Chronic spontaneous urticaria: Evidence of systemic microcirculatory changes.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a chronic inflammatory skin disease where activation of endothelial cells (ECs) at sites of skin lesions leads to increased blood flow, leakage of fluid into the skin, cellular infiltration, and vascular remodeling. To understand the disease duration and the sometimes vague systemic symptoms accompanying flares, the objective of this study was to examine if CSU comes with systemic vascular changes at the microcirculatory level. METHODS: We investigated CSU patients (n = 49) and healthy controls (HCs, n = 44) for microcirculatory differences by nailfold videocapillaroscopy (NVC) and for blood levels of the soluble EC biomarkers serum vascular endothelial growth factor (VEGF), soluble E-selectin, and stem cell factor (SCF). Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). RESULTS: CSU patients had significantly lower capillary density, more capillary malformations, and more irregular capillary dilations than HCs on NVC. Serum levels of VEGF, soluble E selectin and SCF were similar in CSU patients and HCs. CSU patients with higher VEGF levels had significantly more abnormal capillaries. Patients with markers of aiCSU, that is, low IgE levels or increased anti-TPO levels, had significantly more capillaries and less capillary dilations than those without. CONCLUSION: Our results suggest that CSU comes with systemic microcirculatory changes, which may be driven, in part, by VEGF.

Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department.

BACKGROUND: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. METHODS: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. RESULTS: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. CONCLUSION: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.

Sex-biased expression of selected chromosome x-linked microRNAs with potent regulatory effect on the inflammatory response in children with cystic fibrosis: A preliminary pilot investigation.

Previous studies have reported sex disparity in cystic fibrosis (CF) disease, with females experiencing more pulmonary exacerbations and frequent microbial infections resulting in shorter survival expectancy. This concerns both pubertal and prepubertal females, which is in support to the prominent role of gene dosage rather than the hormonal status. The underlying mechanisms are still poorly understood. The X chromosome codes for a large number of micro-RNAs (miRNAs) that play a crucial role in the post-transcriptional regulation of several genes involved in various biological processes, including inflammation. However, their level of expression in CF males and females has not been sufficiently explored. In this study, we compared in male and female CF patients the expression of selected X-linked miRNAs involved in inflammatory processes. Cytokine and chemokine profiles were also evaluated at both protein and transcript levels and cross-analyzed with the miRNA expression levels. We observed increased expression of miR-223-3p, miR-106a-5p, miR-221-3p and miR-502-5p in CF patients compared to healthy controls. Interestingly, the overexpression of miR-221-3p was found to be significantly higher in CF girls than in CF boys and this correlates positively with IL-1ß. Moreover, we found a trend toward lower expression in CF girls than in CF boys of suppressor of cytokine signaling 1 (SOCS1) and the ubiquitin-editing enzyme PDLIM2, two mRNA targets of miR-221-3p that are known to inhibit the NF-κB pathway. Collectively, this clinical study highlights a sex-bias in X-linked miR-221-3p expression in blood cells and its potential contribution to sustaining a higher inflammatory response in CF girls.

Pilot study on the use of basophil activation tests and skin tests for the prevention of allergic transfusion reactions.

Background and objectives: Management of severe allergic transfusion reactions (ATR) is challenging. In this study, we investigate the usefulness of skin tests and basophil activation tests (BAT) in chronically transfused patients for the prevention of future ATR. Materials and methods: BAT and skin tests were carried with the supernatant of red blood cell (RBC) units for a sickle-cell disease patient under chronic exchange transfusion who has presented a severe ATR, in order to prevent potential future ATR. If the results for both BAT and skin tests were negative, the RBC units could be transfused to the patient. If either one of the results was positive, the tested RBC unit was discarded for the patient. Results: 192 RBC units were tested with both tests. The level of results concordance between the two tests was 95%. Out of the 169 negative units with both tests, 118 units were transfused to the patient for which he presented no ATR. Conclusion: In our study, combining both BAT and skin tests was associated with a good negative predictive value since we were able to safely transfuse our patient. Further studies are still necessary to confirm this result but this pilot study indicates that skin tests and BAT might help prevent ATR. When BAT is not available, skin tests may also be useful in preventing ATR.

