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1.
Virol J ; 21(1): 143, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915037

ABSTRACT

BACKGROUND: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections. METHODS: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves. RESULTS: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers. CONCLUSIONS: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.


Subject(s)
Asymptomatic Infections , COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/blood , COVID-19/virology , Male , Female , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Middle Aged , Adult , Aged , Young Adult , Severity of Illness Index , Neutrophils/immunology , C-Reactive Protein/analysis , Biomarkers/blood , Basophils , ROC Curve , Adolescent
2.
Front Immunol ; 15: 1379833, 2024.
Article in English | MEDLINE | ID: mdl-38911871

ABSTRACT

Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.


Subject(s)
Allergens , Cross Reactions , Immunoglobulin E , Pollen , Profilins , Salsola , Humans , Profilins/immunology , Profilins/chemistry , Immunoglobulin E/immunology , Allergens/immunology , Allergens/genetics , Salsola/immunology , Female , Pollen/immunology , Male , Cross Reactions/immunology , Adult , Recombinant Proteins/immunology , Rhinitis, Allergic, Seasonal/immunology , Middle Aged , Basophils/immunology , Basophils/metabolism , Antigens, Plant/immunology , Antigens, Plant/genetics , Young Adult , Adolescent , Plant Proteins/immunology , Plant Proteins/genetics
3.
Trop Biomed ; 41(1): 118-124, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38852141

ABSTRACT

Dengue is a mosquito-transmitted infection endemic in tropical and subtropical locations of the world where nearly half of the world's population resides. The disease may present as mild febrile illness to severe and can even be fatal if untreated. There are four genetically related but antigenically distinct dengue virus (DENV) serotypes. Immune responses to DENV infection are in general protective but under certain conditions, they can also aggravate the disease. The importance of the cellular immune responses and the antibody responses involving IgG and IgM has been well-studied. In contrast, not much has been described on the potential role of hypersensitivity reactions involving IgE in dengue. Several studies have shown elevated levels of IgE in patients with dengue fever, but its involvement in the immune response against the virus and disease is unknown. Activation of mast cells (MCs) and basophils mediated through dengue-specific IgE could result in the release of mediators affecting dengue virus infection. The present review explores the relationships between the induction of IgE in dengue virus infection, and the potential role of MCs and basophils, exploring both protective and pathogenic aspects, including antibody-dependent enhancement (ADE) of infection in dengue.


Subject(s)
Dengue Virus , Dengue , Immunoglobulin E , Dengue/immunology , Humans , Immunoglobulin E/immunology , Dengue Virus/immunology , Mast Cells/immunology , Animals , Antibody-Dependent Enhancement , Basophils/immunology , Antibodies, Viral
4.
Pediatr Allergy Immunol ; 35(6): e14140, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38822743

ABSTRACT

Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.


Subject(s)
Peanut Hypersensitivity , Sensitivity and Specificity , Peanut Hypersensitivity/diagnosis , Peanut Hypersensitivity/immunology , Humans , Basophils/immunology , Arachis/immunology , Child , Mast Cells/immunology , Basophil Degranulation Test/methods , Allergens/immunology , Adult
5.
Front Immunol ; 15: 1343024, 2024.
Article in English | MEDLINE | ID: mdl-38784378

ABSTRACT

Background: Around 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation. Methods: Nanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients' IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated. Results: Trimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release. Conclusion: We generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.


Subject(s)
Allergens , Antigens, Plant , Cross Reactions , Immunoglobulin E , Single-Domain Antibodies , Immunoglobulin E/immunology , Immunoglobulin E/metabolism , Humans , Antigens, Plant/immunology , Single-Domain Antibodies/immunology , Cross Reactions/immunology , Allergens/immunology , Basophils/immunology , Basophils/metabolism , Protein Binding , Rhinitis, Allergic, Seasonal/immunology , Protein Multimerization
6.
PLoS Negl Trop Dis ; 18(5): e0012203, 2024 May.
Article in English | MEDLINE | ID: mdl-38771861

