Search

ObjectivePrimary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.MethodsUsing a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.ResultsSaliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new gland-associated immune niche has implications for respiratory health.

BackgroundThere are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies.MethodsIn a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay.ResultsTwo-hundred fifty-six pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least 1 isotype. Symptomatic disease and vaccination before delivery were associated with higher maternal IgG at labor and delivery. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (odds ratio [OR] = 4.0), mild/moderate disease (OR = 4.8), severe/critical disease (OR = 6.3), and maternal vaccination before delivery (OR = 18.8). No factors were significant in the multivariate analysis at 6 months postpartum.ConclusionsVaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

BackgroundA panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders.ObjectivesTo evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases.AnimalsFifty-five dogs with primary intestinal disease.MethodsSerum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points.ResultsTwenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P = .99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs.Conclusions and clinical importanceThe evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.

BackgroundOne potential mechanism for protection from SARS-CoV-2 in children is through passive immunity via breast milk from a mother infected with the novel coronavirus. The primary objectives of this study were to establish the presence of SARS-CoV-2-specific IgA and IgG and to characterize the antigenic regions of SARS-CoV-2 proteins that were reactive with antibodies in breast milk.MethodsBetween March 2020 and September 2020, 21 women with confirmed SARS-CoV-2 infection were enrolled in Mommy's Milk. Participants donated serial breast milk samples around their time of illness. Breast milk samples were used to probe a multi-coronavirus protein microarray containing full-length and variable-length overlapping fragments of SARS-CoV-2 proteins. Samples were also tested against S and N proteins by electrochemiluminescence assay.ResultsThe breast milk samples contained IgA reactive with a variety of SARS-CoV-2 antigens. The most IgA-reactive SARS-CoV-2 proteins were N (42.9% of women responded to ≥1 N fragment) and S proteins (23.9% responded to ≥1 fragment of S1 or S2). IgG responses were similar. A striking observation was the dissimilarity between mothers in antibody recognition, giving distinct antibody reactivity and kinetic profiles.ConclusionsIndividual COVID-19 cases had diverse and unique milk IgA profiles following the onset of symptoms.ImpactIn this observational longitudinal case series of 21 women with confirmed SARS-CoV-2 infection, IgA binding to SARS-CoV-2 proteins detected by orthologous proteome microarray and electrochemiluminescence assays was observed in >75% of women, but there was heterogeneity in which antigens and how many were reactive between women. Immunological profiles of protein regions recognized by each woman were distinct. Diverse repertoires of mucosal breast milk antibody to SARS-CoV-2 reflect heterogeneous passive transfer of maternal antibody to exposed breastfeeding infants.

IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period., SCOPUS: ar.j, info:eu-repo/semantics/published

Inactivated trivalent poliovirus vaccine (IPV) induces humoral immunity, which protects against paralytic poliomyelitis but does not induce sufficient mucosal immunity to block intestinal infection. We assessed the intestinal immunity in healthy adults in Belgium conferred by a co-formulation of IPV with the mucosal adjuvant double mutant Labile Toxin (dmLT) derived from Escherichia coli., SCOPUS: ar.j, info:eu-repo/semantics/published

Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause subsequent infectious events, a nasal vaccine that induces NTHi-specific secretory IgA capable of preventing biofilm formation in the respiratory tract is desirable. Here, we developed a cationic cholesteryl pullulan-based (cCHP nanogel) nasal vaccine containing the NTHi surface antigen P6 (cCHP-P6) as a universal vaccine antigen, because P6 expression is conserved among 90% of NTHi strains. Nasal immunization of mice with cCHP-P6 effectively induced P6-specific IgA in mucosal fluids, including nasal and middle ear washes. The vaccine-induced P6-specific IgA showed direct binding to the NTHi via the surface P6 proteins, resulting in the inhibition of NTHi biofilm formation. cCHP-P6 nasal vaccine thus protected mice from intranasal NTHi challenge by reducing NTHi colonization of nasal tissues and eventually eliminated the bacteria. In addition, the vaccine-induced IgA bound to different NTHi clinical isolates from patients with otitis media and inhibited NTHi attachment in a three-dimensional in vitro model of the human nasal epithelial surface. Therefore, the cCHP-P6 nanogel nasal vaccine induced effective protection in the airway mucosa, making it a strong vaccine candidate for preventing NTHi-induced infectious diseases, such as otitis media, sinusitis, and pneumonia.