Novel role of UHRF1 in the epigenetic repression of the latent HIV-1.

BACKGROUND: The multiplicity, heterogeneity, and dynamic nature of human immunodeficiency virus type-1 (HIV-1) latency mechanisms are reflected in the current lack of functional cure for HIV-1. Accordingly, all classes of latency-reversing agents (LRAs) have been reported to present variable ex vivo potencies. Here, we investigated the molecular mechanisms underlying the potency variability of one LRA: the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC). METHODS: We employed epigenetic interrogation methods (electrophoretic mobility shift assays, chromatin immunoprecipitation, Infinium array) in complementary HIV-1 infection models (latently-infected T-cell line models, primary CD4+ T-cell models and ex vivo cultures of PBMCs from HIV+ individuals). Extracellular staining of cell surface receptors and intracellular metabolic activity were measured in drug-treated cells. HIV-1 expression in reactivation studies was explored by combining the measures of capsid p24Gag protein, green fluorescence protein signal, intracellular and extracellular viral RNA and viral DNA. FINDINGS: We uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) to the HIV-1 promoter. We showed that UHRF1 redundantly binds to the HIV-1 promoter with different binding modalities where DNA methylation was either non-essential, essential or enhancing UHRF1 binding. We further demonstrated the role of UHRF1 in the epigenetic repression of the latent viral promoter by a concerted control of DNA and histone methylations. INTERPRETATION: A better understanding of the molecular mechanisms of HIV-1 latency allows for the development of innovative antiviral strategies. As a proof-of-concept, we showed that pharmacological inhibition of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent viral reactivation from latency. Together, we identify UHRF1 as a novel actor in HIV-1 epigenetic silencing and highlight that it constitutes a new molecular target for HIV-1 cure strategies. FUNDING: Funding was provided by the Belgian National Fund for Scientific Research (F.R.S.-FNRS, Belgium), the « Fondation Roi Baudouin ¼, the NEAT (European AIDS Treatment Network) program, the Internationale Brachet Stiftung, ViiV Healthcare, the Télévie, the Walloon Region (« Fonds de Maturation ¼), « Les Amis des Instituts Pasteur à Bruxelles, asbl ¼, the University of Brussels (Action de Recherche Concertée ULB grant), the Marie Skodowska Curie COFUND action, the European Union's Horizon 2020 research and innovation program under grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015, the French Agency for Research on AIDS and Viral Hepatitis (ANRS), the Sidaction and the "Alsace contre le Cancer" Foundation. This work is supported by 1UM1AI164562-01, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases.

Durability of tetanus seroprotection in people living with HIV.

OBJECTIVES: The aim of this study was to estimate the durability of tetanus toxoid specific seroprotection in a cohort of people with HIV (PWH). DESIGN: A cross-sectional study. METHODS: PWH with a last date of tetanus toxoid booster available were identified. Tetanus toxoid specific IgG were detected using commercial ELISA kit. Durability of seroprotection was estimated using a linear regression model and analyzed according to the country of birth. The impact of baseline parameters at the time of vaccination (CD4 + T cell count, viral load, and antiretroviral therapy) was also assessed. RESULTS: One hundred three individuals were included. The median duration between last tetanus toxoid booster and sampling was 5.6years (IQR 2.6-8.9). Using a linear regression model, half-life of tetanus toxoid specific antibody was estimated at 9.9 years [95% confidence interval (95% CI: 5.5-50)] in the whole cohort. Half-life was reduced in individuals born outside Europe: 4.4 years (95% CI: 2.9-8.5). PWH born outside Europe had lower CD4 + T cell count at the time of immunization and more frequently a CD4 + T cell count nadir less than 200 cells/µl before vaccination. CONCLUSION: PWH born outside Europe have lower half-life of tetanus toxoid specific antibody as compared to previous study performed in the general population. Possible causes include lower nadir or current CD4 + T cell count or under-immunization status in country of origin before migration. Longer interval of booster vaccination, as recommended in the general population, might not be appropriate in this subgroup of PWH. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Tocilizumab-Induced Unexpected Increase of Several Inflammatory Cytokines in Critically Ill COVID-19 Patients: The Anti-Inflammatory Side of IL-6.