ABSTRACT

BACKGROUND: Chronic infection by Loa loa remains an unsolved immunological paradox. Despite harboring subcutaneously migrating adult worms and often high densities of microfilariae, most patients experience only relatively mild symptoms, yet microfilaricidal treatment can trigger life-threatening inflammation. Here, we investigated innate cell populations hypothesized to play a role in these two faces of the disease, in an endemic population in Gabon. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed numbers and activation of eosinophils and basophils, as well as myeloid-derived suppressor cell (MDSC) subsets and associated circulating cytokine levels by flow cytometry in sex- and age-matched L. loa-uninfected (LL-), -amicrofilaraemic (MF-) and -microfilaraemic (MF+) individuals (n = 42), as well as microfilaraemic individuals treated with albendazole (n = 26). The percentage of eosinophils was lower in LL- (3.0%) than in the combined L. loa-infected population, but was similar in MF+ (13.1%) and MF- (12.3%). Upon treatment of MF+, eosinophilia increased from day 0 (17.2%) to day 14 (24.8%) and had decreased below baseline at day 168 (6.3%). Expression of the eosinophil activation marker CD123 followed the same pattern as the percentage of eosinophils, while the inverse was observed for CD193 and to some extent CD125. Circulating IL-5 levels after treatment followed the same pattern as eosinophil dynamics. Basophil numbers did not differ between infection states but increased after treatment of MF+. We did not observe differences in MDSC numbers between infection states or upon treatment. CONCLUSIONS/SIGNIFICANCE: We demonstrate that both chronic infection and treatment of L. loa microfilaraemia are associated with eosinophil circulation and distinct phenotypical activation markers that might contribute to inflammatory pathways in this setting. In this first ever investigation into MDSC in L. loa infection, we found no evidence for their increased presence in chronic loiasis, suggesting that immunomodulation by L. loa is induced through other pathways.


Subject(s)
Basophils , Eosinophils , Loa , Loiasis , Myeloid-Derived Suppressor Cells , Humans , Loiasis/drug therapy , Loiasis/immunology , Male , Female , Adult , Eosinophils/immunology , Gabon/epidemiology , Basophils/immunology , Loa/physiology , Loa/immunology , Animals , Middle Aged , Myeloid-Derived Suppressor Cells/immunology , Young Adult , Albendazole/therapeutic use , Chronic Disease , Flow Cytometry , Cytokines , Endemic Diseases , Adolescent
7.
Immunohorizons ; 8(5): 371-383, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38780542

ABSTRACT

Our previous work demonstrated that basophils regulate a suite of malaria phenotypes, including intestinal mastocytosis and permeability, the immune response to infection, gametocytemia, and parasite transmission to the malaria mosquito Anopheles stephensi. Given that activated basophils are primary sources of the regulatory cytokines IL-4 and IL-13, we sought to examine the contributions of these mediators to basophil-dependent phenotypes in malaria. We generated mice with basophils depleted for IL-4 and IL-13 (baso IL-4/IL-13 (-)) and genotype controls (baso IL-4/IL-13 (+)) by crossing mcpt8-Cre and Il4/Il13fl/fl mice and infected them with Plasmodium yoelii yoelii 17XNL. Conditional deletion was associated with ileal mastocytosis and mast cell (MC) activation, increased intestinal permeability, and increased bacterial 16S levels in blood, but it had no effect on neutrophil activation, parasitemia, or transmission to A. stephensi. Increased intestinal permeability in baso IL-4/IL-13 (-) mice was correlated with elevated plasma eotaxin (CCL11), a potent eosinophil chemoattractant, and increased ileal MCs, proinflammatory IL-17A, and the chemokines MIP-1α (CCL3) and MIP-1ß (CCL4). Blood bacterial 16S copies were positively but weakly correlated with plasma proinflammatory cytokines IFN-γ and IL-12p40, suggesting that baso IL-4/IL-13 (-) mice failed to control bacterial translocation into the blood during malaria infection. These observations suggest that basophil-derived IL-4 and IL-13 do not contribute to basophil-dependent regulation of parasite transmission, but these cytokines do orchestrate protection of intestinal barrier integrity after P. yoelii infection. Specifically, basophil-dependent IL-4/IL-13 control MC activation and prevent infection-induced intestinal barrier damage and bacteremia, perhaps via regulation of eosinophils, macrophages, and Th17-mediated inflammation.