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. In this review, we summarize the current knowledge regarding alterations of the IgA/pIgR system observed in those major obstructive airway diseases and discuss their implication for disease pathogenesis.

Idiopathic pulmonary fibrosis (IPF) is a lethal respiratory disease characterized by the excessive deposition of extracellular matrix in the alveolar zones. The bronchiolar epithelium has been implicated in the development of this disease and is capable of secreting IgA into the airway lumen thanks to its expression of the polymeric immunoglobulin receptor. Several elements indicate a dysregulation of this system, such as raised serum IgA levels in IPF patients and the pro-fibrotic effect of IgA on several key cell types. Our work aims at studying the underlying mechanisms so as to better understand the role of IgA mucosal immunity in this disease.

This Brief Review delves into B cell responses in the context of allergy. The primary contribution of B cells to allergy is the production of IgE, the Ab isotype that triggers immediate hypersensitivity reactions through the release of mediators from mast cells and basophils. B cells may also have protective roles in allergy, such as through the production of IgG or as regulatory B cells. In this review, I focus on the basic principles of B cell differentiation and discuss features relevant to allergic immune responses. In particular, I discuss: (1) class-switch recombination; (2) plasma cell differentiation; (3) germinal centers and affinity maturation; and (4) memory B cells and recall responses, with an emphasis on IgE, IgG1, and IgG4. I also consider how B cells may contribute to allergic responses independent of Ab production-for example, by serving as APCs.

Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4+ Tfh cells), which help B cells produce antibodies, were compared between HSV-1-infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that (i) the ASYMP individuals had increased frequencies of HSV-specific CD19+CD27+ memory B cells, and (ii) high frequencies of HSV-specific switched IgG+CD19+CD27+ memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0+CXCR5+CD4+ memory Tfh cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gD+CD138+ B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes. IMPORTANCE Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blindin

QC 20230607

Splenectomy is closely associated with a lifetime risk of pneumococcal and other encapsulated bacterial infections. In this study, it was aimed to investigate the change of antibody levels after vaccination against Streptococcus pneumoniae according to age, gender, years after splenectomy and the possible effect of splenectomy on IgG avidity. In addition the education and awareness levels of the participants about post-splenectomy vaccination and infectious diseases were also analyzed. In the first of the three phases of this study, 32 individuals with splenectomy were enrolled. The awareness of the patients about the possible risks after splenectomy was investigated with a simple questionnaire. Routine laboratory test results were obtained and clinical examinations were performed. In the second stage, total Ig values of 29 splenectomy patients were determined. In the third phase, 14 splenectomy and 5 healthy volunteers were vaccinated according to the Vaccination Practices Advisory Committee (ACIP) guidelines. Pneumococcal-specific antibody levels and IgG avidity were detected by enzyme linked immunosorbent assay (ELISA). It was determined that 68.8% of the splenectomized patients were unaware of their vaccination status and 78.2% of them were unaware of the increased risk of infectious diseases in asplenic conditions. . According to the hospital information management system, all 31 (96.87%) patients, except one, were vaccinated with PPV23. As expected, vaccinated patients exhibited high levels of vaccine-specific antibody production with IgG, IgG2, and IgA antibody concentrations of 321 ± 76.68 mg/l, 73.07 ± 8.273 mg/l, and 117.8 ± 14.94 mg/l, respectively, but unvaccinated patients had very low antibody (IgG, IgG2 and IgA antibody concentrations were 11.5 mg/l, 1.3 mg/l and 1.2 mg/l, respectively) levels. Although there was no correlation between antibody titers and gender, age groups or presence of fever history, the decrease in total IgG, IgG2 and IgA titers w