Early evidence during the coronavirus disease 2019 (COVID-19) pandemic indicated high levels of interleukin (IL)-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic. While the monoclonal antibody blocks IL-6 pathway, its effect on other inflammatory cytokines remains poorly described. To better understand the effect of TCZ on the biological inflammatory profile, we monitored a large panel of inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Twenty-three patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the study, among which 15 patients received TCZ and 8 patients did not. Serum samples were collected for 8 days, before and following TCZ administration or hospital admission for the control group. Serum profile of 12 cytokines (IL-1ß, -2, -4, -6, -8, -10, -12, -13, -17, -18, tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), and sIL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1ß, -2, -4, -10, -12p70, -18, and sIL-6R levels in the treated patients with maximal values reaching 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. Our results suggested that some inflammatory pathways escape IL-6R blockade and even appeared amplified. This finding highlights an old observation of the anti-inflammatory effects of IL-6 as already suggested over 20 years ago. Clinical Trial Registration number: NCT04346017.

Helminth infection induces non-functional sensitization to house dust mites.

BACKGROUND: IgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE. OBJECTIVE: To study the IgE response against environmental allergens induced during natural helminth infection. METHODS: In 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt. RESULTS: Non allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different. CONCLUSION: Helminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as ß-1,2-xylose and/or ⍺-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.

Hookworm treatment induces a decrease of suppressive regulatory T cell associated with a Th2 inflammatory response.

BACKGROUND: Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment. METHODOLOGY: Twenty hookworm infected (HW+) and 14 non-infected subjects HW-from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1ß, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFß. RESULTS: HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased. CONCLUSION: During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.

Discrimination of COVID-19 From Inflammation-Induced Cytokine Storm Syndromes Using Disease-Related Blood Biomarkers.

OBJECTIVE: Infection with the novel coronavirus SARS-CoV-2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID-19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID-19 are still lacking. The aim of this study was to directly address whether immune activation in COVID-19 does indeed mimic the conditions found in these classic cytokine storm syndromes. METHODS: Levels of 22 biomarkers were quantified in serum samples from patients with COVID-19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single-marker enzyme-linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome. RESULTS: In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin-18 (IL-18)-interferon-γ axis, increased serum levels of IL-1 receptor antagonist, intercellular adhesion molecule 1, and IL-8, and strongly reduced levels of soluble Fas ligand in the course of SARS-CoV-2 infection. These observations appeared to discriminate immune dysregulation in critical COVID-19 from the well-recognized characteristics of other cytokine storm syndromes. CONCLUSION: Serum biomarker profiles clearly separate COVID-19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS-CoV-2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID-19.

Tetanus seroprotection in people living with HIV: Risk factors for seronegativity, evaluation of medical history and a rapid dipstick test.

OBJECTIVES: Tetanus is a vaccine-preventable disease. Booster immunization is required in order to induce long-lived tetanus-toxoid (TT) specific antibody response. We investigated the prevalence and risk factors of TT seronegativity in a cohort of people living with HIV (PWH) in Belgium along with the respective performance of vaccine history and a rapid dipstick test (Tetanus Quick Stick ® or TQS) compared to ELISA testing. METHODS: PWH were prospectively enrolled and answered a questionnaire. ELISA was performed on serum or plasma using a commercial kit. A TT antibody level ≥ 0.15 IU / mL was considered protective. The TQS test was performed on a limited number of subjects. RESULTS: Three-hundred forty-four subjects were included. The prevalence of tetanus seroprotection was 84,9%. Median age was 46.7 and 68% were born outside Belgium. Antiretroviral therapy coverage was almost universal (98.5%). After multivariable analysis, two risk factors were independently associated with TT seronegativity: an education level equivalent or below than secondary school and being born outside Europe. Vaccine history was shown to be unreliable (sensitivity: 43.8%; specificity: 76.5%; positive predictive value: 91.4% and negative predictive value :19.3%). The correlation between vaccine history and tetanus seroprotection was low (kappa coefficient = 0.09). The TQS performances were good (sensitivity 86.4%, specificity 96.0%, positive predictive value 99.3%, negative predictive value 52.17%). The correlation between TQS and tetanus seroprotection was substantial (kappa coefficient = 0.61). CONCLUSIONS: In this cohort of PWH with a high proportion of migrants, socio-demographic and educational factors were associated with TT seronegativity while HIV-related factors were not, indicating that vaccine information should be tailored to cultural and educational background. As vaccine history is not reliable, TQS could represent an efficient tool for screening of TT-seronegativity.