Subject(s)
Bacterial Translocation , Basophils , Interleukin-13 , Interleukin-4 , Malaria , Plasmodium yoelii , Animals , Interleukin-13/metabolism , Basophils/immunology , Basophils/metabolism , Malaria/immunology , Mice , Plasmodium yoelii/immunology , Interleukin-4/metabolism , Mast Cells/immunology , Mast Cells/metabolism , Mice, Inbred C57BL , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/parasitology , Mice, Knockout , Female , Anopheles/parasitology , Anopheles/immunology , Anopheles/microbiology
8.
Immun Inflamm Dis ; 12(5): e1265, 2024 May.
Article in English | MEDLINE | ID: mdl-38722265

ABSTRACT

BACKGROUND: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges. METHODS: We enrolled 34 patients aged 5-15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined. RESULTS: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p < .001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p < .001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p = .041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = -0.418, p = .027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders. CONCLUSION: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.


Subject(s)
Allergens , Basophils , Caseins , Immunoglobulin E , Milk Hypersensitivity , Humans , Basophils/immunology , Basophils/metabolism , Caseins/immunology , Milk Hypersensitivity/immunology , Milk Hypersensitivity/diagnosis , Milk Hypersensitivity/blood , Immunoglobulin E/immunology , Immunoglobulin E/blood , Female , Male , Child , Adolescent , Child, Preschool , Allergens/immunology , Animals , Milk/immunology , Milk/adverse effects , Double-Blind Method
9.
Anat Histol Embryol ; 53(3): e13054, 2024 May.
Article in English | MEDLINE | ID: mdl-38735037

ABSTRACT

Identifying and analysing distinct blood cells is crucial for the diagnosis and treatment of diseases in the field of biomedicine. The present study was undertaken to study the cytomorphological and cytochemical characteristics of the blood cells of Zoar, a non-descript indigenous breed of chicken extensively reared under backyard poultry farming in Mizoram, India. For this study, 2 mL of blood samples were aseptically collected from the wings veins of 12 chickens and were processed for light microscopic study under standard protocols. The matured erythrocytes were elliptical, while the immature erythrocytes appeared oval. The heterophils were positive for SBB (SBB), Periodic Acid Schiff (PAS), acid phosphatase, alkaline phosphatase and Arylsulphatase while the eosinophils were positive for SBB, PAS, alkaline phosphatase, cytochrome oxidase and peroxidase. The basophils of were positive for toluidine blue while the thrombocytes were positive for PAS. These cytochemical and cytoenzymatic staining properties plays a very important role in diagnosis, differentiation, and classification of leukaemias.


Subject(s)
Chickens , Eosinophils , Erythrocytes , Animals , Chickens/anatomy & histology , India , Erythrocytes/cytology , Eosinophils/cytology , Blood Cells/cytology , Blood Platelets/cytology , Alkaline Phosphatase/blood , Basophils/cytology , Acid Phosphatase/blood , Electron Transport Complex IV/analysis
10.
Clin Exp Allergy ; 54(6): 378-387, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38686464

ABSTRACT

In the past two decades, we witnessed the evolution of the basophil activation test (BAT) from mainly research applications to a potential complementary diagnostic tool to document IgE-dependent allergies. However, BAT presents some technical weaknesses. Around 10%-15% of tested patients are non-responders, BAT can be negative immediately post-reaction and the use of fresh basophils, ideally analysed within 4 h of collection, restricts the number of tests that can be performed per sample. The need for fresh basophils is especially limiting when conducting batch analyses and interlaboratory comparisons to harmonize BAT methodology. These limitations significantly hinder the wider application of BAT and urge the development of alternative testing, such as the mast cell activation test (MAT). The essential difference between BAT and MAT is the heterogeneity of the starting material used to perform the assays. Mast cells are tissue-resident, so cannot be easily accessed. Current alternative sources for functional studies are generating primary human mast cells, differentiated from donor progenitor cells, or using immortalized mast cell lines. Hence, the methodological approaches for MAT are not only vastly different from BAT, but also different among MAT protocols. This review summarizes the advantages and disadvantages of BAT and MAT assays, dedicating special attention to elucidating the key differences between the cellular sources used and provides an overview of studies hitherto performed comparing BAT and MAT in the diagnosis of IgE-mediated food and drug allergies.