Splenectomy is closely associated with a lifetime risk of pneumococcal and other encapsulated bacterial infections. In this study, it was aimed to investigate the change of antibody levels after vaccination against Streptococcus pneumoniae according to age, gender, years after splenectomy and the possible effect of splenectomy on IgG avidity. In addition the education and awareness levels of the participants about post-splenectomy vaccination and infectious diseases were also analyzed. In the first of the three phases of this study, 32 individuals with splenectomy were enrolled. The awareness of the patients about the possible risks after splenectomy was investigated with a simple questionnaire. Routine laboratory test results were obtained and clinical examinations were performed. In the second stage, total Ig values of 29 splenectomy patients were determined. In the third phase, 14 splenectomy and 5 healthy volunteers were vaccinated according to the Vaccination Practices Advisory Committee (ACIP) guidelines. Pneumococcal-specific antibody levels and IgG avidity were detected by enzyme linked immunosorbent assay (ELISA). It was determined that 68.8% of the splenectomized patients were unaware of their vaccination status and 78.2% of them were unaware of the increased risk of infectious diseases in asplenic conditions. . According to the hospital information management system, all 31 (96.87%) patients, except one, were vaccinated with PPV23. As expected, vaccinated patients exhibited high levels of vaccine-specific antibody production with IgG, IgG2, and IgA antibody concentrations of 321 ± 76.68 mg/l, 73.07 ± 8.273 mg/l, and 117.8 ± 14.94 mg/l, respectively, but unvaccinated patients had very low antibody (IgG, IgG2 and IgA antibody concentrations were 11.5 mg/l, 1.3 mg/l and 1.2 mg/l, respectively) levels. Although there was no correlation between antibody titers and gender, age groups or presence of fever history, the decrease in total IgG, IgG2 and IgA titers w

Background The efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator's Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16. Objective This post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16. Methods Patients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16. Results Continued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement ver

Giving the vaccine to breastfeeding mothers will provide immunity to the baby through the placenta, umbilical cord (IgG) and breast milk (IgA). The purpose of this study was to analyze differences in IgA levels in breast milk in breastfeeding mothers with the Covid 19 vaccine and without the Covid 19 vaccine. This study used an observational comparative analytic study in 2 unpaired groups with a cross sectional design. The research sites for taking breast milk were in the Working Area of ??Paal Merah I Public Health Center, Jambi City, PMB Rosmala Aini and the Biomedical Laboratory of the Faculty of Medicine, Andalas University for the assessment of breast milk IgA levels. The population in this study were all breastfeeding mothers who had received the Covid-19 vaccine stage 1 and stage 2 and as controls were all breastfeeding mothers who had not received the Covid-19 vaccine in the Paal Merah I Health Center Work Area and PMB Rosmala Aini Jambi City. a sample of 40 respondents. In the univariate analysis, the normality of the data was tested first using Shapiro Wilk. In Bivariate analysis to see the difference in IgA levels with unpaired t test if the data is normally distributed (p value> 0.05), if the data is not normally distributed (p value 0.05) an alternative test is used, namely Mann Whitney. The results showed that the average level of Immunoglobin A in breastfeeding mothers with the Covid-19 vaccine was 2.30 ± 0.44 ng/ml, while the average level of Immunoglobin A in breastfeeding mothers without the Covid-19 vaccine was 2.54 ± 0.45 ng. /ml. The results of the independent t test found that the P-value was 0.10, so it can be concluded that there is no difference in the levels of Immunoglobin A in breast milk between breastfeeding mothers with the Covid-19 vaccine and without the Covid-19 vaccine. The conclusion of the study is that there is no difference in levels of Immunoglobin A in breast milk both in breastfeeding mothers with the Covid-19 vaccine and

