Immunoglobulin A Concentration Research Articles

Effect of alterations in whole-body cryotherapy (WBC) exposure on post-match recovery markers in elite Premier League soccer players.

The use of whole-body cryotherapy (WBC) as a recovery intervention is prevalent amongst elite soccer players. However, there is a distinct lack of data available around chronic WBC use and post-match recovery markers in elite soccer. The aim of this study was to investigate the impact of different levels of WBC exposure on subjective and objective measures of post-match recovery in elite soccer players during a chronic exposure period. Sixteen male senior professional outfield soccer players participated in this study over two seasons. K means cluster analysis was used to classify low (-114 ± 2°C for 133 ± 2 s), medium (-121 ± 1°C for 173 ± 2 s) and high (-133 ± 1°C for 181 ± 2 s) cryotherapy exposure indexes (CEI). Salivary markers (immunoglobulin A (IgA) and alpha amylase (AA)) and subjective wellness scores (perceived fatigue, sleep quality, general muscle soreness and stress) were collected post-match across both seasons. Training load (session-RPE) was collected and used as a covariate to control for the load amongst groups. No differences were seen in perceived measures of wellness and salivary AA. Significantly lower IgA concentrations were observed in the medium CEI group (255 ± 32 µg∙ml-1) compared to the low (328 ± 38 µg∙ml-1) and high (306 ± 32 µg∙ml-1) groups. Therefore, increasing the level of chronic WBC exposure appears to have no additional benefit on subjective recovery and alpha amylase response post-match. However, there appears to be an optimal chronic WBC dose with regards to IgA response.

Secretory immunoglobulin A in preterm infants: determination of normal values in breast milk and stool.

IgA and its secretory form sIgA impact protection from infection and necrotising enterocolitis but little is known about quantities in preterm mums own milk (MOM) or infant stool, onset of endogenous production in the preterm gut, and what affects these. We measured by ELISA in MOM and stool from healthy preterm infants total IgA and sIgA longitudinally and additionally in MOM fresh, refrigerated, frozen, and after traversing feeding systems. In 42 MOM (median gestation 26 weeks), we showed total IgA levels and sIgA were highest in colostrum, fell over 3 weeks, and were not impacted by gestation. Median IgA values matched previous term studies (700 mcg/ml). In MOM recipients stool IgA was detected in the first week, at around 30% of MOM quantities. Formula fed infants did not have detectable stool IgA until the third week. Levels of IgA and sIgA were approximately halved by handling processes. MOM in the 3 weeks after preterm delivery contains the highest concentrations of IgA and sIgA. Endogenous production after preterm birth occurs from the 3 week meaning preterm infants are dependent on MOM for IgA which should be optimised. Routine NICU practices halve the amount available to the infant. (Secretory) Immunoglobulin A (IgA) is present in colostrum of maternal milk from infants as preterm as 23-24 weeks gestational age, falling over the first 3 weeks to steady levels similar to term. Gestation at birth does not impact (secretory) IgA levels in breast milk. IgA is present in very preterm infant stools from maternal milk fed infants from the first week of life, but not in formula milk fed preterm infants until week three, suggesting endogenous production from this point. Refrigeration, freezing, and feeding via plastic tubing approximately halved the amount of IgA available.

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease.

We previously observed that inflammatory bowel disease (IBD) may compromise oral host defense, as assessed by decreased salivary levels of immunoglobulin A (IgA) and myeloperoxidase (MPO). Biologic therapy with inhibitors of cytokines or adhesion molecules is increasingly used for patients with IBD. Little is known, however, about how this treatment modality affects the release and properties of saliva. Here, we aimed to determine how biologic therapy in patients who had not responded to previous standard treatment with conventional drugs affected the salivary concentration of IgA and MPO. To this end, unstimulated whole mixed saliva was collected before treatment or after 10–12 weeks of therapy from 27 patients with Crohn’s disease (CD) and 24 patients with ulcerative colitis (UC). After the induction phase of therapy with biologics, salivary levels of IgA and MPO increased significantly in UC, but not in CD patients. These increases were approximately 8-fold and 6-fold, for IgA and MPO, respectively. Moreover, these effects occurred in UC patients who responded successfully to therapy, but not in those who failed to improve. Furthermore, the relative increases in salivary IgA and MPO correlated with the relative decrease in UC severity, as assessed by the Mayo scale. These data indicate that the successful therapy with biologics in UC patients results also in improved oral host defense. However, it remains to be determined why such an effect does not occur during therapy for CD.

