Specific Immunoglobulin Research Articles

Wide possibilities of topical therapy in the treatment of patients with infectious and inflammatory diseases of the pharynx

Despite medical advances, infectious and inflammatory upper respiratory diseases are the most common groups of diseases among outpatients. Viruses induce acute respiratory diseases in most patients; however, bacterial and “atypical” pathogens can cause exacerbations of chronic diseases such as adenoiditis, tonsillitis, pharyngitis and others. Prescribing etiotropic drugs to patients with infectious and inflammatory diseases of the pharynx can reduce the effectiveness of the therapy due to the growth of antimicrobial resistance. Increasing etiotropic drug resistance of some pathogens requires the selection of alternative agents for patients with infectious and inflammatory diseases of the pharynx. The non-specific prophylaxis of the latter is aimed to activate inner defense mechanisms using bacterial lysates (BL). Based on a review of the literature, the article discusses the features of the use and clinical effectiveness of topical BL in infectious and inflammatory diseases of the pharynx. BL are an important supplementation to the standard therapy regimen for inflammatory upper respiratory diseases, which contributes to the restoration of the immune response autoregulation, a reliable decrease in the frequency and duration of acute forms and exacerbations of chronic upper respiratory diseases, and reduced use of antibiotics and antipyretics. Evidence of possible mechanisms to correct immunity in infectious and inflammatory diseases of the pharynx, as well as a review of the clinical effectiveness of the medicine was demonstrated by example of Imudon. Its beneficial use to treat disease in the acute period is associated with its focal action on the infectious and inflammatory lesions. The drug is effective at any stage of the disease and can be used for prophylactic purposes due to activation of mucosal immunity in the respiratory tract. The high efficiency of Imudon is determined by its ability to activate phagocytosis and production of specific immunoglobulins by plasma cells, which reduces the risk of relapses and chronicity of the disease.

Immunological quality of colostrum and specific antibodies against enteropathogens in the colostrum and transition milk of crossbred Gir × Holstein cows.

Colostrum management is crucial for enhancing the immune response against enteropathogens and the survival of dairy calves during the first few weeks of life. However, few physiological studies have investigated the dynamics of general and specific immunoglobulin G (IgG) content in cow milk during early lactation stages, particularly in that of crossbred Gir × Holstein dairy cows, the most predominant dairy cattle population in tropical countries, such as Brazil. Therefore, this study evaluated the effects of parity and milking order on the volume and quality of colostrum, transition milk, and mature milk in crossbred Gir × Holstein cows using three traditional on-farm tests. The dynamics of IgG in the mammary secretions and the specific antibody levels against enteropathogens were also determined using sandwich enzyme-linked immunosorbent assay (ELISA) during the early stages of lactation. Fifty healthy Gir × Holstein cows were divided into two groups based on parity number, i.e., primiparous (n = 18) and multiparous (n = 33). They were monitored from the first to the 43rd milking. The colostrum volume and quality were evaluated using a colostrometer, Brix refractometer, and Colostro Balls after the first milking, in addition to the colostral IgG levels measured using sandwich ELISA as a reference standard. On-farm tests showed that the colostrum samples obtained from Gir × Holstein cows exhibited an optimal colostrum quality based on the literature criteria, regardless of parity number; however, the IgG mass was higher in the colostrum of multiparous (201 ± 67.03g) cows than in that of primiparous (144 ± 32.40g) cows. The volume and composition of transition and whole milk were also assessed at the second to ninth, 11th, 13th, 15th, 29th, and 43rd milkings. Multiparous cows produced higher volumes of transition milk than primiparous cows. In addition, multiparous cows exhibited a higher total solids percentage in their postpartum mammary secretions than primiparous cows. A higher percentage of inhibition of specific antibodies against Escherichia coli K99 was observed in the blood serum of multiparous cows than in that of primiparous cows. The volume and composition of mammary secretions changed over time; milk production increased, whereas total solids, total IgG, and specific antibody levels against most enteropathogens decreased, regardless of parity. Additionally, an association between parity and time was observed with respect to milk yield, the Brix score (%), and specific antibody levels against the Clostridium perfringens alpha toxin in mammary sections and against coronavirus and rotavirus in blood samples. This association indicated higher values in multiparous cattle than in primiparous cattle at specific time points. In conclusion, this study reveals postpartum time-dependent changes in the physiological and immunological components in the mammary secretions and blood of crossbred Gir × Holstein cows from the first to the 43rd milking. These results will contribute to the development of future research in Gir × Holstein-specific neonatology, which is genetically adapted to tropical and subtropical countries.