Biomarkers for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

Many biomarkers have been proposed for the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) in adults, but comparative studies are lacking. We analyzed ferritin, glycosylated ferritin, soluble CD25, CD163 and CD14, IL-6, IFN-γ, IL-18, IL-10, IL-1ß, IL-12p70, IL-17α, IP-10, and CXCL9 levels to differentiate HLH from sepsis in critically ill patients. Of 120 patients, HLH was confirmed for 14 patients. Among the biomarkers tested, ferritin, IL-18, and glycosylated ferritin were the most efficient parameters for early diagnosis of HLH. With a sensitivity set at 85%, ferritin, IL-18, and glycosylated ferritin were the biomarkers with the highest specificity: 84, 79, and 71% respectively. Combining IL-18 with the HScore provided a new score with an increased specificity compared to the HScore alone, 86% compared to 70% with a sensitivity set at 100%. A distinct cytokine pattern was highlighted in patients with malignancy-triggered HLH, with highly increased levels of INF-É£ and CXCL9, compared to HLH secondary to infection. This is the largest study available to date, comparing diagnostic biomarkers for HLH on a cohort of critically ill adult patients. Serum ferritin was the most discriminating parameter for early diagnosis of secondary HLH. IL18*HScore was identified as a highly potential score.

Covid-19 and blood groups: ABO antibody levels may also matter.

BACKGROUND: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. METHODS: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. RESULTS: We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. CONCLUSION: In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. METHODS: We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. RESULTS: Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). CONCLUSIONS: Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.

A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer.

OBJECTIVES: We aimed to explore cytokine profile in patients as it relates to Coronavirus Disease 2019 (COVID-19) severity, and to establish a predictive cytokine score to discriminate severe from non-severe cases and provide a prognosis parameter for patients that will require intensive care unit (ICU) transfer. METHODS: Serum samples of 63 patients diagnosed with SARS-CoV-2 infection were collected early after hospital admission (day 0-3). Patients were categorized in five groups based on the clinical presentation, the PaO2/FiO2 ratio and the requirement of mechanical ventilation. RESULTS: Three cytokines, IL-6, IL-8 and IL-10, were markedly higher in severe forms (n = 44) than in non-severe forms (n = 19) (p < 0.005). A score combining levels of these three cytokines (IL-6*IL-8*IL-10) had the highest performance to predict severity: sensitivity of 86.4% (95% CI, 72.4-94.8) and specificity of 94.7% (95% CI, 74.0-99.9) for a cutoff value of 2068 pg/mL. Elevated levels of IL-6, IL-8 and IL-10 were also found in critically ill patients. The combination of IL-6*IL-10 serum levels allowed the highest predictability for ICU transfer: AUC of 0.898 (p < 0.0001). CONCLUSION: The combinatorial IL-6*IL-8*IL-10 score at presentation was highly predictive of the progression to a severe form of the disease, and could contribute to improve patient triage and to adapt therapeutic strategy within clinical trials more accurately and efficiently.

Hyperoxia Alters Ultrastructure and Induces Apoptosis in Leukemia Cell Lines.

Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decrease in cancer cell proliferation occurring after exposure to normobaric hyperoxia. Those changes are associated with fractal dimension. The purpose of this research was to study the impact of hyperoxia on apoptosis and morphology of leukemia cell lines. Two hematopoietic lymphoid cancer cell lines (a T-lymphoblastoid line, JURKAT and a B lymphoid line, CCRF-SB) were tested under conditions of normobaric hyperoxia (FiO2 > 60%, ± 18h) and compared to a standard group (FiO2 = 21%). We tested for apoptosis using a caspase-3 assay. Cell morphology was evaluated by cytospin, microphotography after coloration, and analysis by a fractal dimension calculation software. Our results showed that exposure of cell cultures to transient normobaric hyperoxia induced apoptosis (elevated caspase-3) as well as significant and precocious modifications in cell complexity, as highlighted by increased fractal dimensions in both cell lines. These features are associated with changes in structure (pycnotic nucleus and apoptosis) recorded by microscopic analysis. Such morphological alterations could be due to several molecular mechanisms and rearrangements in the cancer cell, leading to cell cycle inhibition and apoptosis as shown by caspase-3 activity. T cells seem less resistant to hyperoxia than B cells.