Local Heat Treatment of Goat Udders Influences Innate Immune Functions in Mammary Glands.

Heat stress and mastitis adversely affect milk production in dairy ruminants. Although the udder temperature is elevated in both conditions, the influence of this local temperature rise on milk production and immune function of ruminant mammary glands remains unclear. To address this question, we heated the mammary glands of goats by covering one half of the udder with a disposable heating pad for 24h, the other uncovered half served as a control. Sixteen Tokara goats (1-5 parity) and three Shiba goats (1-2 parity) at the mid-lactation stage were individually housed, fed 0.6kg of hay cubes and 0.2kg of barley per day, and had free access to water and trace-mineralized salt blocks. Milk samples were collected every 6h for 24h after covering (n = 16), and deep mammary gland tissue areas were collected after 24h (n = 5). The concentrations of antimicrobial components [lactoferrin, β-defensin-1, cathelicidin-2, cathelicidin-7, and immunoglobulin A (IgA)] in milk were measured by the enzyme-linked immunosorbent assay (ELISA). The localization of IgA was examined by immunohistochemistry. The mRNA expression and protein concentrations of C-C motif chemokine ligand-28 (CCL-28) and interleukin (IL)-8 in the mammary gland tissue were measured using quantitative polymerase chain reaction and ELISA, respectively. The somatic cell count in milk was significantly higher in the local heat-treatment group than in the control group after 12h of treatment. The treatment group had significantly higher concentrations of cathelicidin-2 and IgA than the control group after 24h of treatment. In addition, the number of IgA-positive cells in the mammary stromal region and the concentration of CCL-28 in the mammary glands were increased by local heat treatment. In conclusion, a local rise in udder temperature enhanced the innate immune function in mammary glands by increasing antimicrobial components.

Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi.

BackgroundRotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. While plasma rotavirus (RV)-specific IgA appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants.MethodsIn a case-control study we recruited infants presenting with severe rotavirus gastroenteritis following monovalent oral rotavirus vaccination (RV1 vaccine failures). Conditional logistic regression was used to determine the odds of rotavirus seronegativity (RV-specific IgA<20 U/mL) in these cases compared 1:1 with age-matched, vaccinated, asymptomatic community controls. Plasma RV-specific IgA was determined by ELISA for all participants at recruitment, and for cases at 10 days post symptom onset. Rotavirus infection and genotype were determined by antigen testing and RT-PCR respectively.ResultsIn 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: OR 3.1 (95%CI 1.6-5.9), p=0.001. In 60 infants with convalescent serology, 42/45 (93%, 95%CI 81-98%) infants seronegative at baseline became seropositive. Median rise in RV-specific IgA concentration following acute infection was 112.8 (IQR 19.1-380.6) fold.ConclusionsIn this vaccinated population with high residual burden of rotavirus disease, RV1 vaccine failure was associated with lower RV-specific IgA, providing further evidence of RV-specific IgA as a marker of protection. Robust convalescent RV-specific IgA response in vaccine failures suggests differences in wild-type and vaccine-induced immunity, which informs future vaccine development.

KDP, a Lactobacilli Product from Kimchi, Enhances Mucosal Immunity by Increasing Secretory IgA in Mice and Exhibits Antimicrobial Activity.