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.

From bite to brain: Neuro-immune interactions in food allergy.

Immunoglobulin E (IgE)-mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity. While being the gold standard for diagnosis, oral food challenges are burdensome, and diagnostic tools based on specific IgE can be flawed. Furthering our understanding of the mechanisms behind food allergy onset, severity and persistence could help reveal immune profiles associated with the disease, to ultimately aid in diagnosis. Alterations to cytokine levels and immune cell ratios have been identified, though further research is needed to fully capture the heterogenous nature of food allergy. Moreover, the existence of such immune alterations also raises the question of potential wider systemic effects. For example, recent research has emphasised the existence and impact of neuro-immune interactions and implicated behavioural and neurological changes associated with food allergy. This review will provide an overview of such food allergy-driven neuro-immune interactions, with the aim of emphasising the importance of furthering our understanding of the immune mechanisms underlying IgE-mediated food allergy.

Allergic rhinitis: a brief overview of the etiopathogenesis and rehabilitation of patients

The article presents a brief overview of modern literature sources concerning the prevalence, etiopathogenetic approaches in the diagnosis and treatment of allergic rhinitis. The relevance of the problem under consideration is due to the high prevalence of this pathology, the variety of etiopathogenetic mechanisms and the variability of classifications. One of the most popular classifications is seasonal. When studying pathogenetic mechanisms, the following patterns were revealed: the nasal mucosa is the main air conditioner of the respiratory tract and the first line of defense against infectious agents transmitted by airborne droplets. These roles require maintaining and restoring epithelial integrity and the ability to initiate immune responses. When conditions or factors are present that compromise the integrity of the mucosa, the epithelium releases alarmins and other molecular patterns associated with damage that trigger repair mechanisms but can also cause protective inflammation. In allergic rhinitis, the same mechanisms can activate the development of the disease. Many authors consider various diagnostic methods for allergic rhinitis. Such as a detailed and competent collection of complaints and anamnesis, including family history, physical examination, endoscopic examination of the nasal cavity, rhinomanometry, skin prick tests, radiological studies, including computed tomography of the paranasal sinuses, intradermal tests, study of total and specific immunoglobulins E in blood serum, basophil activation test, nasal provocation test, nasal cytology and biopsy histology, acoustic rhinometry, nasal inspiratory peak flow testing, and nitric oxide measurements are used. Attention is also paid to laboratory and instrumental methods for the differential diagnosis of rhinitis of pseudoallergic origin; the following methods are used: ultrasound diagnostics of the hepatobiliary system, biochemical blood test, and immunological studies. Treatment of patients with allergic rhinitis requires an integrated and interdisciplinary approach and, of course, requires differential and personalized methods taking into account etiopathogenetic mechanisms.

Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.

Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines. We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay. Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.

Revealing disease subtypes and heterogeneity in common variable immunodeficiency through transcriptomic analysis

