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INTRODUCTION: Allergic rhinitis (AR) is a disease which affects >24% of the population in Russia. Triamcinolone acetonide (TAA) is a corticosteroid used for treating AR. This post hoc analysis assesses the efficacy of intranasal TAA in improving perennial AR (PAR) symptom scores over 4 weeks. METHODS: NASANIF (NCT03317015) was a double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial in which patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) over 4 weeks. Our post hoc analysis evaluates weekly change in PAR symptoms using the reflective Total Nasal Symptom Score (rTNSS), overall and for individual symptoms (sneezing, nasal itching, rhinorrhoea, and nasal obstruction). Proportion of patients and time to achieve a ≥50 or ≥75% reduction in rTNSS were assessed. For rTNSS endpoints, a linear mixed-model methodology was used; for time-to-event endpoints, cumulative incidence functions were estimated using the Kaplan-Meier method, in the per-protocol population. RESULTS: Of 260 patients, 128 each completed the study and were randomized to receive TAA or FP. From baseline to week 4, the changes in total rTNSS were -7.78 (95% CI: -8.1701 to -7.3967; p < 0.001) and -7.52 (-7.9053 to -7.1320; p < 0.001) for TAA and FP, respectively. Individual symptoms improved significantly from baseline. The proportion of patients achieving ≥50 and ≥75% reductions in total rTNSS was 88.0 and 67.2%, respectively in the TAA group. No significant differences were observed between the TAA and FP in any analyses. CONCLUSIONS: TAA produced effective and prolonged improvement of PAR symptoms over a 4-week treatment period.
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Anti-Inflamatórios/uso terapêutico , Imunossupressores/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Anti-Inflamatórios/farmacologia , Gerenciamento Clínico , Humanos , Imunossupressores/farmacologia , Estimativa de Kaplan-Meier , Prognóstico , Qualidade de Vida , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/etiologia , Federação Russa , Resultado do Tratamento , Triancinolona Acetonida/farmacologiaRESUMO
INTRODUCTION: Allergic rhinitis (AR) is a disease that affects ≤24% of people in Russia, significantly impairing quality of life (QoL). Intranasal corticosteroids, such as triamcinolone acetonide (TAA), are considered effective drugs for treatment. A post hoc analysis of data (phase III NASANIF trial) examined weekly QoL changes in patients receiving TAA for the treatment of perennial AR (PAR). METHODS: NASANIF (NCT03317015) was a double-blind, parallel group, multicenter, prospective, noninferiority, phase III clinical trial. Patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) for 4 weeks. Here, a post hoc analysis measures QoL using a shortened Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ). Differences in miniRQLQ score were evaluated using a mixed linear model and descriptive statistics. A subgroup analysis was performed in patients with a previous diagnosis of allergic conjunctivitis. RESULTS: Of 260 patients eligible for randomization, 128 each completed treatment with TAA or FP. Overall and individual domain scores progressively improved and were significantly different versus baseline at week 4 in both treatment groups: LS mean difference TAA: -30.92 (95% CI [-33.01 to -28.83]), p < 0.001, and FP: -31.13 (-33.23 to -29.04), p < 0.001. In both arms of the subgroup, there was a significant reduction in eye symptoms. There was no significant difference between the TAA and FP treatment groups in any analyses. CONCLUSIONS: TAA is effective in improving overall and individual domains of QoL in patients with PAR, over 4 weeks. Patients with a previous diagnosis of allergic conjunctivitis experienced significant improvements in QoL related to the resolution of these symptoms.
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Anti-Inflamatórios/uso terapêutico , Imunossupressores/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Anti-Inflamatórios/farmacologia , Gerenciamento Clínico , Humanos , Imunossupressores/farmacologia , Qualidade de Vida , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/etiologia , Resultado do Tratamento , Triancinolona Acetonida/farmacologiaRESUMO
A vaccine to protect against COVID-19 is urgently needed. Such a vaccine should efficiently induce high-affinity neutralizing antibodies which neutralize SARS-CoV-2, the cause of COVID-19. However, there is a concern regarding both vaccine-induced eosinophilic lung disease and eosinophil-associated Th2 immunopotentiation following infection after vaccination. Here, we review the anticipated characteristics of a COVID-19 vaccine to avoid vaccine-associated eosinophil immunopathology.