The potential of KDP, a lactic acid bacterial strain of Lactobacillus sakei, to enhance the production of mucosal specific immunoglobulin A (IgA) in mice and thereby enhance gut mucosal immunity was examined. KDP is composed of dead cells isolated from the Korean traditional food kimchi. Female BALB/c mice orally received 0.25 mg KDP once daily for 5 weeks and were co-administrated ovalbumin (OVA) for negative control and cholera toxin for positive control. Mice administered KDP exhibited increased secretory IgA (sIgA) contents in the small intestine, Peyer’s patches, serum, colon, and lungs as examined by ELISA. KDP also significantly increased the gene expression of Bcl-6, IL-10, IL-12p40, IL-21, and STAT4. In addition, KDP acted as a potent antioxidant, as indicated by its significant inhibitory effects in the range of 16.5–59.4% for DPPH, nitric oxide, maximum total antioxidant capacity, and maximum reducing power. Finally, KDP exhibited potent antimicrobial activity as evidenced by a significant decrease in the growth of 7 samples of gram-negative and gram-positive bacteria and Candida albicans. KDP’s adjuvant effect is shown to be comparable to that of cholera toxin. We conclude that KDP can significantly enhance the intestine’s secretory immunity to OVA, as well as act as a potent antioxidant and antimicrobial agent. These results suggest that orally administered KDP should be studied in clinical trials for antigen-specific IgA production.

Behavioural diversity as a potential welfare indicator for professionally managed chimpanzees (Pan troglodytes): Exploring variations in calculating diversity using species-specific behaviours

AbstractBehavioural diversity may serve as a positive indicator of animal welfare that can be applied in long-term monitoring schemes in managed settings (eg zoos, laboratories, farms). Behavioural diversity is often higher when animals live in stimulating environments and experience positive events. Unfortunately, welfare researchers have not adopted consistent, standardised approaches to measuring behavioural diversity. The goal of this exploratory study was to utilise data from 41 adult chimpanzees (Pan troglodytes) housed across 16 zoological institutions to examine various models of Shannon's Diversity Index. Specifically, we investigated the impact of: combining versus splitting behaviours, including only positive behaviours, including human interaction, and considering recipient behaviours. We evaluate how the inclusion or exclusion of different behaviours impacts the relationship of behavioural diversity with: (i) concentrations of faecal glucocorticoid metabolites (GCM), a common indicator of adrenal activity; (ii) concentrations of immunoglobulin-A (IgA), an indicator of immune function and potential indicator of positive welfare; and (iii) stereotypic behaviour, a validated indicator of poor welfare. Most indices had significant negative relationships with faecal GCM. Animals that express a variety of behaviours from their species-typical repertoire have lower average faecal GCM concentrations and are likely experiencing better welfare. We did not find significant relationships between the behavioural diversity indices and IgA concentrations. Two indices were inversely associated with stereotypic behaviour. Our findings provide additional support for using Shannon's Diversity Index to calculate behavioural diversity as a robust, valid measure of positive welfare. However, future publications must justify the process for including or excluding behaviours from calculations.

Effects of Pre/Probiotic Supplementation on Breast Milk Levels of TGF-b1, TGF-b2, and IgA: A Systematic Review and Meta-Analysis of Randomized-Controlled Trial.

Background: Previous studies have proposed that the maternal intake of pre/probiotics may affect the immune composition of breast milk. Nevertheless, the available findings are contradictory. This meta-analysis aimed to examine the impact of maternal supplementation with pre/probiotics on the levels of total immunoglobulin A (IgA), secretory IgA (SIgA), transforming growth factor beta 1 (TGF-β1), and TGF-2 in breast milk. Methods: PubMed and Scopus were systematically searched using a comprehensive search strategy for eligible randomized-controlled trials published up to February 2021. A random-effects model was applied to pool weighted mean difference and 95% confidence interval (CI) as effect size. Cochran's Q statistic and the I2 statistic were used to measure the between-study variance. Egger's regression test was used to assess publication bias. Results: A total of 12 different studies, with a total sample size of 1722 individuals (probiotic group: 858, placebo group: 864), were included in this meta-analysis. In the overall analysis, compared with placebo, maternal supplementation with pre/probiotics had no significant effect on concentrations of total IgA, SIgA, TGF-β1, and TGF-β2 in the breast milk. In the subgroup analysis, pre/probiotics did not affect total IgA, TGF-β1, and TGF-β2 in both colostrum/transitional and mature milk. However, a significant increase in SIgA was found in colostrum/transitional milk following pre/probiotic administration (WMD = 19.33, 95% CI: 0.83-37.83; p = 0.04), without evidence for remarkable heterogeneity (I2 = 0.0, p = 0.57). Conclusions: Maternal supplementation with pre/probiotics may increase SIgA in colostrum/transitional milk, without any effect on total IgA, TGF-β1, and TGF-β2.