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced levels of specific immunoglobulins, resulting in frequent infections, autoimmune disorders, increased cancer risk, and diminished antibody production despite an adequate B cell count. With its clinical manifestations being highly variable, the classification of CVID, including the widely recognized Freiburg classification, is primarily based on clinical symptoms and genetic variations. Our study aims to refine the classification of CVID by analyzing transcriptomics data to identify distinct disease subtypes. We utilized the GSE51405 dataset, examining transcriptomic profiles from 30 CVID patients without complications. Employing a combination of clustering techniques—KMeans, hierarchical agglomerative clustering, spectral clustering, and Gaussian Mixture models—and differential gene expression analysis with R’s limma package, we integrated molecular findings with demographic data (age and gender) through correlation analysis and identified common genes among clusters. Three distinct clusters of CVID patients were identified using KMeans, Agglomerative Clustering, and Gaussian Mixture Models, highlighting the disease’s heterogeneity. Differential expression analysis unveiled 31 genes with variable expression levels across these clusters. Notably, nine genes (EIF5A, RPL21, ANP32A, DTX3L, NCF2, CDC42EP3, CHP1, FOLR3, and DEFA4) exhibited consistent differential expression across all clusters, independent of demographic factors. The study recommends categorizing patients based on the four genes, NCF2, CHP1, FOLR3, and DEFA4—as they may assist in prognostic prediction. Transcriptomic analysis of common variable immunodeficiency (CVID) patients identified three distinct clusters based on gene expression, independent of age and gender. Nine differentially expressed genes were identified across these clusters, suggesting potential biomarkers for CVID subtype classification. These findings highlight the genetic heterogeneity of CVID and provide novel insights into disease classification and potential personalized treatment approaches.

Intestinal microbiota in children with bronchial asthma

Background. Intestinal microbiota is one of the most important factors determining the state of human health, including its influence on the immunological mechanisms regulating the development of allergic diseases in childhood. The role of intestinal microbiota and the gut – lung axis in the development of bronchial asthma (BA) is an important area of research.Aim. To analyze the taxonomic composition of intestinal microbiota in children with BA using 16S rRNA gene sequencing.Materials and methods. The study included patients with BA (n = 50, mean age 10.34 ± 2.99 years) and a group of apparently healthy individuals (n = 49, mean age 10.3 ± 2.8 years). For all patients, medical history was taken, and physical examination and stool test were performed. Patients with BA were assessed for the level of total and specific immunoglobulin (Ig) E and underwent spirometry. The microbiota composition was analyzed by 16S rRNA gene sequencing with subsequent bioinformatic and statistical analysis.Results. Significant differences in the composition of the intestinal microbiota (beta diversity) and a decrease in taxonomic diversity (alpha diversity) were found in patients with BA compared to healthy controls. The intestinal microbiota of patients with BA was characterized by an increase in the abundance of Bacteroides, Parabacteroides, Lachnospira, Roseburia, Akkermansia, Anaerostipes, Sutterella, Odoribacter, Phascolarctobacterium, Butyricimonas, as well as unclassified bacteria from the Rikenellaceae families. The intestinal microbiota of children without BA was characterized by greater abundance of bacteria from Blautia, Bifidobacterium, Dorea, Ruminococcus, Streptococcus, Eubacterium, Acinetobacter, Collinsella, Lactococcus, Catenibacterium genera and unclassified bacteria from the Clostridiaceae and Coriobacteriaceae families. Significant differences in the quantitative abundance of bacteria were revealed depending on the type of sensitization, the level of total IgE, and the value of FEV1.Conclusion. The results obtained indicate the differences in the intestinal microbiota composition in children with BA and healthy children.

Prevalence of Toscana Virus Antibodies in Residents of Bulgaria: A Nationwide Study Following the Pandemic of COVID-19.

Introduction: Toscana virus (TOSV) is an arthropod-borne virus transmitted by sandflies and is mainly found in countries around the Mediterranean basin. In this article, we present the findings of a seroprevalence study on TOSV in Bulgaria. We aim to assess the current epidemiological situation regarding TOSV in the country and raise clinical awareness. Methods: Serum samples (n = 1892) were collected in December 2023. Serological tests were performed using a commercial anti-TOSV ELISA kit. Results: Specific immunoglobulin G (IgG) antibodies were detected in 6.4% (121/1892) of the participants. A significantly higher seropositivity rate was found in the age group over 65 years compared with the age groups 18-29 and 40-64 (11.8% vs. 3.9% vs. 3.4%), as well as in males compared with females (8.0% vs. 5.3%). The seroprevalence rates in districts ranged from 0% to 18.5%. Higher seropositivity was found in the southern and northern regions. Conclusions: The seroprevalence rate of TOSV in Bulgaria, found in this study, is a significant decrease compared with the seropositivity rate of 24.5% reported in the country in 2018. The reasons for this are unknown and could possibly be related to the COVID-19 pandemic and the constantly changing environmental conditions. There is also a possibility that the higher seropositivity detected in 2018 together with the rise in clinical cases reported from endemic countries around that time might have been due to an unrecognized TOSV outbreak taking place in this period. Continued clinical awareness and surveillance are necessary for recognition and management of potential cases of TOSV neuroinfection, especially during summer.