Giving the vaccine to breastfeeding mothers will provide immunity to the baby through the placenta, umbilical cord (IgG) and breast milk (IgA). The purpose of this study was to analyze differences in IgA levels in breast milk in breastfeeding mothers with the Covid 19 vaccine and without the Covid 19 vaccine. This study used an observational comparative analytic study in 2 unpaired groups with a cross sectional design. The research sites for taking breast milk were in the Working Area of ??Paal Merah I Public Health Center, Jambi City, PMB Rosmala Aini and the Biomedical Laboratory of the Faculty of Medicine, Andalas University for the assessment of breast milk IgA levels. The population in this study were all breastfeeding mothers who had received the Covid-19 vaccine stage 1 and stage 2 and as controls were all breastfeeding mothers who had not received the Covid-19 vaccine in the Paal Merah I Health Center Work Area and PMB Rosmala Aini Jambi City. a sample of 40 respondents. In the univariate analysis, the normality of the data was tested first using Shapiro Wilk. In Bivariate analysis to see the difference in IgA levels with unpaired t test if the data is normally distributed (p value> 0.05), if the data is not normally distributed (p value 0.05) an alternative test is used, namely Mann Whitney. The results showed that the average level of Immunoglobin A in breastfeeding mothers with the Covid-19 vaccine was 2.30 ± 0.44 ng/ml, while the average level of Immunoglobin A in breastfeeding mothers without the Covid-19 vaccine was 2.54 ± 0.45 ng. /ml. The results of the independent t test found that the P-value was 0.10, so it can be concluded that there is no difference in the levels of Immunoglobin A in breast milk between breastfeeding mothers with the Covid-19 vaccine and without the Covid-19 vaccine. The conclusion of the study is that there is no difference in levels of Immunoglobin A in breast milk both in breastfeeding mothers with the Covid-19 vaccine and

Background: Primary antibody deficiencies (PADs) without an identified monogenetic origin form the largest and most heterogeneous group of primary immunodeficiencies. These patients often remain undiagnosed for years and many present to medical attention in adulthood after several infections risking structural complications. Not much is known about their treatment, comorbidities, or prognosis, nor whether the various immunological forms (decreased total IgG, IgG subclass(es), IgM, IgA, specific antibody responses, alone or in combination(s)) should be considered as separate, clearly definable subgroups. The unclassified primary antibody deficiency (unPAD) study aims to describe in detail all PAD patients without an identified specific monogenetic defect regarding their demographical, clinical, and immunological characteristics at presentation and during follow-up. In constructing these patterns, the unPAD study aims to reduce the number of missed and unidentified PAD patients in the future. In addition, this study will focus on subclassifying unPAD to support the identification of patients at higher risk for infection or immune dysregulation related complications, enabling the development of personalized follow-up and treatment plans. Methods and analysis: We present a protocol for a multicenter observational cohort study using the ESID online Registry. Patients of all ages who have given informed consent for participation in the ESID online Registry and fulfill the ESID Clinical Working Definitions for ‘unclassified antibody deficiency’, ‘deficiency of specific IgG’, ‘IgA with IgG subclass deficiency’, ‘isolated IgG subclass deficiency’, ‘selective IgM deficiency’, ‘selective IgA deficiency’ or ‘common variable immunodeficiency’ will be included. For all patients, basic characteristics can be registered at first registration and yearly thereafter in level 1 forms. Detailed characteristics of the patients can be registered in level 2 forms. Consecut

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

The human body is daily exposed to possible pathogens such as bacteria, viruses, fungi and parasites, as well as to essential non-body food components. The immune system ensures that there is a good balance between tolerating important elements such as the nutrients in our diet on the one hand, and preventing and fighting infections on the other hand. The immune system does this efficiently together with the organs, tissues and cells in the body. Antibodies are important immunological mediators and are produced by our body in different forms called IgA, IgG, IgE, IgD and IgM. IgA is the most predominant antibody at mucosal surfaces and plays an important role in maintaining homeostasis. In the intestinal tract IgA regulates a healthy microbiota composition and it plays an important role in preventing infection and disease. In the unlikely event that pathogens do enter, IgA can form a layer around the pathogen thereby forming a complex. FcαRI-expressing immune cells are activated with IgA complexes and produce more pro-inflammatory compounds compared to activation with IgG complexes. This potent stimulation by IgA is beneficial in elimination of the pathogen. Unfortunately, it can also happen that IgA is not directed against a pathogen, but against the body's own molecules. This so-called auto-IgA can result in tissue damage such as occurs in various autoimmune diseases. Auto-IgA can activate immune cells that have FcαRI on their cell surface and cause a deteriorated condition of the patient. Blocking interactions between IgA and FcαRI is a promising new therapy for IgA-mediated diseases. To maintain the health of the human body, it is therefore important that IgA and the interaction between IgA and FcαRI remain in balance.