The involvement of vitamin A in the production of secretory IgA in the respiratory epithelium for potential protection against SARS-CoV-2 infection

SARS-CoV-2 continues to infect thousands of people around the world. It has been established that the main transmission mechanism of this virus is via airborne route, which is why it initially infects the respiratory tract. Currently, the effectiveness of medications used against COVID-19 is limited, and although immunization programs have been initiated, there is international inequality in the distribution of vaccines. Accordingly, the search for adjuvant therapies continues to be an alternative for research. Supplementation with vitamin A has been associated to the decrease of mortality from infection; this effect could be mediated by retinoic acid (RA), which is the active metabolite of vitamin A that exerts immunomodulatory functions. According to preclinical studies, RA favors the production of secretory immunoglobulin A (IgA) in the respiratory tract. In addition to this, the retinol-binding protein has been correlated with the concentration of IgA and neutralizing antibodies in patients with influenza. Therefore, this review aims to address the involvement of vitamin A in the production of secretory IgA in the respiratory epithelium in order to highlight its potential protection against SARS-CoV-2 infection.

Stimulated saliva composition in patients with cancer of the head and neck region

BackgroundTo analyse over time changes in stimulated whole saliva regarding total protein, Immunoglobulin A (IgA), and mucin type O-glycans (mostly MUC5B and MUC7) in head and neck cancer patients.Methods29 dentate patients (20 men and 9 women, 59 ± 8 years) treated with curative radiation therapy and chemotherapy for cancer of the head and neck region were included. The stimulated whole salivary secretion rate was determined and saliva collected at four time-points: at pretreatment, and at 6 months, 1 and 2 years post treatment. The total protein concentration was determined spectrophotometrically by using Bicinchoninic Acid assay and Immunoglobulin A (IgA) by using ELISA technique. Glycosylation pattern of salivary mucins was determined in samples collected pre- and post treatment by using LC/MS electrospray and mucin content quantified using SDS-AgPAGE gels and PAS staining.ResultsCompared with pretreatment, the total protein concentration was increased already at 6 months post treatment (p < 0.01), and continued to increase up to 2 years post treatment (p < 0.001). During that period no significant changes in IgA concentration was detected. At pretreatment, the output/min of both total protein and IgA was significantly higher than at all time-points post treatment. Saliva from the cancer patients showed a low abundance/no detectable MUC7, while the MUC5B level remained, compared to saliva from a healthy control. The glycomic analysis showed that the percentage of core 2 O-glycans was increased as core 1, 3 and 4 O-glycans were decreased. The level of sialylation was higher at 6 months post treatment, while sulfation was lower.ConclusionA decreased output per minute of proteins at decreased salivary secretion rate, as well as reduced sulfation of MUC5B at 6 months post treatment tended to correlate with the patients’ experience of sticky saliva and oral dryness. At 2 years post treatment, the decreased amount of IgA combined with a lowered salivary secretion rate indicate a reduced oral defense with increased risk of oral infections.