Innovative Cancer Immunotherapy with MAGE-A3 mRNA Cancer Vaccines.

Cancer causes over 10 million deaths annually worldwide and remains a significant global health challenge. This study investigated advanced immunotherapy strategies, focusing on mRNA vaccines that target tumor-specific antigens to activate the immune system. We developed a novel mRNA vaccine using O,O'-dimyristyl-N-lysyl aspartate (DMKD) to improve stability and phosphatidylserine (PS) to enhance antigen presentation to immune cells. This vaccine, containing melanoma-associated antigen A3 (MAGE-A3) mRNA encapsulated within lipid nanoparticles (LNPs), was evaluated for its therapeutic potential against colorectal cancer. Our findings demonstrated that MAGE-A3 mRNA-containing DMKD-PS LNPs significantly reduced tumor size and weight, effectively combating metastatic cancer. The vaccine elicited a robust immune response, increasing specific immunoglobulin and cytokine levels without causing histotoxicity in major organs. These results confirm that the DMKD-PS-based MAGE-A3 mRNA vaccine holds promise for cancer prevention and treatment.

Seroprevalence of human papilloma virus 6, 11, 16 and 18 among pregnant women in Mwanza-Tanzania

IntroductionHigh-risk human-papilloma viruses 16 and 18 (HR-HPV 16 and HR-HPV-18) are well known to be associated with carcinoma of the cervix, head and neck, penis, and anus. Low-risk human papillomaviruses 6 and 11 (LR-HPV 6 and LR 11) infection has been associated with anogenital warts, oral papilloma, and laryngeal papillomatosis in children. HPV infection during pregnancy (HR-HPV and LR-HPV) increases the risk of vertical transmission from infected pregnant women to unborn children. The burden of HR-HPV type 16 and 18 and LR-HPV 6 and 11 is not well documented among pregnant women attending antenatal clinics (ANC). This study determined the seroprevalence and distributions of HR-HPV 16, 18, and LR –HPV 6, 11 antibodies among pregnant women attending ANC at Bugando Medical Centre (BMC) in Mwanza, Tanzania.MethodologyA cross-sectional study involving 255 pregnant women enrolled in obstetrics and gynecology outpatient clinics was conducted between November 2020 and March 2021 at Bugando Medical Centre (BMC) in Mwanza. A structured pre-tested questionnaire was used to obtain patients’ information. Sandwich Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect HPV 6, 11, 16 and 18 specific immunoglobulin G (IgG) from sera. Stata version 15v1 was used for the descriptive data analysis.ResultsThe median age was 27(IQR: 22–31) years. The overall HPV seropositivity for any of the four serotypes was 63.9% (165/255), 95% CI: 58.0-69.7, whereby 37.6%(97/255), 32.2%( 83/255), 15.5% (40/255) and 27.1% (70) were positive for HPV 6, 11, 16 and 18 respectively. Eight participants (3.1%) were positive for all 4 genotypes.ConclusionAbout two-thirds of pregnant women had antibodies against HPV 6, 11 16, and 18 indicating previous HPV exposure. Vaccination programs should be emphasized to reduce the HPV-related manifestations in this population.

