryoVas resistant to standard therapy who had had an initial beneficial response to rituximab added to plasma exchange that was later compromised by the development of sepsis. We also review the literature and discuss manifestations and therapy of life-threatening Cryovas with focus on rituximab use. © 2017 Arandjelovic et al.
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    Immunoserological parameters in SLE: High-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity
    (2013)
    Andrejevic, Sladjana (6701472920)
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    Jeremic, Ivica (36016708800)
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    Sefik-Bukilica, Mirjana (8118591400)
    ;
    Nikolic, Milos (56910382000)
    ;
    Stojimirovic, Biljana (7004273397)
    ;
    Bonaci-Nikolic, Branka (10839652200)
    We assessed the relationship between the serum levels of antibodies against double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement components with one another, with organ involvement and overall disease activity in patients with systemic lupus erythematosus (SLE). One hundred seventy-five sera from 99 patients with SLE, 31 sera of patients with other connective tissue diseases, and 20 sera from healthy blood donors were tested. SLE disease activity was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most significant risk factor for renal involvement were anti-C1q antibodies (OR = 3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99, p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05), and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR = 3.32, p < 0.01). Multiple linear regression analysis showed that disease activity in SLE could be predicted by the levels of antibodies against dsDNA determined by standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti-dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K. Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5) (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies represented a risk for renal, joint, and most importantly for serosal involvement. Our results suggest that simple and reliable ELISA for high-avidity anti-dsDNA antibodies is the test of good clinical utility for the assessment of global SLE activity. © 2013 Clinical Rheumatology.
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