DESPITE THEIR UTILITY IN IDIOPATHIC PULMONARY FIBROSIS, SERUM IGA AND MONOCYTE COUNT ARE NOT PREDICTIVE OF BASELINE PULMONARY FUNCTION, MORTALITY, OR INTERSTITIAL LUNG DISEASE PATTERN IN RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that confers a poor prognosis. Previously, immunoglobulin A (IgA) level has been used as a surrogate marker of transforming growth factor (TGF)-beta, an important mediator of pulmonary fibrosis, and increased IgA level was associated with worse outcomes in IPF [1]. Recent studies have also described associations between serum monocyte count and clinical outcomes in IPF [2]. Rheumatoid arthritis related interstitial lung disease (RA-ILD) has many similarities with IPF, including similar genetic risk, survival, and ILD pattern. We hypothesized that elevated IgA and monocyte count would correlate with clinical outcomes and ILD patterns in RA-ILD. METHODS: We performed a single-center, retrospective chart review of patients diagnosed with RA-ILD between 2010 and 2021 using an ICD9 and ICD10 based search. Of 256 patients who met our search criteria, 77 were included in the final analysis. Patients were included if they had serum IgA and monocyte count in the chart, a confirmed diagnosis of RA based on ACR/EULAR criteria, and ILD based on chart diagnosis and confirmatory imaging. Patients were excluded if they received rituximab prior to their blood draw. High resolution computed tomography images closest to the date of the blood draw were analyzed by consensus reads by two blinded thoracic radiologists using the 2018 ATS/ERS/JRS/ALAT guidelines. IgA level and monocyte count were compared to pulmonary function at time of blood draw, time to death or lung transplant, UIP pattern as well as sex, ethnicity and age. RESULTS: The mean and median IgA levels were 342.8 mg/dl and 329.0 mg/dl, respectively. There was no statistically significant association between IgA level and the UIP pattern (p = 0.689). IgA level was not associated with baseline FVC% predicted or baseline DLCO% predicted (p = 0.218 and p = 0.639). The effect of IgA level on overall survival is not significant in the simple Cox regression model [hazard ratio (HR) = 1.002, 95% confidence interval (CI) 0.999-1.004, p = 0.203].The mean and median absolute monocyte counts were 6.5×108 cells/liter and 6.0×108 cells/liter, respectively. There was no association between monocyte count and the UIP pattern (p = 0.762). Monocyte count was not associated baseline with FVC% predicted (p = 0.963) or baseline DLCO% predicted (p = 0.882). The effect of monocyte count on overall survival is not significant in the simple Cox regression model (HR = 1.099, 95% CI 0.449-2.690, p = 0.836). CONCLUSIONS: Serum IgA and monocyte concentration were not associated with important clinical outcomes in this RA-ILD cohort. This was a retrospective analysis, it may be that prospective, longitudinal analysis of IgA and monocyte count in RA-ILD could yield different results. CLINICAL IMPLICATIONS: N/A DISCLOSURES: No relevant relationships by Joe Johnstone, source=Web Response Consultant relationship with Boehringer Ingelheim Please note: $1001 - $5000 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Genentech Please note: $1001 - $5000 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Celgene Please note: $1001 - $5000 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Galapagos Please note: $1001 - $5000 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Eleven P15 Please note: $1001 - $5000 by Joyce Lee, source=Web Response, value=Consulting fee No relevant relationships by Scott Matson, source=Web Response No relevant relationships by Sahil Pandya, source=Web Response No relevant relationships by Kristen Pope, source=Web Response No relevant relationships by Xiaosong Shi, source=Web Response No relevant relationships by Christopher Walker, source=Web Response

Genomic association and further characterisation of faecal immunoglobulin A deficiency in German Shepherd dogs.

BackgroundImmunoglobulin A (IgA) deficiency, chronic enteropathies and exocrine pancreatic insufficiency (EPI) have a high prevalence in German Shepherd dogs (GSD). This prospective study determined the prevalence of faecal IgA deficiency (IgAD) in GSD and investigated several candidate genes and the canine genome for a region or locus co‐segregating with IgAD in GSD. Faecal IgA concentrations were quantified and genomic DNA was extracted from 8 GSD with an undetectable faecal IgA (classified as IgAD) and 80 non‐IgAD GSD. The canine minimal screening set II microsatellite markers were genotyped, with evidence of an association at p < 1.0 × 10−3. Faecal IgA concentrations were also tested for an association with patient clinical and biochemical variables.ResultsAllele frequencies observed using the candidate gene approach were not associated with faecal IgAD in GSD. In the genome‐wide association study (GWAS), the microsatellite marker FH2361 on canine chromosome 33 approached statistical significance for a link with IgAD in GSD (p = 1.2 × 10−3). A subsequent GWAS in 11 GSD with EPI and 80 control GSD revealed a significant association between EPI and FH2361 (p = 8.2 × 10−4).ConclusionsThe lack of an association with the phenotype of faecal IgAD in GSD using the candidate gene approach and GWAS might suggests that faecal IgAD in GSD is a relative or transient state of deficiency. However, the prevalence of faecal IgAD in GSD appears to be low (<3%). The relationship between faecal IgAD, EPI and loci close to FH2361 on canine chromosome 33 in GSD warrants further investigation.