Background and Aim: Obtaining duodenal mucosal biopsy samples during gastroduodenoscopy has long been the gold standard in celiac disease (CeD) diagnosis. However, this paradigm was challenged in 2012 by the release of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) non-biopsy criteria. Under the 2020 ESPGHAN guidelines, pediatric patients satisfying the serological criteria may receive a diagnosis of CeD without duodenal biopsy samples and subsequent histological confirmation being obtained. We aimed todetermine the frequency of incidental abnormalities missed by omitting biopsies, in accordance with the 2020 ESPGHAN non-biopsy criteria, in an Australian pediatric population. Method(s): We performed a retrospective case notes review of all patients who had undergone investigation for CeD with subsequent histological diagnosis from 2013 to 2018 at a large tertiary center in Melbourne. Eligible patients were selected on meeting our selection criteria of age < 18 years, anti-tissue transglutaminase IgA > 10 x upper limit of normal (ULN), and deamidated gliadin peptide (DGP) IgA or IgG > 10 x ULN. Our center's pathology database and electronic medical records were consulted to derive the final subset of pediatric patients included in our study. Histopathological reports of all biopsy samples obtained from eligible patients were reviewed, and any incidental abnormalities identified by consultant pathologists were noted. Incidental abnormalities identified were reviewed for clinical significance, which we defined as those potentially requiring further treatment or follow-up. Result(s): During the study period, 252 children were diagnosed with CeD; however, only 44 (17.5%) (25 female, 19 male; median ages, 6 and 7 years, respectively) satisfied our inclusion criteria for non-biopsy diagnosis. A total of 369 biopsy samples were obtained: 260 duodenal (median, 6), 82 gastric (median, 2), and 27 esophageal (median, 2). All patients ha

BackgroundData regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.MethodsFrom a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose).ResultsNo severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.ConclusionsCOVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.

Background and Aim: Obtaining duodenal mucosal biopsy samples during gastroduodenoscopy has long been the gold standard in celiac disease (CeD) diagnosis. However, this paradigm was challenged in 2012 by the release of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) non-biopsy criteria. Under the 2020 ESPGHAN guidelines, pediatric patients satisfying the serological criteria may receive a diagnosis of CeD without duodenal biopsy samples and subsequent histological confirmation being obtained. We aimed todetermine the frequency of incidental abnormalities missed by omitting biopsies, in accordance with the 2020 ESPGHAN non-biopsy criteria, in an Australian pediatric population. Method(s): We performed a retrospective case notes review of all patients who had undergone investigation for CeD with subsequent histological diagnosis from 2013 to 2018 at a large tertiary center in Melbourne. Eligible patients were selected on meeting our selection criteria of age < 18 years, anti-tissue transglutaminase IgA > 10 x upper limit of normal (ULN), and deamidated gliadin peptide (DGP) IgA or IgG > 10 x ULN. Our center's pathology database and electronic medical records were consulted to derive the final subset of pediatric patients included in our study. Histopathological reports of all biopsy samples obtained from eligible patients were reviewed, and any incidental abnormalities identified by consultant pathologists were noted. Incidental abnormalities identified were reviewed for clinical significance, which we defined as those potentially requiring further treatment or follow-up. Result(s): During the study period, 252 children were diagnosed with CeD; however, only 44 (17.5%) (25 female, 19 male; median ages, 6 and 7 years, respectively) satisfied our inclusion criteria for non-biopsy diagnosis. A total of 369 biopsy samples were obtained: 260 duodenal (median, 6), 82 gastric (median, 2), and 27 esophageal (median, 2). All patients ha