Shrimp allergy leading to severe transfusion reaction: A case report

AbstractBackgroundTransfusion reactions occur at an estimated incidence of 2 per 1.000 transfused products. Anaphylactic transfusion reactions are rarer, and seen in 1 per 10.000 transfusions, and are mostly related to platelet transfusions. Here, we describe a rare cause of a transfusion reaction.Case presentationA 19‐year‐old man underwent an allogeneic haematopoietic stem cell transplantation for sickle cell disease and developed an anaphylactic shock following a platelet transfusion, after excluding all common causes. The patient reported a shrimp allergy, and one of the blood/platelet donors had consumed shrimp the day before donation. Elevated levels of specific immunoglobulin E (IgE) against shrimp and tropomyosin were found in the patient. Subsequent transfusions were performed with apheresis platelets from selected donors who were instructed to avoid shrimp consumption, and these transfusions were uneventfully.ConclusionWhen a severe transfusion reaction occurs in a patient with a known food allergy, an IgE‐mediated (food‐related) transfusion reaction should be considered after excluding other causes.

Mysterious Allergy Caused by Tick Bite: Alpha-Gal Syndrome.

Alpha-Gal syndrome (AGS) manifests as an intricate allergic response characterised by the formation of specific immunoglobulin E (IgE) antibodies targeting a carbohydrate termed galactose-a-1.3-galactose (a-Gal). Alpha-Gal antigens, which play a role in AGS, have been detected in the salivary glands and saliva of various tick species, especially Amblyomma americanum. Identifying these antigens in tick saliva underlines the potential role of tick bites in sensitising individuals to a-Gal and contributes to the complex immunological processes associated with AGS. When people with a-Gal allergy eat beef, pork, lamb, or the flesh of other mammals, they experience an allergic reaction that causes various symptoms, including rash, nausea, vomiting, and diarrhoea. In some cases, AGS can be life-threatening requiring emergency medical attention. Moreover, these reactions do not occur only due to red meat; intake of medical drugs, vaccines, and antidotes containing a-Gal epitopes can also trigger allergies. The fact that the symptoms causing IgE antibodies are directed against a carbohydrate moiety the unusual delay between food consumption and the onset of symptoms, and the differences in the reactions shown by a-Gal allergy make a-Gal syndrome an unprecedented allergic disease and distinguish it from other food allergies. Interestingly, a-Gal antigens involved in the development of AGS have been discovered in salivary secretions of different tick species in several continents. However, the underlying causes of a-Gal-specific IgE production and immune responses to tick bites are not fully understood. This complex system is crucial for identifying and developing new therapies for the disease. This article reviews the evolution of a-Gal, the current understanding of AGS and its relationship to tick species.

Epidemiological and clinical characteristics of cases and detection of pathogens’ markers of tick-borne infections in the Tomsk region

BACKGROUND: Among the spectrum of the tick-borne infections, Lyme borreliosis and tick-borne encephalitis are most often recorded in the Tomsk region, however it is obviously that possible range of the pathogens is not limited to these ones. AIM: To make epidemiological and clinical characteristics of cases and detect frequencies of pathogen’s markers of tick-borne infections among adult patients applying serological and molecular genetic techniques in the Tomsk region during 2020–2023. METHODS: A single-center prospective sample study was conducted applying a comprehensive approach in peripheral blood specimens obtained from 197 patients with suspected tick-borne infections hospitalized during 2020–2023. To verify the diagnoses of tick-borne encephalitis or Lyme borreliosis, specific immunoglobulins of classes M and G to the antigens of virus of tick-borne encephalitis and Borrelia burgdorferi s.l. were determined in paired blood serum samples applying enzyme-linked immunosorbent assay. Additionally, the polymerase chain reaction was used to detect genetic markers of virus of tick-borne encephalitis, B. burgdorferi s.l., B. miyamotoi, Rickettsia spp., Coxiella burnetii, and Francisella tularensis. Epidemiological surveillance data of incidence rates of tick-borne infections obtained from official reports were analyzed as well. MS Office Excel 2010 software was used to calculate frequency morbidity measures. RESULTS: We verified the final diagnosis of tick-borne encephalitis in 52 (26.4%) patients, Lyme borreliosis in 116 (58.9%) patients, co-infection of tick-borne encephalitis and Lyme borreliosis 15 (7.6%) patients, hard tick relapsing fever caused by B. miyamotoi in 8 (4.1%) patients, coinfection of Q fever caused by C. burnetii with tick-borne encephalitis or Lyme borreliosis in 4 (2.0%) patients, and coinfection of tularemia with tick-borne encephalitis or Lyme borreliosis in 2 (1.0%) cases. We identified markers of tick-borne encephalitis and Lyme borreliosis pathogens by polymerase chain reaction in 3.6% and 4.1% of the patients. Most number of individuals with tick bites, and the highest incidence rates of Lyme borreliosis and tick-borne encephalitis were recorded in the suburbs of Tomsk. The age groups of 40–59 years, and elderly people 60 years and older were predominated among the patients. CONCLUSIONS: It was found out that, in addition to Lyme borreliosis and tick-borne encephalitis, there were such tick-borne infections as tick relapsing fever, Q fever, and tularemia in the Tomsk region in the 2020–2023 period.