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Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Eosinófilos/fisiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Células Th2/imunologia , Vacinação/efeitos adversos , Vacinas Virais/efeitos adversos , Anticorpos Neutralizantes/biossíntese , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/imunologia , Humanos , SARS-CoV-2 , Vacinas Virais/imunologiaRESUMO
Eosinophils and their secretory mediators play an important role in the pathogenesis of infectious and inflammatory disorders. Although eosinophils are largely evolutionally conserved, their physiologic functions are not well understood. Given the availability of new eosinophil-targeted depletion therapies, there has been a renewed interest in understanding eosinophil biology as these strategies may result in secondary disorders when applied over long periods of time. Recent data suggest that eosinophils are not only involved in immunological effector functions but also carry out tissue protective and immunoregulatory functions that actively contribute to the maintenance of homeostasis. Prolonged eosinophil depletion may therefore result in the development of secondary disorders. Here, we review recent literature pointing to important roles for eosinophils in promoting immune defense, antibody production, activation of adipose tissue, and tissue remodeling and fibrosis. We also reflect on patient data from clinical trials that feature anti-eosinophil therapeutics.
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Eosinófilos/imunologia , Síndrome Hipereosinofílica/imunologia , Inflamação/imunologia , Animais , Formação de Anticorpos , Humanos , Imunidade Celular , Imunomodulação , Interleucina-5 , CicatrizaçãoRESUMO
BACKGROUND: Interrelation between thyrocytes and immunocytes has been established. However, the roles of mast cells and thyroid hormones in the triggering mechanism of thyroid autoimmune processes have been insufficiently investigated. This study evaluated the role of thyroid hormones and mast cells in the mechanisms of losing tolerance to thyroid autoantigens. MATERIALS AND METHODS: Two groups of patients were studied: patients with Graves' disease and patients with nodular euthyroid goiter. Wistar rats with induced exogenous hypothyroidism, thyrotoxicosis, and thyrotoxicosis in parallel with administration of interleukin-2 were used. The levels of hormones, autoantibodies, and cytokines in the serum and thyroid tissue were analyzed through the enzyme-linked immunosorbent assay. Morphological verification was performed through the immune-histochemical method with antibodies against tryptase and CD86. Transmission electron microscopy and laser confocal microscopy were used. RESULTS: In both Graves' disease and induced thyrotoxicosis, we detected a significant increase in the levels of interferon-γ, active interfollicular infiltration and degranulation of mast cells, and the intrathyroid overexpression of CD86. Complex analysis of the rat's thyroid morphofunctional state and systemic and local levels of cytokines in induced thyrotoxicosis and hypothyroidism demonstrated an increase of intrathyroid degranulation of mast cells and a drastic disruption of IFNγ/IL10 balance. CONCLUSIONS: When exposed to excessive amounts of thyroid hormones, an inflammatory response is triggered in the thyroid gland, and mast cells overexpress costimulating CD86 in the thyroid. This finding confirms their possible involvement in auto-antigen presentation. Significant increase in the levels of interferon-γ shows a determining influence of cytokine on the progression of the pathological process.
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Bócio Nodular/imunologia , Doença de Graves/imunologia , Mastócitos/imunologia , Glândula Tireoide/imunologia , Hormônios Tireóideos/metabolismo , Adulto , Animais , Autoantígenos/imunologia , Autoimunidade , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Tolerância Imunológica , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos , Ratos Wistar , Adulto JovemRESUMO
BACKGROUND: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide. OBJECTIVES: In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults. METHODS: In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events. RESULTS: The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: -8.2 ± 3.0 in the triamcinolone acetonide arm versus -8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide - fluticasone propionate) for rTNSS change from baseline was -0.2 (95% confidence interval -0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate. CONCLUSIONS: Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile.