In cystic fibrosis (CF), recurrent pulmonary infections suggest lung impaired mucosal immunity. The epithelium and the secretion of immunoglobulin A (IgA) by polymeric immunoglobulin receptor (pIgR) are major lines of mucosal defence. Therefore, this thesis aimed at assessing airway epithelial function (IgA secretion) and differentiation in CF. We observed an enhanced bronchoepithelial pIgR and IgA production in the CF lung, indicating upregulated humoral mucosal immunity due to Th17 host immune response against infection. By contrast, in the absence of infection, cell and animal experiments displayed a negative regulation of pIgR expression upon CFTR F508del mutation, associated with unfolded protein response. We also showed a ciliated cell defect and several signatures of impairment of the airway epithelium integrity, including epithelial-to-mesenchymal transition, in CF lung and cell. In conclusion, this thesis reveals in CF a complex interplay between dedifferentiated epithelial cells and (Pseudomonas aeruginosa) infection, which connects CFTR dysfunction, unfolded protein response activation, and a (Th17) host immune response to IgA secretion in the lung., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2021

Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research - cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifical

BackgroundData regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.MethodsFrom a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose).ResultsNo severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.ConclusionsCOVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.

BackgroundRotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts.MethodsIn this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination.FindingsBetween Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary

Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier–perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

Background: Allergic reactions to blood products are well recognised adverse events. The management of these is the same as for any allergen/s. The Serious Transfusion Incident Reporting (STIR) system focuses on serious reactions rather than minor reactions. Aim(s): To report on the clinical management/investigations of allergic reactions to blood products. Method(s): STIR receives acute event notifications via an online form, triggering a reaction-specific detailed investigation form sent for completion. Severity, treatment at time of reaction and subsequent investigations were analysed against recommendations. Result(s): From July 2012 - June 2018, STIR received 149 reports of allergic/ anaphylactic reactions; 46% of all acute reactions. Reaction severity was validated by expert review and determined to be mild (27%), moderate/ severe (56%), or anaphylactic/anaphylactoid (17%). Reactions related to platelets (69, 46%), FFP (fresh frozen plasma) (51, 34%), RBC (red blood cells) (29, 19%), other (9, 6%). Allergy is a clinical diagnosis; however some investigations will assist in determining likelihood or cause. Although IgA testing is recommended in severe/anaphylactic reactions only 24% were tested. Conclusion(s): Allergic reactions, contingent on the plasma content of blood products are a frequent source of reportable adverse events. Adherence to recommended management and investigation is inconsistent and highlights opportunities to improve knowledge for clinicians. (Table Presented) .

Background: There is no histological classification to predict disease flare in children with IgA nephropathy (IgAN). As macrophage (MQ) accumulation correlates with histological injury, we investigated new histological criteria to predict disease flare in pediatric IgAN. Method(s): A total of 73 children with biopsy proven IgAN underwent 2 years of steroid treatment followed by a protocol biopsy and then steroid tapering. The non-flare group successfully discontinued steroid treatment (N=61, 20.1+/-9.2 years at biopsy); the flare group exhibited increased proteinuria during the taper or cessation of treatment (N=12, 11.6+/-2.3 years at biopsy, p<0.05). Histological findings were evaluated using Oxford classification. Macrophage number and phenotype was assessed by immunofluorescence. Result(s): At first (diagnostic) biopsy, urine findings were comparable between the two groups, but the flare group had a higher serum IgA level (279+/-83 vs 214+/-87 mg/dL; P<0.05). Biopsies revealed no difference in mesangial proliferation (M), endocapillary proliferation (E), glomerulosclerosis (S), tubulointerstitial fibrosis (T), and crescent formation (C); however, the flare group had more total MQ (CD68+ cells) (p<0.05) and M1 MQ (CD68+CD86+ cells) (p<0.05). In addition, M1 MQ correlated with glomerular M, E, S, C lesions (all P<0.01). At second (protocol) biopsy, the flare group had more severe S (p<0.01) and T (p<0.05) lesions, and more glomerular and interstitial M2 MQ (CD68+CD163+ cells) (both p<0.01 vs non-flare group). In addition, M2 MQ correlated with S and T lesions (both p<0.001). ROC analyses revealed glomerular MQ number >2.2 cells at first biopsy could predict disease flare by sensitivity of 83%. Conclusion(s): MQ accumulation is a potential marker to predict disease flare in pediatric IgAN. The number of glomerular M1 MQ in active lesions at the first biopsy was related to flare occurrence, while glomerular and interstitial accumulation of M2 MQ in chronic lesions