The Enhancement of Intestinal Immunity in Offspring Piglets by Maternal Probiotic or Synbiotic Supplementation Is Associated With the Alteration of Gut Microbiota.

A total of 64 pregnant Bama mini-pigs were used to investigate the effects of maternal probiotic or synbiotic supplementation during gestation and lactation on immune response, intestinal morphology, and microbiota community of offspring piglets. The sows were assigned randomly to one of four groups, control group (basal diet), antibiotic group (basal diet supplemented with 50 g/t virginiamycin), probiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig), or synbiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig + 500 g/t xylo-oligosaccharides) during pregnancy and lactation periods. After weaning, two piglets close to the average body weight (BW) per litter were selected and fed a basal diet. Eight piglets with similar BW were selected from each group for sample collection at 65 d-old. The results showed that plasma interleukin (IL)-2 and lipopolysaccharide concentrations were decreased (P < 0.05) in the probiotic group, while the immunoglobulin A (IgA) concentration in the probiotic and synbiotic groups was increased (P < 0.05), when compared with the control group. The jejunal IL-10, interferon-α, and secretory IgA (sIgA) concentrations were increased (P < 0.05) in the probiotic and synbiotic groups, as well as the ileal sIgA concentration in the probiotic group. The jejunal villus height (VH) and the ratio of VH to crypt depth were increased (P < 0.05) in the probiotic group, as well as the ileal VH in the synbiotic group. Furthermore, the piglets from the antibiotic group exhibited a lower microbiota diversity in the jejunum and ileum. The piglets from the synbiotic group had higher relative abundances of Actinobacteria, Bifidobacterium, Turicibacter, and Clostridium in the jejunum compared with the antibiotic group. Dietary probiotic treatment increased (P < 0.05) the relative abundance of Psychrobacter in the ileum compared with the antibiotic and control groups. Spearman's correlation analysis revealed that the relative abundances of Bifidobacterium, Clostridium, and Blautia in the jejunum and Psychrobacter in the ileum, were positively correlated with the alterations of immunoglobulin and cytokines. Collectively, these findings suggest that maternal interventions with probiotic or synbiotic are promising strategies for improving the immune response of offspring piglets by altering the gut microbiota.

Assessment of Age-Related Changes of Salivary Immunoglobulin A Levels among Healthy Individuals.

Background:Secretory immunoglobulin A (IgA) is the first line of defense against pathogens that invade mucosal surfaces. It has been reported that the immune system exhibits profound age-related changes. The aim of this study was to investigate the age-dependent changes of salivary IgA among healthy individuals.Materials and Methods:Saliva samples were collected from 120 healthy individuals (aged 11–70 years). The salivary IgA concentrations were measured by the use of a single radial immunodiffusion technique and analyzed using the Mann–Whitney U, Kruskal–Wallis, and Chi-square tests.Results:The mean salivary IgA levels were 81.11 ± 4.50 mg/dl at age 11–20 years, 92.71 ± 13.76 mg/dl at age 21–30 years, 96.50 ± 4.04 mg/dl at age 31–40 years, 104.96 ± 10.15 mg/dl at age 41–50 years, 113.22 ± 7.85 mg/dl at age 51–60 years, and 91.38 ± 4.77 mg/dl at age 61–70 years. There was a significant difference among the mean salivary IgA levels of different age groups (P < 0.001).Conclusion:These results showed that the salivary IgA levels exhibit age-related changes. Oral immunization may be considered to improve oral immunity when the salivary concentrations of IgA begin to decrease during lifetime.

The Alteration of Salivary Immunoglobulin A in Autism Spectrum Disorders.