B-056 Clinical and Analytical Performance Evaluation of Two Immunoassays for the Detection of Mite Specific Serum IgE for Allergy Diagnosis

Abstract Background IgE-mediated allergic diseases can be considered a modern epidemic, with exponential growth mainly in industrialized countries. Diagnosis is usually based on detailed medical history, physical examination, skin or challenge test and the determination of allergen-specific serum IgE - a laboratory test that has become a high-value tool in the allergy patient's journey over the last three decades. As the identification of specific immunoglobulin E (sIgE) for a given allergen is important to aid in the allergy diagnosis, several methods for detecting IgE in vitro are available worldwide and, in recent years, there have been several improvements in laboratory methodologies bringing greater advances in terms of clinical and analytical performance. The study aims to evaluate the clinical performance and correlation between two different sIgE assays (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and their concordance with Skin Prick Test (SPT) and clinical history. Methods This prospective study was conducted with approximately 130 consecutive patients who underwent evaluation of allergic diseases in different centers in Brazil. Clinical data, blood samples, and SPT results were collected. With the blood samples, the allergens D1, D2 and D201 were evaluated using both methods (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and the data were evaluated in a correlation study and clinical concordance analysis. Results Qualitatively evaluating the sIgE results between the two immunoassays, at the cutoff point considered clinically significant (≥ 0.35 KU/L), a total agreement of 95.2% (D1); 95.1% (D2), 91.7% (D201) and 96.8% (Derp2) was observed. Semi-quantitatively evaluating through reactive interpretation, an agreement of 89.5% (D1); 91.06% (D2); 87.60% (D201) and 93.33% (Derp2) was observed. Spearman's correlation between the analytical methods was 0.85 (D1), 0.93 (D2), 0.68 (D201) and 0.76 (Derp2). When compared with the SPT results, a total agreement of 78.7% and 80.1% was obtained for 3gAllergy and ImmunoCAP, respectively, with slightly higher positive agreement for both methods. Conclusions The two methods have good agreement with each other, with greater differences when evaluated quantitatively. However, when compared to clinical history and skin prick test results, both perform very similarly with a few differences that may be caused by the difference in the assay design.

Sub-Optimal Disease Control and Low Blood Eosinophil Testing Frequency in Chinese Adult Patients with Asthma Receiving GINA Step 4/5 Treatment: A Real-World Study.

To inform effective management strategies for severe asthma in China, this study aimed to comprehensively characterize clinical characteristics, treatment patterns, disease control status, and healthcare resource utilization among patients on GINA Step 4/5 therapies by analyzing data from the Adelphi Asthma Disease Specific Program conducted in China. All information was retrieved from medical records or collected from physicians and patients on the survey date (August-December 2018); no follow-up was conducted. Results were summarized descriptively for patients on GINA Step 4/5 therapies, who were pooled from a consecutive sample (comprising three or more consecutive patients with physician-diagnosed asthma from each participating physician) and an oversample (comprising the next two patients with physician-perceived severe asthma from each participating physician). Of the included patients (n=754), 51.5% had ever had a blood eosinophil measurement taken, 22.1% had available records for their most recent blood eosinophil measurements (68.9% of them had an elevated level ≥150 cells/µL), 39.9% had ever been tested for specific immunoglobulin E or radioallergosorbent, and 8.0% were prescribed maintenance oral corticosteroids. Asthma was not well controlled in 69.2% of patients. In the prior year, 27.1% experienced at least one severe exacerbation and 22.8% experienced at least one hospitalization (emergency visit or overnight stay) due to asthma. In Chinese patients with asthma on GINA Step 4/5 therapies, biomarker testing was underutilized, asthma was not well controlled, and severe exacerbations were not infrequent. These findings highlight the urgent need for optimized asthma management for patients on GINA Step 4/5 therapies in China.