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Common Variable Immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are primary antibody deficiencies characterized by hypogammaglobulinemia and recurrent infections, which can lead to structural airway disease (AD) and interstitial lung disease (ILD). We investigated associations between serum IgA, oropharyngeal microbiota composition and severity of lung disease in these patients. In this cross-sectional multicentre study we analyzed oropharyngeal microbiota composition of 86 CVID patients, 12 XLA patients and 49 healthy controls (HC) using next-generation sequencing of the 16S rRNA gene. qPCR was used to estimate bacterial load. IgA was measured in serum. High resolution CT scans were scored for severity of AD and ILD. Oropharyngeal bacterial load was increased in CVID patients with low IgA (p = 0.013) and XLA (p = 0.029) compared to HC. IgA status was associated with distinct beta (between-sample) diversity (p = 0.039), enrichment of (Allo)prevotella, and more severe radiographic lung disease (p = 0.003), independently of recent antibiotic use. AD scores were positively associated with Prevotella, Alloprevotella, and Selenomonas, and ILD scores with Streptococcus and negatively with Rothia. In clinically stable patients with CVID and XLA, radiographic lung disease was associated with IgA deficiency and expansion of distinct oropharyngeal bacterial taxa. Our findings highlight IgA as a potential driver of upper respiratory tract microbiota homeostasis.

Background: Allergic reactions to blood products are well recognised adverse events. The management of these is the same as for any allergen/s. The Serious Transfusion Incident Reporting (STIR) system focuses on serious reactions rather than minor reactions. Aim(s): To report on the clinical management/investigations of allergic reactions to blood products. Method(s): STIR receives acute event notifications via an online form, triggering a reaction-specific detailed investigation form sent for completion. Severity, treatment at time of reaction and subsequent investigations were analysed against recommendations. Result(s): From July 2012 - June 2018, STIR received 149 reports of allergic/ anaphylactic reactions; 46% of all acute reactions. Reaction severity was validated by expert review and determined to be mild (27%), moderate/ severe (56%), or anaphylactic/anaphylactoid (17%). Reactions related to platelets (69, 46%), FFP (fresh frozen plasma) (51, 34%), RBC (red blood cells) (29, 19%), other (9, 6%). Allergy is a clinical diagnosis; however some investigations will assist in determining likelihood or cause. Although IgA testing is recommended in severe/anaphylactic reactions only 24% were tested. Conclusion(s): Allergic reactions, contingent on the plasma content of blood products are a frequent source of reportable adverse events. Adherence to recommended management and investigation is inconsistent and highlights opportunities to improve knowledge for clinicians. (Table Presented) .

Background: There is no histological classification to predict disease flare in children with IgA nephropathy (IgAN). As macrophage (MQ) accumulation correlates with histological injury, we investigated new histological criteria to predict disease flare in pediatric IgAN. Method(s): A total of 73 children with biopsy proven IgAN underwent 2 years of steroid treatment followed by a protocol biopsy and then steroid tapering. The non-flare group successfully discontinued steroid treatment (N=61, 20.1+/-9.2 years at biopsy); the flare group exhibited increased proteinuria during the taper or cessation of treatment (N=12, 11.6+/-2.3 years at biopsy, p<0.05). Histological findings were evaluated using Oxford classification. Macrophage number and phenotype was assessed by immunofluorescence. Result(s): At first (diagnostic) biopsy, urine findings were comparable between the two groups, but the flare group had a higher serum IgA level (279+/-83 vs 214+/-87 mg/dL; P<0.05). Biopsies revealed no difference in mesangial proliferation (M), endocapillary proliferation (E), glomerulosclerosis (S), tubulointerstitial fibrosis (T), and crescent formation (C); however, the flare group had more total MQ (CD68+ cells) (p<0.05) and M1 MQ (CD68+CD86+ cells) (p<0.05). In addition, M1 MQ correlated with glomerular M, E, S, C lesions (all P<0.01). At second (protocol) biopsy, the flare group had more severe S (p<0.01) and T (p<0.05) lesions, and more glomerular and interstitial M2 MQ (CD68+CD163+ cells) (both p<0.01 vs non-flare group). In addition, M2 MQ correlated with S and T lesions (both p<0.001). ROC analyses revealed glomerular MQ number >2.2 cells at first biopsy could predict disease flare by sensitivity of 83%. Conclusion(s): MQ accumulation is a potential marker to predict disease flare in pediatric IgAN. The number of glomerular M1 MQ in active lesions at the first biopsy was related to flare occurrence, while glomerular and interstitial accumulation of M2 MQ in chronic lesions