Objectives: Autism spectrum disorders (ASD) are neurodevelopmental disorders with changes in the gut and oral microbiota. Based on the intimate relationship between the oral microbiota and oral mucosal immunity, this study aimed to investigate changes in salivary immunoglobulin A (IgA) level in ASD and the underlying mechanism for any such changes.Methods: We recruited 36 children diagnosed with ASD and 35 normally developing children and measured their salivary IgA content using enzyme-linked immunosorbent assay (ELISA). The valproate (VPA) -treated ASD mouse model was established by prenatal exposure to valproate and mouse salivary IgA content was also quantified by ELISA. The submandibular glands of VPA and control mice were isolated and analyzed using qRT-PCR, immunofluorescence staining, and flow cytometry. ASD-related Streptococci were co-incubated with the human salivary gland (HSG) cell line, and western blotting was used to detect the levels of relevant proteins.Results: We found that salivary IgA content was significantly decreased in patients with ASD and had a significant ASD diagnostic value. The salivary IgA content also decreased in VPA mice and was significantly correlated with autistic-like behaviors among them. The mRNA and protein levels of the polymeric immunoglobulin receptor (Pigr) were downregulated in the submandibular glands of VPA mice and the Pigr mRNA level was positively correlated with mouse salivary IgA content. HSG cells treated with ASD-related Streptococci had reduced PIGR protein level.Conclusion: Therefore, protective IgA levels were reduced in the saliva of individuals with ASD, which correlated with the bacteria-induced downregulation of Pigr in salivary glands. This study suggests a new direction for ASD diagnosis and prevention of oral diseases in ASD cohorts and provides evidence for the ASD mucosal immunophenotype in the oral cavity.

Whole tissue homogenization preferable to mucosal scraping in determining the temporal profile of segmented filamentous bacteria in the ileum of weanling rats.

Segmented filamentous bacteria (SFB) are thought to play a role in small intestine immunological maturation. Studies in weanling mice have shown a positive correlation between ileal SFB abundance and plasma and faecal interleukin 17 (IL-17) and immunoglobulin A (IgA) concentrations. Although the first observation of SFB presence was reported in rats, most studies use mice. The size of the mouse ileum is a limitation whereas the rat could be a suitable alternative for sufficient samples. Changes in SFB abundance over time in rats were hypothesized to follow the pattern reported in mice and infants. We characterized the profile of SFB colonization in the ileum tissue and contents and its correlation with two immune markers of gastrointestinal tract (GIT) maturation. We also compared two published ileum collection techniques to determine which yields data on SFB abundance with least variability. Whole ileal tissue and ileal mucosal scrapings were collected from 20- to 32-day-old Sprague-Dawley rats. SFB abundance was quantified from proximal, middle and distal ileal tissues, contents and faeces by quantitative PCR using SFB-specific primers. Antibody-specific ELISAs were used to determine IL-17 and IgA concentrations. Significant differences in SFB abundance were observed from whole and scraped tissues peaking at day 22. Variability in whole ileum data was less, favouring it as a better collection technique. A similar pattern of SFB abundance was observed in ileum contents and faeces peaking at day 24, suggesting faeces can be a proxy for ileal SFB abundance. SFB abundance at day 26 was higher in females than males across all samples. There were significant differences in IgA concentration between days 20, 30 and 32 and none in IL-17 concentration, which was different from reports in mice and infants.

Effects of the intake of non-live Bifidobacterium bifidum on the faecal IgA of full-term infants: a double-blind, randomised, placebo-controlled study.

Bifidobacterium bifidum OLB6378 (OLB6378) was selected as a strain that enhances the production of secretory immunoglobulin A (IgA) in vitro. This ability of non-live OLB6378 has been shown by a clinical trial in preterm infants. In the present study, we examined whether non-live OLB6378 also enhances the production of secretory IgA, even in full-term infants. One hundred full-term infants were allocated to receive formula with (BbF group, 49 infants) or without non-live OLB6378 (PF group, 51 infants). Breastfeeding was prioritised, so infant formula was used for infants with breastfeeding difficulties. The intervention was initiated by five days of age. The faecal IgA concentration and OLB6378 level were determined at one, two, four, and eight weeks of age. Faecal IgA in the BbF group (1.04 ± 0.47 mg/g of faeces, n=45) was significantly higher than that in the PF group (0.85 ± 0.42 mg/g of faeces, n=49) at four weeks of age (p=0.047). OLB6378 was not detected in faeces at any age. This indicated that production of secretory IgA in full-term infants may also be enhanced by non-live OLB6378 intake.