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Antialérgicos/uso terapêutico , Fluticasona/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Administração Intranasal , Adulto , Alérgenos/imunologia , Antialérgicos/administração & dosagem , Feminino , Fluticasona/administração & dosagem , Humanos , Masculino , Qualidade de Vida , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/imunologia , Testes Cutâneos , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagemRESUMO
The expression of cytokine receptors has a crucial role in many cellular processes. Recent studies reported that changes of receptor expression could control the action of mediators on target cells. The initiation of different signaling pathways and, therefore, specific effects on cells, depends on certain components forming the cytokine-receptor complex. These mechanisms control the immune response and affect both the course of diseases (oncological, autoimmune, inflammatory) and the effectiveness of therapy. This review describes the potential of immune mediator receptors to regulate the efficiency of cytokine activity during pathologic processes and ensure the variability of their biological effects. Our aim was to investigate the spectrum of potential roles of changes in mediator receptor expression for main classes of pathologies. For all major types of immune mediators (cytokines, interleukins, chemokines, growth factors, and tumor necrosis factors), it has been shown that changes in their receptor expression are associated with impaired functioning of the organism in chronic diseases.
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Suscetibilidade a Doenças , Regulação da Expressão Gênica , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Biomarcadores , Humanos , ImunomodulaçãoRESUMO
Asthma is a chronic disabling respiratory disease that can be triggered by a variety of factors, including allergens, respiratory infections, psychological factors, occupational agents, exercise, atmospheric pollutants, and drugs. The asthma syndrome has been treated for decades according to a "one-fits-all" treatment strategy based on bronchodilators and steroids. With the availability of new forms of treatment targeting the different pathomechanisms of the asthma syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the interest in biomarkers that can dis criminate different forms of asthma according to their pathomechanisms has increased. This review attempts to provide an overview of protein biomarkers in asthma and how they might be used to discriminate different forms of asthma that may respond positively to sophisticated new targeted therapies.
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Asma/diagnóstico , Biomarcadores/metabolismo , Biomarcadores/análise , Humanos , Proteínas/análise , Proteínas/metabolismoRESUMO
BACKGROUND: Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (TNFα) is actively involved in inflammation processes in atopic dermatitis (AD), but the role of TNFα membrane receptors (TNFR) and their regulatory function in AD remains unclear. AIM: We aimed to determine the associations of parameters of TNFRα expression on immunocompetent cells with disease severity before and after therapy in AD patients. METHODS: TNFRα expression on T cells, B cells, and monocytes was evaluated by flow cytometry. To determine receptor numbers on the cells, Quantibrite PE beads were used. The content of soluble mediators was evaluated by ELISA. To reveal linear relationships between the index scoring AD (SCORAD) and the studied parameters, multiple linear regression model building was used. RESULTS: TNFR1 and TNFR2 expression in lymphocyte and monocyte populations of AD patients was higher than in healthy individuals (HI). At the same time an increased percentage of positive cells was not associated with high receptor density, and vice versa. Serum content of TNFα, both soluble receptors, the number of TNFR2/T cells, and the percentage of TNFR2+ monocytes were found to be strongly associated with the SCORAD index. CONCLUSION: AD patients had increased TNFR expression on immune cells. Changes in the parameters of TNFRα expression compared to HI were associated with the disease severity index SCORAD.
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Linfócitos B/imunologia , Dermatite Atópica/imunologia , Monócitos/imunologia , Receptores do Fator de Necrose Tumoral/metabolismo , Linfócitos T/imunologia , Adulto , Separação Celular , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Imunocompetência , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/genética , Índice de Gravidade de Doença , Regulação para Cima , Adulto JovemRESUMO
Introduction: The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment. Methods: In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests. Results: Sixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.
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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, potentially life-threatening syndromes characterized by the development of necrotic epidermal and mucosal lesions. The most common etiologic cause of SJS/TEN is drug-induced mechanisms. The group of drugs with high potential risk includes sulfonamides, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), allopurinol, phenobarbital, etc. There is no gold standard treatment algorithm for SJS/TEN. In medical practice, systemic glucocorticosteroids (sGCS), intravenous immunoglobulin (IVIG), plasmapheresis, and cyclosporine are used empirically and in various combinations. Recently published studies have demonstrated the efficacy of TNF-α inhibitors as a promising approach in SJS/TEN, including cases resistant to high-dose sGCS, with etanercept and infliximab being the most commonly used drugs. In a large multicenter study by Zhang J et al. (XXXX), 242 patients treated with etanercept, sGCS, or a combination of both had lower mortality compared to the control group. A shorter skin healing time was documented compared to sGCS monotherapy, thus reducing the risk of secondary infections. The published data show a high efficacy with THF-α inhibitor blockade, but the safety of TNF-α inhibitors in patients with SJS/TEN is still questionable due to the paucity of available information. As all clinical research data should be accumulated to provide reliable evidence that the use of TNF-α inhibitors may be beneficial in SJS/TEN, we report a case of etoricoxib-associated SJS with progression to TEN in a 50-year-old woman who was refractory to high-dose sGCS therapy.