Introduction: Henoch Schönlein purpura (HSP) is the most common type of vasculitis in childhood. HSP affects small blood vessels, and it rarely leads to serious complications such as bullous small vessel vasculitis, as it occurred in the case presented here.Case presentation: 5-year-old male who was brought to a primary healthcare center due to having arthralgia and purple skin lesions on his lower limbs. After the patient was diagnosed with HSP, he developed bullous lesions, so he was hospitalized and analgesic and topical management was started. During his hospital stay, the patient’s renal function was monitored, and since he did not experience other complications, he was discharged.Conclusion: The available literature on HSP suggests that its cutaneous bullous manifestation rarely occurs in pediatric population and that, unlike normal HSP cases, it is not always associated with renal and/or gastrointestinal involvement. However, regardless of the dermatological severity of this type of vasculitis, the function of the gastrointestinal and renal systems must be always monitored in these patients., Introducción. La púrpura Henoch-Schönlein (PHS) es la forma más común de vasculitis en la infancia; esta se da en pequeños vasos sanguíneos y no es frecuente que genere complicaciones graves como la vasculitis bullosa, tal como sucedió en el caso que se presenta a continuación.Presentación del caso. Paciente masculino de cinco años que fue traído a un centro de atención primaria con un cuadro clínico consistente en artralgias y aparición de lesiones purpúricas en miembros inferiores. Luego de ser diagnosticado con PHS, presentó lesiones bullosas, por lo que fue hospitalizado y se inició manejo analgésico y tópico; durante su estadía en el hospital se vigiló su función renal y, ya que no presentó otras complicaciones, se dio de alta.Conclusión. Las publicaciones disponibles sobre PHS sugieren que su presentación cutánea bullosa en pediatría no es frecuente y que no siempre se relaciona con un compromiso renal y/o gastrointestinal como la variante clásica; sin embargo, siempre debe vigilarse la función de estos sistemas sin importar la gravedad dérmica de esta vasculitis.

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

The fungus Candida albicans colonizes the oral mucosal surface of 30-70% of healthy individuals. Due to local or systemic immunosuppression, this commensal fungus is able to proliferate resulting in oral disease, called oropharyngeal candidiasis (OPC). However, in healthy individuals C. albicans causes no harm. Unlike humans mice do not host C. albicans in their mycobiome. Thus, oral fungal challenge generates an acute immune response in a naive host. Therefore, we utilized C. albicans clinical isolates which are able to persist in the oral cavity without causing disease to analyze adaptive responses to oral fungal commensalism. We performed RNA sequencing to determine the transcriptional host response landscape during C. albicans colonization. Pathway analysis revealed an upregulation of adaptive host responses due to C. albicans oral persistence, including the upregulation of the immune network for IgA production. Fungal colonization increased cross-specific IgA levels in the saliva and the tongue, and IgA+ cells migrated to foci of fungal colonization. Binding of IgA prevented fungal epithelial adhesion and invasion resulting in a dampened proinflammatory epithelial response. Besides CD19+ CD138- B cells, plasmablasts, and plasma cells were enriched in the tongue of mice colonized with C. albicans suggesting a potential role of B lymphocytes during oral fungal colonization. B cell deficiency increased the oral fungal load without causing severe OPC. Thus, in the oral cavity B lymphocytes contribute to control commensal C. albicans carriage by secreting IgA at foci of colonization thereby preventing fungal dysbiosis.

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody-based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.