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Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes.Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.
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BACKGROUND: Natural killer cells (NK) and innate lymphoid cells with their subsets (ILC) are part of the innate immune system. OBJECTIVE: The aim is to evaluate how NK cells and ILC cells interact in atopic dermatitis (AD) patients (with and without dupilumab therapy) compared to control group. MATERIALS AND METHODS: Complete dermatological examination was performed in all patients included in the study (19 AD patients with dupilumab, 17 AD patients without dupilumab). Surface molecules expressed on NK cells and ILC cells were analyzed by flow cytometry. The association between NK cells and total ILC cells, ILC-1, ILC-2, ILC-3, NCR+ILC3, NCR-ILC3 were compared in AD patients and in the control group. The non-parametric Spearman's rank correlation coefficient was used for this statistical analysis. We evaluated the association of parameters with AD severity at the time of treatment.Non-parametric Mann-Whitney, Kolmogorov-Smirnov tests were used. RESULTS: We confirmed the higher association between NK cells and total ILC cells in AD patients without dupilumab therapy (in 30.3 %) and in healthy controls (in 27.2 %); this association is low in AD patients with dupilumab therapy (in 0.1 %). The higher association was confirmed between NK cells and ILCs subsets only in AD patients without dupilumab therapy; in these patients the highest association was confirmed between NK cells and ILC-2 cells (in 38.6 %). No statistically significant difference in the count of NK cells and ILC cells was found between mild and moderate form of AD patients treated with dupilumab. CONCLUSION: Targeting these cell types or the cytokines they produce could represent potential therapeutic strategies for controlling inflammation and alleviating symptoms in AD patients.
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Anticorpos Monoclonais Humanizados , Dermatite Atópica , Células Matadoras Naturais , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Imunidade Inata/efeitos dos fármacos , Adulto Jovem , Linfócitos/imunologia , Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Comunicação CelularRESUMO
Neutrophils are frequently found in the cytological picture of synovial fluid in several joint pathologies, and a higher proportion of them can even wrongly indicate these cases as purulent inflammation. For reliable differentiation between purulent and non-purulent cases, we use the cytological energy analysis of the synovial fluid. Using this method, we examined 350 knee joint synovial fluid samples. Overall, we found that the percentage of neutrophils ranged between 20.0% and 50.0% in 44 (12.6%) cases and was above 50.0% in 231 (66.0%) cases. In the same group, only 85 (24.3%) highly anaerobic synovial fluid samples were evaluated as purulent inflammation, and another 17 (4.9%) cases were evaluated as very likely purulent inflammation. Further, we quantified the immediate risk of purulent inflammation using the "purulent score" (PS). Of the total of 350 samples, 103 (29.4%) cases were classified as having a very high risk of purulent inflammation (PS = 4), 53 (15.1%) cases were classified as having a significant risk of purulent inflammation (PS = 3), 17 (4.9%) cases were classified as having a moderate risk of purulent inflammation (PS = 2), and 75 (21.4%) cases were classified as having no immediate risk of purulent inflammation (PS = 1). Based on our results and analyses, the cytological energy analysis of synovial fluid is an effective method that can be used to detect and specify joint inflammation and the risk of septic arthritis development.
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Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.
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Dermatite Atópica , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/etiologia , Dermatite Atópica/terapia , Pele , Resultado do Tratamento , Epiderme/patologia , AnsiedadeRESUMO
The aim of this study was to conduct QuantiFERON Monitor (QFM) testing in patients with multiple sclerosis (MS), which is used to monitor the state of the immune system through the non-specific stimulation of leukocytes followed by determining the level of interferon-gamma (IFN-γ) released from activated cells. Additionally, we tested the level of selected cytokines (IFN-α, IFN-γ, IL-1α, IL-1ß, IL-1ra, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IL-15, IL-33, VEGF) from stimulated blood samples to further understand the immune response. This study builds upon a previously published study, utilizing activated serum samples that were initially used for IFN-γ determination. However, our current focus shifts from IFN-γ to exploring other cytokines that could provide further insights into the immune response. A screening was conducted using Luminex technology, which yielded promising results. These results were then further elaborated upon using ELISA to provide a more detailed understanding of the cytokine profiles involved. This study, conducted from August 2019 to June 2023, included 280 participants: 98 RRMS patients treated with fingolimod (fMS), 96 untreated patients with progressive MS (pMS), and 86 healthy controls (HC). Our results include Violin plots showing elevated IL-1α in pMS and fMS. Statistical analysis indicated significant differences in the interleukin levels between groups, with IL-1ra and age as key predictors in differentiating HC from pMS and IL-1ra, IL-1α, age, and EDSS in distinguishing pMS from fMS. These findings suggest cytokines' potential as biomarkers in MS progression and treatment response.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Proteína Antagonista do Receptor de Interleucina 1 , Citocinas , Interferon gama , Sistema ImunitárioRESUMO