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Several virus-neutralizing monoclonal antibodies (mAbs) have become new tools in the treatment of the coronavirus disease (COVID-19), but their effectiveness against the rapidly mutating virus is questionable. The present study investigated the effectiveness of Tixagevimab/Cilgavimab and Regdanvimab for mild and moderate COVID-19 treatment in real-world clinical practice during the Omicron variant-dominant period. Patients with known risk factors for disease progression and increasing disease severity were enrolled in the study within the first 7 days of symptom onset. Seventy-seven patients were divided into four groups: first 15 patients received 300 mg Tixagevimab/Cilgavimab intravenously (IV) and 23 patients got the same drug 300 mg intramuscularly (IM), the next 15 patients was on the same combination in dose of 600 mg IV, and 24 patients were on Regdanvimab at a dose of 40 mg/kg IV. By Day 4, 100% of Tixagevimab/Cilgavimab IV patients showed negative polymerase chain reaction results for SARS-CoV-2 Ribonucleic acid (RNA) regardless of the mAbs dose while in the Regdanvimab group 29% of the patients were positive for SARS-CoV-2 virus RNA. The testing for virus neutralizing antibodies (nAbs) to various Omicron sublineages (BA.1, BA.2, and BA.5) showed that an increase in nAb levels was detected in blood serum immediately after the drug administration only in Tixagevimab/Cilgavimab 300 mg and 600 mg IV groups. In the group of intravenous Regdanvimab, a significant increase in the level of nAbs to the Wuhan variant was detected immediately after the drug administration, while no increase in nAbs to different Omicron sublineages was observed. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05982704.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Humanos , Anticorpos Bloqueadores , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , RNA , SARS-CoV-2 , Resultado do TratamentoRESUMO
Cervical cancer is an important problem in women's health and a worldwide oncological disease. In 2018, the WHO registered 569,847 new cases in the world, and 3.4% were in the Russian Federation. We describe here a case of invasive cervical cancer stage IB2 associated with human papilloma virus in a woman who was treated by multicourse photodynamic therapy (PDT). A 38-year-old woman presented with abdominal pain and genital tract spotting in October 2015. Colposcopy revealed a neoplasm in cauliflower form. PAP smear result was cancer in situ (Tis). The biopsy result from the cervical canal and neoplasm was invasive squamous cell carcinoma. The patient underwent full preoperative examination (blood test, biochemical blood test, coagulation test, urinalysis, X-ray of chest organs, ECG, ultrasound investigation of pelvic organs, and PAP smear). Magnetic resonance imaging investigation showed a heterogeneous tumor, uneven contours, and intensity accumulating contrast. The patient was not pregnant, and a fertility-preserving treatment method was used. Three PDT sessions allowed to avoid vaginal radical trachelectomy. Pregnancy occurred 3 years and 8 months after the first PDT session. The patient had testing after treatment 4 times (3rd, 12th, 24th, and 60th months). She had a pregnancy without complications and had operative delivery by Cesarean section in April 2020. There was a 5-year remission period without episodes of relapse. The patient has an 8-month-old baby.
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BACKGROUND: Pandemic COVID-19 pneumonia due to SARS-2 is an important cause of morbidity and mortality. Emerging evidence links poor outcomes to an inflammatory cytokine storm. METHODS: We treated 89 hospitalized patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) with an infusion of tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor. RESULTS: Clinical and laboratory evidence of improvement was evident when baseline and 1-2-day post-infusion indices were compared. Among the 72 patients receiving supplemental oxygen without mechanical ventilation, severity of condition on the NEWS2 scale scores fell from 5 to 2 (P<0.001), C reactive protein levels fell from 95 to 14 mg/L (P<0.001), and lymphocyte counts rose from 900 to 1000/uL (P=0.036). Sixty-three of 72 patients were discharged from the hospital, one patient died, and eight patients remained in the hospital at the time of this writing. Among the 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (P=0.014) and early improvements in NEWS2 scores in 10 of 17 patients, 10 patients ultimately died and the other seven remain in the hospital at the time of this writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (<1000/uL) before TCZ administration. CONCLUSIONS: Inflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of tocilizumab, an anti-IL-6 receptor antibody, is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.