An exceptionally large wave of M. pneumoniae infections among children in Tianjin post COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has caused a persistent lowering of Mycoplasma pneumoniae (M. pneumoniae), which is commonly found in children with respiratory tract infections (RTIs). However, in 2023, we observed an unusually high number of M. pneumoniae infections among children from Tianjin, the second largest city in northern China. This study sought to analyze the epidemiological characteristics of children with RTIs caused by M. pneumoniae in northern China post COVID-19, in order to provide a theoretical basis for clinical diagnosis and treatment. Between January 2019 and December 2023, a total of 78,886 children with respiratory infections from General Hospital of Tianjin Medical University were included in this study. A rapid immunochromatographic assay kit was used to test for M. pneumoniae specific immunoglobulin M (IgM) in these patients. The relevant clinical data of M. pneumoniae-positive cases were also collected, and analyzed by SPSS software. Out of the 78,886 samples collected, a total of 11,268 tested positive for M. pneumoniae specific-IgM antibody. The average positive rate was 14.3% in the past 5 years. In the year 2023 alone, there were 5,870 M. Pneumoniae positive cases, surpassing the combined count from the previous 4 years. The incidence of M. pneumoniae had significantly surged since September 2023, peaking at 1,717 cases in November 2023, with a notable surge during the fourth quarter. The prevalence of M. pneumoniae infection was primarily observed among children aged 4-6 years and 7-9 years both before and during the COVID-19 pandemic; however, a noticeable increase was observed among children aged 10-14 years after the pandemic ended. Boys exhibited a lower positive rate (13.19%) compared to girls (15.56%). In addition, the proportion of pneumonia cases in 2023 was significantly higher than that in previous years (P<0.001). Our study revealed that following a prolonged global lowering of M. pneumoniae since the COVID-19 pandemic, a significant outbreak had emerged in northern China since September 2023. The proportion of M. pneumoniae positive children in the older age group increased in 2023 compared to that observed in 2019. Additionally, there was an increase in the proportion of pneumonia among M. pneumoniae positive cases in 2023 compared to the pre-COVID-19 pandemic period.

Role of specific immunoglobulin-E in chronic rhinosinusitis: Its clinical relevance according to nasal challenge test

BackgroundGuidelines for chronic rhinosinusitis (CRS) propose total IgE and eosinophils as important biomarkers to identify type-2 inflammation. Despite the fact that specific IgE (sIgE) have been identified as a clinical predictor in some type-2 diseases for different clinical outcomes, its role in CRS has yet to be explored in detail. ObjetiveTo describe systemic and local sIgE in CRS and explore its possible association with clinical outcomes using nasal challenge tests (NCT). MethodsIn CRS patients, we measure total IgE, serum sIgE (SsIgE) and nasosinusal sIgE (NsIgE) against 9 allergenic sources; Der p, Der f, Blo t, Can f, Fel d, Per a, grasses, Staphylococcus enterotoxin A, and B. NCT was done using the allergen with the higher sIgE prevalence (Der p). ResultsA total of 174 patients were included. Prevalence of SsIgE was 52.8% and NsIgE 46.5%; Der p was the principal allergen for SsIgE and NsIgE. The presence of nasal polyps, asthma comorbidity, NSAID hypersensitivity, and hyposmia, were significantly associated with the presence of SsIgE and NsIgE but not with total IgE. NCT-Der p was performed in 73 CRS patients, being positive in 33 (45.2%). SsIgE have the best diagnostic accuracy (79.4%) to predict NCT results (NsIgE 67.5% total IgE 52%). ConclusionSpecific IgE is a better biomarker in CRS than total IgE. Patients with clinically relevant SsIgE have a pheno-endotype associated with different clinical outcomes. Considering the clinical relevance of SsIgE demonstrated by NCT, interventions like allergen immunotherapy in CRS must be study.