OBJECTIVE: The aim of the study is to analyze the absolute count of leukocytes, neutrophils, monocytes, eosinophils, T cells, natural killer cells, B cells and to evaluate the expression of functionally important CD23 and CD200 molecules on B cells in patients suffering from atopic dermatitis (AD), (with and without dupilumab therapy). MATERIALS AND METHODS: We examined 45 patients suffering from AD - 32 patients without dupilumab treatment (10 men, 22 women, average age 35.0 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years) and 30 healthy control (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry (Navios Flow Cytometer - Beckman Coulter). The blood count was examined with a Sysmex XN 3000, Sysmex SP10, microscope DI60 for digital morphology evaluating cell division and microscope Olympus BX40. We compared the absolute count of leukocytes and their subsets, T cells (CD4, CD8), natural killers cells, absolute and relative count of B lymphocytes and expression of surface molecules CD23 and CD200 on B cells in AD patients and in control group. Non-parametric Kruskal-Wallis one-factor analysis of variance with post-hoc (follow-up multiple comparison) and Dunn's test with Bonferroni modification of significance level were used for statistical analysis. RESULTS: We confirmed the significantly higher number of neutrophils, monocytes and eosinophils and higher expression of CD23 and CD200 on B cells in peripheral blood of AD patients (either with or without dupilumab) therapy. We demonstrated the lower number of CD8+ T cells. CONCLUSION: We demonstrated the difference in the count of white blood cells populations in patients suffering from AD compared with healthy control. There were a differences in the expression of immunoregulatory molecules CD23 and CD200 on B cells in AD patients (either with or without dupilumab therapy) in comparison to healthy controls.
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Dermatite Atópica , Masculino , Humanos , Feminino , Adulto , Dermatite Atópica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Monócitos , Linfócitos B , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease that secondarily leads to axonal loss and associated brain atrophy. Disease-modifying drugs (DMDs) have previously been studied for their ability to affect specific immunity. This study investigates the effect of interferon beta-1a (INF) and glatiramer acetate (GA) administration on changes in innate immunity cell populations. METHODS: Sixty Caucasian female patients with relapsing-remitting MS undergo blood sample testing for 15 blood parameters at baseline, 1 month, 3 months, and 6 months after treatment by GA or IFN (started as their first-line DMD). RESULTS: A statistically significant difference in the change after 6 months was found in the parameter monocytes (relative count) in the group of patients treated with IFN. The median increase was 27.8%. Changes in many of the other 15 parameters studied were 10-20%. CONCLUSION: Innate immunity has long been neglected in MS immunopathology. The findings suggest that IFN treatment may modulate the immune response in MS by affecting monocyte function and may provide insight into the mechanisms of action of IFN in MS.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Feminino , Humanos , Acetato de Glatiramer/uso terapêutico , Interferon beta-1a/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Interferon beta/uso terapêutico , Peptídeos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Imunidade InataRESUMO
BACKGROUND: The CD23 molecule has an effect on the regulation of IgE synthesis, either by stimulation or inhibition. It is not yet known whether the expression of CD23 on B lymphocytes is related to the level of allergen-specific IgE antibodies in patients with atopic dermatitis. AIM: The aim of this pilot study was to evaluate the association between the expression of CD23 molecule on B cells and on their subsets (memory, naive, switched, non-switched, and total B lymphocytes) and the level of specific IgE to molecular components of mites in atopic dermatitis patients (with and without dupilumab therapy). METHODS: Forty-five patients suffering from atopic dermatitis were included: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years) and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). The serum level of the specific IgE was measured using the components resolved diagnostic microarray-based specific IgE detection assay ALEX2 Allergy Xplorer. In all included patients, the expression of CD23 molecule on B lymphocytes was evaluated with flow cytometry using monoclonal antibodies. For the statistical analysis of the association between expression of CD23 molecule on B lymphocytes and the level of specific IgE to molecular components of mites, we used non-parametric Kruskal-Wallis one-factor analysis of variance with post-hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (%, percent of Variation Explained). RESULTS: The association between the expression of CD23 molecule on B cells and the level of specific IgE to molecular components of mites was confirmed only in patients with dupilumab therapy. In these patients, the highest association was confirmed between the level of specific IgE to Der p 20 and expression of CD23 on switched B lymphocytes (in 48.9%). In patients without dupilumab, the association between the level of specific IgE to molecular components of mites and the expression of CD23 on B cells and on their subsets is low. CONCLUSION: Further research is needed to fully understand the underlying mechanism of this phenomenon and its implications for the treatment of atopic dermatitis.