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Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses.
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Alérgenos/imunologia , Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Epitopos/imunologia , Imunidade , Animais , Anticorpos Bloqueadores/imunologia , Apresentação de Antígeno/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Dessensibilização Imunológica/métodos , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoglobulina E/imunologia , Memória Imunológica , Ativação Linfocitária/imunologia , Estações do Ano , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which were subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment. The percentage of CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer. Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The decrease in the total lymphocyte and T cell counts were associated with increased benzene exposure duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4+T cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive correlation between benzene toxicity and indicated increased immune responses, 45-day exposure to benzene appeared to be the most sensitive time point for evaluating benzene cytotoxicity.
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Benzeno/toxicidade , Imunidade Celular/efeitos dos fármacos , Baço/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Masculino , Ratos Wistar , Receptores de Antígenos de Linfócitos T/imunologia , Baço/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Fatores de TempoRESUMO
Common variable immunodeficiency (CVID) is a primary immunological disease characterized predominantly by hypogammaglobulinemia. The main clinical manifestations are severe recurrent infections that often lead to structural damage of affected organs. The early start of adequate intravenous immunoglobulin therapy has significantly improved the prognosis of this serious disorder. Patients with CVID are also predisposed to autoimmune and lymphoproliferative complications. This article deals with the features of this primary immunodeficiency in adults. Clinical manifestations, immunological features and treatment concepts were gathered during 21 years of observation of such patients in Moscow. The authors suggest early predictive clinical signs of CVID in adults.
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The choice of a preparation for selective correction and the solution to the question of how long immunotherapy should be carried out compose a complicated problem in view of the fact that in the majority of cases an attempt to treat any "main defect" of immune response in somatic patients is not possible. Immunomodulators by origin may be conditionally divided into endogenous and exogenous. Endogenous preparations combine interleukins, lymphokines, monokines, interferons, thymus hormones and some other substances which are present in a human organism and take part in the regulation of immune reactions. Use of this class of immunomodulators relates to a sufficiently wide spectrum of diseases, including of infectious and autoimmune pathology. Long-term fundamental studies of synthetic stimulators of immunity ended with the creation of a new immunomodulators - polyoxidonium, licopid and ribomunil. This preparations have a wide spectrum of immunopharmacological action. Of importance, from the point of view of clinical immunology, is the development of the principles of combined immunocorrection and the creation of a new approach - immunorehabilitation. The use of different immunomodulating preparations and antibiotics, hormones, cytostatics and other medicinal agents, having immunocorrecting properties is justified and sufficiently effective.
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The object of this work was to study (i) the effect of monoclonal antibodies (mAb) to a receptor (R) of an oncofetal protein of an alpha-fetoprotein (AFP) on the survival rate and sensitivity of tumor target cells to the cytotoxic action of effector cells, (ii) the level of Ab to AFP-R in the blood serum of patients with malignant tumors (iii) the effect of blood serum with a high level of Ab to AFP-R on the survival rate of tumor cells in vitro, and also (iv) the effect of immunization of animals with an AFP-R preparation on subsequent development of a grafted tumor. It is shown that mAb to AFP-R of clones 2E1, 5C6 and 2B8 effectively bond to both mouse tumor cells and to human tumor cells. Monoclonal Ab to AFP-R of the studied clones do not affect the proliferation of tumor cells of mice and insignificantly inhibit the proliferation of human tumor cells. In patients with malignant tumors, a substantial increase was detected of both the sum Ab to AFP-R, and Ab of the class IgM, and simultaneously an increase of the fraction Ab to AFP-R of the class IgM, which indicates the induction of a primary immune response to AFP-R in such patients. Separate clones of mAb to AFP-R are capable of activating the immune system in respect to tumor cells, inducing of antibody-dependent cellular cytotoxic activity, but with an increase of the concentration of mAb to AFP-R to 1 &mgr;M, the blocking of the cytotoxic activity of peripheral blood mononuclear cells in respect to human tumor cells is possible. In the case of single immunization of mice with an AFP-R preparation, isolated from tumor tissue of lung cancer of a human, inhibition of the growth of a tumor, grafted four days after the immunization, was observed.