Subject(s)
Basophil Degranulation Test , Basophils , Hypersensitivity , Mast Cells , Humans , Mast Cells/immunology , Basophils/immunology , Basophils/metabolism , Basophil Degranulation Test/methods , Hypersensitivity/diagnosis , Hypersensitivity/immunology , Animals , Immunoglobulin E/immunology , Immunoglobulin E/blood
11.
J Immunol Methods ; 529: 113679, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679364

ABSTRACT

The type II autoimmune subtype of Chronic Spontaneous Urticaria (CSU) is characterized by the presence of IgG autoantibodies targeting IgE or the IgE high-affinity receptor (FcεRI) on mast cells and basophils. In evaluation of CSU patients, indirect basophil activation testing (BAT), has been utilized, involving the mixing of patient serum with heterologous peripheral blood donors, followed by flow cytometric assessment of basophil markers. However, the reliability of the indirect BAT results hinges on the quality of the donor basophils utilized. In this study, we introduce an innovative approach where multiple potential basophil donors undergo rigorous BAT characterization alongside control samples. By selecting and pooling donors with optimal performance, we significantly enhance the inter-assay reproducibility of the indirect BAT test.


Subject(s)
Basophils , Chronic Urticaria , Flow Cytometry , Humans , Basophils/immunology , Chronic Urticaria/immunology , Chronic Urticaria/diagnosis , Chronic Urticaria/blood , Flow Cytometry/methods , Reproducibility of Results , Basophil Degranulation Test/methods , Adult , Female , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Autoantibodies/blood , Autoantibodies/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Middle Aged , Receptors, IgE/immunology , Blood Donors
12.
BMC Immunol ; 25(1): 23, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678193

ABSTRACT

BACKGROUND: Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy. METHODS: Seventeen patients with an insect venom allergy were included in the study. The established "BAT 1" utilizes conventional antibody solutions of anti-CCR3 for basophil identification and anti-CD63 to assess basophil activation, whereas "BAT 2" uses dried anti-CD45, anti-CD3, anti-CRTH2, anti-203c and anti-CD63 for identification and activation measurement of basophils. Negative and positive controls as well as incubations with honey bee venom and yellow jacket venom at three concentrations were performed. RESULTS: Seven patients had to be excluded due to low basophil counts, high values in negative controls or negative positive controls. For the remaining 10 patients the overall mean (± SD) difference in activated basophils between the two tests was 0.2 (± 12.2) %P. In a Bland-Altman plot, the limit of agreement (LoA) ranged from 24.0 to -23.7. In the qualitative evaluation (value below/above cut-off) Cohen's kappa was 0.77 indicating substantial agreement. BAT 2 took longer to perform than BAT 1 and was more expensive. CONCLUSION: The BAT 2 technique represents an interesting innovation, however, it was found to be less suitable compared to an established BAT for the routine diagnosis of insect venom allergies.


Subject(s)
Basophils , Flow Cytometry , Humans , Basophils/immunology , Female , Male , Adult , Middle Aged , Flow Cytometry/methods , Arthropod Venoms/immunology , Pilot Projects , Animals , Hypersensitivity/immunology , Hypersensitivity/diagnosis , Insect Bites and Stings/immunology , Insect Bites and Stings/diagnosis , Bee Venoms/immunology , Young Adult , Aged , Antibodies/immunology , Adolescent , Basophil Degranulation Test/methods , Venom Hypersensitivity
13.
Front Immunol ; 15: 1392099, 2024.
Article in English | MEDLINE | ID: mdl-38686384

ABSTRACT

Background: Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Methods: Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Results: Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Conclusions: Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment.