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BACKGROUND: Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins. METHODS: We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes. RESULTS: FasL was increased in patients' T and B cells while Fas was increased in patients' monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients' serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren's syndrome. CONCLUSIONS: Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren's syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.
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Doenças Autoimunes , Síndrome de Sjogren , Humanos , Anexina A5 , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Apoptose , Receptor fas/metabolismoRESUMO
BACKGROUND: Eosinophils, basophils, and the molecule CD23 on B cells are involved in the pathophysiology of atopic dermatitis (AD). The molecule CD23 is involved in the regulation of IgE synthesis and is expressed by activated B cells. The molecule CD16 is used to assess the activation of eosinophils and CD203 of basophils. The association between the count of eosinophils, basophils, CD16+ eosinophils, CD203+ basophils and the expression of the activation marker CD23 on B cells in patients with AD (with and without dupilumab therapy) is not described. OBJECTIVE: The aim of this pilot study is to evaluate the association between the blood count of eosinophils, basophils, relative CD16+ eosinophils, relative CD203+ basophils, and the expression of molecule CD23 on B cells and on their subsets (total, memory, naive, switched, non-switched) in patients suffering from AD (with and without dupilumab therapy) and in control group. METHODS: A total of 45 patients suffering from AD were examined; 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. For statistical analysis we used non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (percent of variation explained). RESULTS: The absolute count of eosinophils was significantly higher in patients with AD (with and without dupilumab) in comparison to healthy subjects. The difference in the relative count of CD16+ eosinophils in patients with AD (with and without dupilumab therapy) compared with control is not statistically significant. In patients with dupilumab therapy the significantly lower count of relative CD203+ basophils was confirmed compared with control. The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with dupilumab therapy; in contrast, this association was low in patients with AD without dupilumab therapy and in healthy subjects. CONCLUSION: The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with AD under dupilumab therapy. It suggests that IL-4 production by eosinophils may play a role in B lymphocyte activation. The significantly lower count of CD203+ basophils has been demonstrated in patients with dupilumab therapy. This reduction of CD203+ basophil count may contribute to the therapeutic effects of dupilumab by reducing the inflammatory response and allergic reactions in patients with AD.
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Background: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function. Methods: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml. Results: The results showed that controls had nearly 2-fold higher levels of IFN-γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores. Conclusions: Results showed that controls had higher levels of IFN-γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN-γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Cloridrato de Fingolimode/uso terapêutico , Interferon gama , Ensaio de Imunoadsorção Enzimática , Sistema ImunitárioRESUMO
BACKGROUND: There are a lot of studies that describe the change in quantity of T cells in patients with atopic dermatitis (AD) compared with healthy subjects. Other components of lymphocytes such as B cells are not examined as well as T cells. OBJECTIVE: We focus on immunophenotyping of B cells with their subsets (memory, naïve, switched, non-switched) and the expression of CD23 and CD200 markers in patients with AD with and without dupilumab therapy. We also evaluate the count of leukocytes and their subsets, T lymphocytes (CD4+, CD8+), natural killer (NK) cells, and T regulatory cells. METHODS: A total of 45 patients suffering from AD were examined: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. We compared the absolute and relative count of leukocytes and their subsets, T lymphocytes (CD4+ , CD8+), NK cells, T regulatory cells, absolute and relative count of B lymphocytes (memory, naïve, non-switched, switched, transient), and expression of CD23 and CD200 activation markers on B cells and on their subsets in patients with AD and control group. For statistical analysis we used nonparametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification of significance level. RESULTS: In patients with AD with and without dupilumab therapy we confirmed the significantly higher count of neutrophils, monocytes, and eosinophils; there was no difference in absolute count of B cells, NK cells and transitional B cells compared with control subjects. We confirmed higher expression of activation marker CD23 on total, memory, naïve, non-switched, and switched B lymphocytes and higher expression of CD200 on total B lymphocytes in both groups of patients with AD compared with controls. In patients without dupilumab therapy we confirmed significantly higher count of relative monocytes, relative eosinophils, and higher expression of CD200 on memory, naïve, and non-switched B lymphocytes compared with controls. In patients with dupilumab therapy we confirmed significantly higher expression of CD200 on switched B lymphocytes, higher count of relative CD4+ T lymphocytes, and lower count of absolute CD8+ T lymphocytes compared with controls. CONCLUSION: This pilot study shows higher expression of CD23 on B lymphocytes and on their subsets in patients with AD with and without dupilumab therapy. The higher expression of CD200 on switched B lymphocytes is confirmed only in patients with AD with dupilumab therapy.