The protective effect of rural life on mite sensitization disappears among urban migrants in the South of Vietnam.

BACKGROUND: Rapid urbanization combined with rural migration to urban areas in southern Vietnam could be risk factors for allergen sensitization, contributing to chronic respiratory diseases (CRD). We aimed to evaluate the prevalence of mite sensitization and its relation to house dust characteristics among rural and urban native and migrating populations with CRD. METHODS: Rural (n = 19) and urban (n = 46) dwellings were defined on the basis of a home typology. Controls were western Belgian houses (n = 14). Besides the house characteristics, both endotoxin and mite allergens were measured in the settled dusts. The sensitization to mite allergens was defined by positive skin prick test (SPT) and concentration of specific IgE (sIgE)≥ 0.7 U/mL. The prevalence of mite sensitization was evaluated among 610 patients with CRD and compared according to both their home types and places of birth and residences. RESULTS: The concentration of endotoxin (but not mite allergen) was higher in rural compared to urban dusts (440 (95%CI: 314-566) versus 170 (95%CI: 115-226) EU/mg; p < 0.0001). The prevalence of positive sIgE to Der p1 and Der p2 was significantly lower in rural (9% and 5%) compared to urban (15% and 9%) population, consistent with the positive SPT to mite (14% and 21%, respectively). Among the urban migrants, the risk of mite sensitization (SPT) was higher compared to the rural natives (OR: 1.79 (1.02-3.15), p < 0.05) and not different to the urban ones (OR: 1.35 (0.82-2.23) p NS). CONCLUSION: In Vietnam, associated with higher endotoxin (but not allergen) dust concentrations, the risk of mite sensitization was lower in rural compared to the native urban population, but this protective effect could disappear among rural to urban migrants.

Alteration of humoral, cellular and cytokine immune response to inactivated influenza vaccine in patients with Sickle Cell Disease.

INTRODUCTION: Patients suffering from Sickle Cell Disease (SCD) are at increased risk for complications due to influenza virus. Annual influenza vaccination is strongly recommended but few clinical studies have assessed its immunogenicity in individuals with SCD. The aim of this study was to explore the biological efficacy of annual influenza vaccination in SCD patients by characterizing both their humoral and cell-mediated immunity against influenza antigen. We also aimed to investigate these immunological responses among SCD individuals according to their treatment (hydroxyurea (HU), chronic blood transfusions (CT), both HU and CT or none of them). METHODS: Seventy-two SCD patients (49 receiving HU, 9 on CT, 7 with both and 7 without treatment) and 30 healthy controls were included in the study. All subjects received the tetravalent influenza α-RIX-Tetra® vaccine from the 2016-2017 or 2017-2018 season. RESULTS: Protective anti-influenza HAI titers were obtained for the majority of SCD patients one month after vaccination but seroconversion rates in patient groups were strongly decreased compared to controls. Immune cell counts, particularly cellular memory including memory T and memory B cells, were greatly reduced in SCD individuals. Functional activation assays confirmed a poorer CD8+ T cell memory. We also document an imbalance of cytokines after influenza vaccination in SCD individuals with an INFγ/IL-10 ratio (Th1-type/Treg-type response) significantly lower in the SCD cohort. CONCLUSION: SCD patients undergoing CT showed altered immune regulation as compared to other treatment subgroups. Altogether, the cytokine imbalance, the high regulatory T cell levels and the low memory lymphocyte subset levels observed in the SCD cohort, namely for those on CT, suggest a poor ability of SCD patients to fight against influenza infection. Nevertheless, our serological data support current clinical practice for annual influenza vaccination, though immunogenicity to other vaccines involving immunological memory might be hampered in SCD patients and should be further investigated.