Subject(s)
Anaphylaxis , Asparaginase , Basophils , Drug Hypersensitivity , Immunoglobulin E , Animals , Asparaginase/adverse effects , Asparaginase/immunology , Basophils/immunology , Basophils/metabolism , Mice , Drug Hypersensitivity/immunology , Drug Hypersensitivity/diagnosis , Anaphylaxis/immunology , Anaphylaxis/chemically induced , Immunoglobulin E/immunology , Immunoglobulin E/blood , Female , Disease Models, Animal , Biomarkers , Immunoglobulin G/immunology , Immunoglobulin G/blood , Antineoplastic Agents/adverse effects
14.
Nat Commun ; 15(1): 3389, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649353

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis.


Subject(s)
B7-H1 Antigen , Basophils , Interleukin-4 , Lupus Erythematosus, Systemic , T Follicular Helper Cells , Adult , Animals , Female , Humans , Male , Mice , Middle Aged , Autoantibodies/immunology , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Basophils/immunology , Basophils/metabolism , Cell Differentiation/immunology , Interleukin-4/metabolism , Interleukin-4/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Lupus Nephritis/immunology , Lupus Nephritis/pathology , Lupus Nephritis/metabolism , Mice, Inbred C57BL , T Follicular Helper Cells/immunology , T Follicular Helper Cells/metabolism , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism
15.
Int Immunopharmacol ; 132: 112023, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38603859

ABSTRACT

BACKGROUND: Eosinophils and basophils are implicated in allergic reactions, and the molecule CD200 on B cells may have regulatory functions. Assessing the associations between the expression of CD200 on B lymphocytes and eosinophils and basophils helps unravel the complex immune interactions in atopic dermatitis, aiding in targeted therapeutic approaches. OBJECTIVE: The aim of our study is to evaluate the association between the count of eosinophils, basophils, CD16+ eosinophils, CD203+ basophils, the expression of activation marker CD200 on B cells and on their subsets in patients suffering from atopic dermatitis with and without dupilumab and in control group. MATERIALS AND METHODS: Altogether we examined 75 subjects: 45 patients suffering from atopic dermatitis -32 patients without dupilumab treatment, 13 patients with dupilumab treatment and 30 subjects as a control group. 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 with calculation of R2 (%, percent of Variation Explained). RESULTS: In patients with dupilumab therapy we confirmed the association between absolute eosinophils and expression of molecule CD200 on total B lymphocytes (in 23.9 %), non-switched (in 27.2 %), naive (in 25 %) and memory (in 20.3 %) B lymphocytes and between relative eosinophils and expression of CD200 on total B lymphocytes (in 22.8 % %), non-switched (in 29 %), naive (in 21.3 %) and memory (in 22.3 %) B lymphocytes. This association is low in AD patients without dupilumab and even non linear in control healthy subjects. CONCLUSION: The higher association between eosinophils and expression of CD200 molecule on memory, naive and non switched B lymphocytes in AD patients under dupilumab therapy suggests that activation of B lymphocytes is caused by IL-4, whose production involves eosinophils and the CD200 molecule on B lymphocytes.


Subject(s)
Antibodies, Monoclonal, Humanized , Antigens, CD , B-Lymphocytes , Basophils , Dermatitis, Atopic , Eosinophils , Humans , Dermatitis, Atopic/immunology , Dermatitis, Atopic/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Basophils/immunology , Eosinophils/immunology , Eosinophils/drug effects , Male , Female , Adult , Antigens, CD/metabolism , Antigens, CD/immunology , Pilot Projects , B-Lymphocytes/immunology , B-Lymphocytes/drug effects , Middle Aged , Young Adult , Leukocyte Count
16.
Schizophr Res ; 267: 24-31, 2024 May.
Article in English | MEDLINE | ID: mdl-38513331

ABSTRACT

BACKGROUND: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. METHODS: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. RESULTS: Monocyte counts (OR = 1.91; 95 % CI = 1.07-3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01-1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03-2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01-1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. CONCLUSION: This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period.


Subject(s)
Basophils , Monocytes , Recurrence , Schizophrenia , Humans , Male , Female , Adult , Follow-Up Studies , Schizophrenia/blood , Young Adult , Leukocyte Count , Psychotic Disorders/blood , Inflammation/blood , Adolescent , Prognosis
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