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Psoriasis and metabolic syndrome (MetS) are chronic inflammatory conditions associated with the dysregulation of immune system reactivity. The inflammatory processes of both diseases have not yet been fully characterized, and the evaluation of proteins/markers that could be involved in their pathogenesis is of great importance. We selected four markers: CRP, sCD200R1, CD5L, and sTLR2; in particular, sCDR2001 has not yet been measured in the context of psoriasis and metabolic syndrome. Material and methods: In the study, 64 controls and 43 patients with psoriasis with or without a metabolic syndrome were enrolled. The levels of selected markers were measured using ELISA kits. Results: CRP levels were significantly higher in psoriasis patients, especially in the subgroup of patients with MetS compared to nonMetS patients (p < 0.01). sCD200R1 and sTLR2 were not significantly different between groups and subgroups; however, CD200R1 levels were slightly higher in both control groups compared to both groups of patients. CD5L levels were significantly higher in patients with MetS compared to nonMets patients (p < 0.02). We also evaluated the correlations between parameters in controls and patients' groups, as well as in subgroups. Correlations between BMI and CRP were found in all groups and subgroups. Other correlations were group- and subgroup-specific. For example, in the patients' group, CD5L correlated with sCD200R1 (p < 0.05) and in MetS controls, with age (p < 0.03). Conclusion: The results show that the presence of systemic inflammation associated with psoriasis and metabolic syndrome and their combination alters the expression of specific molecules, especially CRP and CD5L, which were significantly increased in patients with psoriasis and a metabolic syndrome compared to controls without metabolic syndromes. Correlations between CRP and BMI in all groups suggest that overweight and obesity increase the intensity of inflammation and potentiate CD5L expression. In contrast, levels of molecules that may limit inflammation were not increased in psoriasis and metabolic syndrome subjects (they were non-significantly lower compared with healthy controls), which may reflect the chronic nature of both diseases and the exhaustion of inhibitory mechanisms.
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INTRODUCTION: Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency. METHODS: We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay). RESULTS: We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination. CONCLUSION: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.
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Vacinas contra COVID-19 , COVID-19 , Imunodeficiência de Variável Comum , Síndromes de Imunodeficiência , Humanos , Imunodeficiência de Variável Comum/terapia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Imunoglobulina A , Imunoglobulina G , RNA Mensageiro , SARS-CoV-2 , VacinaçãoRESUMO
In the field of science, technology and medicine, carbon-based nanomaterials and nanoparticles (CNMs) are becoming attractive nanomaterials that are increasingly used. However, it is important to acknowledge the risk of nanotoxicity that comes with the widespread use of CNMs. CNMs can enter the body via inhalation, ingestion, intravenously or by any other route, spread through the bloodstream and penetrate tissues where (in both compartments) they interact with components of the immune system. Like invading pathogens, CNMs can be recognized by large numbers of receptors that are present on the surface of innate immune cells, notably monocytes and macrophages. Depending on the physicochemical properties of CNMs, i.e., shape, size, or adsorbed contamination, phagocytes try to engulf and process CNMs, which might induce pro/anti-inflammatory response or lead to modulation and disruption of basic immune activity. This review focuses on existing data on the immunotoxic potential of CNMs, particularly in professional phagocytes, as they play a central role in processing and eliminating foreign particles. The results of immunotoxic studies are also described in the context of the entry routes, impacts of contamination and means of possible elimination. Mechanisms of proinflammatory effect depending on endocytosis and intracellular distribution of CNMs are highlighted as well.
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Carbono , Nanoestruturas , Carbono/química , Macrófagos , Nanoestruturas/química , Nanoestruturas/toxicidadeRESUMO
Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases of either infectious or non-infectious CNS involvement. Neutrophils are effector cells of innate immunity. Predominance of neutrophils was found in 98.2% of patients with purulent inflammation in CNS. Lymphocytes are cellular substrate of adaptive immunity. We found their predominance in 94.8% of patients with multiple sclerosis (MS), 66.7% of patients with tick-borne encephalitis (TBE), 92.2% of patients with neuroborreliosis, 83.3% of patients with inflammatory response with oxidative burst of macrophages in CNS and 75.0% of patients with malignant infiltration of meninges (MIM). The simultaneous assessment of aerobic and anaerobic metabolism in CSF using the coefficient of energy balance (KEB) allows us to specify the type of inflammation in CNS. We found predominantly aerobic metabolism (KEB > 28.0) in 100.0% CSF of patients with normal CSF findings and in 92.8% CSF of patients with MS. Predominant faintly anaerobic metabolism (28.0 > KEB > 20.0) in CSF was found in 71.8% patients with TBE and in 64.7% patients with neuroborreliosis. Strong anaerobic metabolism (KEB < 10.0) was found in the CSF of 99.1% patients with purulent inflammation, 100.0% patients with inflammatory response with oxidative burst of macrophages and in 80.6% patients with MIM. Joint evaluation of basic CSF parameters provides sufficient information about the immune response in the CSF compartment for rapid and reliable diagnosis of CNS involvement.