Perinatal administration of Saccharomyces cerevisiae UFMG A-905 prevents asthma development in the offspring of mice.

Asthma prevalence has been increasing in communities that become more urbanised. Our previous results showed that Saccharomyces cerevisiae UFMG A-905 prevented the development of asthma symptoms and characteristics in a dose-dependent manner. Perinatal programming theory proposes that early exposure to some stimuli may have a protective effect in adult life. The aim of this study was to evaluate the effects of perinatal administration of S. cerevisiae UFMG A-905 in the prevention of asthma in the offspring of mice. S. cerevisiae UFMG A-905 was cultured in YPD broth medium and administered to three groups of mice: before conception, during gestation and lactation (CGL group); during gestation and lactation (GL group); and only during lactation (L group). The offspring of these animals were sensitised and challenged with ovalbumin. Two control groups received saline in the same periods. After, in vivo measurements of airway hyperresponsiveness (AHR) were performed. Total and differential cell count in bronchoalveolar lavage (BAL); ELISA for interleukin (IL)-4, IL-5, IL-10, IL-13, and IL-17A in the lung homogenate or BAL; and ELISA for ovalbumin (OVA)-specific immunoglobulin E (IgE) were performed. The animals of the CGL, GL, and L group, when compared to the OVA group, presented a significant reduction of AHR ( P < 0.01), levels of IL-5 ( P < 0.001) in BAL, and IL-4 ( P < 0.05) and IL-13 ( P < 0.01) in the lung homogenate. Serum IgE levels were significantly higher ( P < 0.05) in CGL and GL groups when compared to the OVA group, but not in the L group. Only in the group L, there was a significant decrease in the number of total cells ( P < 0.01) and eosinophils ( P < 0.05). Perinatal administration of S. cerevisiae UFMG A-905 prevented the development of asthma-like characteristics and may be an option for asthma management. The protective effects on the offspring were more prominent when the yeast was given during lactation.

Full-Length Immune Repertoire Reconstruction and Profiling at the Transcriptome Level Using Long-Read Sequencing.

Due to the diversity of the immune repertoire (IR), reconstructing full-length IR using traditional short-read sequencing has proven challenging. A full-length IR sequencing (FLIRseq) work flow was developed with linear rolling circle amplification and nanopore sequencing. Its accuracy and quantification ability were verified by plasmid mixtures and commercial B-cell receptor/T-cell receptor sequencing (BCR/TCR-seq) based on short reads. IRs in tissues and the peripheral blood from 8 patients with acute lymphoblastic leukemia, 3 patients with allergic diseases, 4 patients with psoriasis, and 5 patients with prostate cancer were analyzed using FLIRseq. FLIRseq reads had lower mismatch rates and gap rates, and higher identify rates than nanopore reads (all P < 2.2 × -16). The relative quantification of components by FLIRseq was consistent with the actual quantification (P > 0.05). FLIRseq had superiority over BCR/TCR-seq, providing the long complementarity-determining region 3, B-cell isotype, and the rarely used V gene sequence. FLIRseq observed an increase in clonotype diversity (P < 0.05) and a decrease in the percentage of abnormal BCRs/TCRs in patients with leukemia in remission. For patients with allergic diseases or psoriasis, FLIRseq provided direct insights into V(D)J recombination and specific immunoglobulin classes. Compared with that in prostate cancer tissues, the full-length V segment of the biased T-cell receptor β chain from lymphocytes in psoriatic tissues showed a more consistent AlphaFold2-predicted protein structure (P < 0.05). FLIRseq enables unbiased and comprehensive analyses of direct V(D)J recombination and immunoglobulin classes, thereby contributing to characterizing pathogenic mechanisms, monitoring minimal residual disease, and customizing adoptive cell therapy.