Virulence factor-related gut microbiota genes and immunoglobulin A levels as novel markers for machine learning-based classification of autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition for which early identification and intervention is crucial for optimum prognosis. Our previous work showed gut Immunoglobulin A (IgA) to be significantly elevated in the gut lumen of children with ASD compared to typically developing (TD) children. Gut microbiota variations have been reported in ASD, yet not much is known about virulence factor-related gut microbiota (VFGM) genes. Upon determining the VFGM genes distinguishing ASD from TD, this study is the first to utilize VFGM genes and IgA levels for a machine learning-based classification of ASD. Sequence comparisons were performed of metagenome datasets from children with ASD (n = 43) and TD children (n = 31) against genes in the virulence factor database. VFGM gene composition was associated with ASD phenotype. VFGM gene diversity was higher in children with ASD and positively correlated with IgA content. As Group B streptococcus (GBS) genes account for the highest proportion of 24 different VFGMs between ASD and TD and positively correlate with gut IgA, GBS genes were used in combination with IgA and VFGMs diversity to distinguish ASD from TD. Given that VFGM diversity, increases in IgA, and ASD-enriched VFGM genes were independent of sex and gastrointestinal symptoms, a classification method utilizing them will not pertain only to a specific subgroup of ASD. By introducing the classification value of VFGM genes and considering that VFs can be isolated in pregnant women and newborns, these findings provide a novel machine learning-based early risk identification method for ASD.

Dietary resistant starch preserved through mild extrusion of grain alters fecal microbiome metabolism of dietary macronutrients while increasing immunoglobulin A in the cat.

Dietary digestion-resistant starch (RS) provides health benefits to the host via gut microbiome-mediated metabolism. The degree to which cats manifest beneficial changes in response to RS intake was examined. Healthy cats (N = 36) were fed identically formulated foods processed under high (n = 17) or low (n = 19) shear extrusion conditions (low and high RS levels [LRS and HRS], respectively). Fecal samples collected after 3 and 6 weeks' feeding were assayed for stool firmness score, short-chain fatty acids, ammonia, and changes to the global metabolome and microbiome; fecal immunoglobulin A (IgA) was analyzed at week 6. Few differences were seen in proximate analyses of the foods; stool firmness scores did not differ. In cats consuming HRS food, concentrations of fecal butyrate and the straight chain:branched chain fatty acid ratio were significantly greater in feces at both weeks 3 and 6, while fecal ammonia was reduced at week 6 relative to feces from LRS-fed cats. Fecal IgA concentrations were significantly higher at week 6 with HRS food. RS consumption altered 47% of the fecal metabolome; RS-derived sugars and metabolites associated with greater gut health, including indoles and polyamines, increased in the cats consuming HRS food relative to those fed the LS food, while endocannabinoid N-acylethanolamines decreased. Consumption of HRS food increased concentrations of the ketone body 3-hydroxybutyrate in feces and elevated concentrations of reduced members of NADH-coupled redox congeners and NADH precursors. At the microbiome genus-level, 21% of operational taxonomic units were significantly different between food types; many involved taxa with known saccharolytic or proteolytic proclivities. Microbiome taxa richness and Shannon and Simpson alpha diversity were significantly higher in the HRS group at both weeks. These data show that feline consumption of grain-derived RS produces potentially beneficial shifts in microbiota-mediated metabolism and increases IgA production.

Macronutrient, immunoglobulin a and total antioxidant capacity profiles of human milk from 1 to 24\u2009months: a cross-sectional study in Thailand

BackgroundAn extended duration of breastfeeding of up to two years is encouraged by many health authorities, but information regarding the composition of milk after one year postpartum is limited. The goal of this study was to determine the association between the duration of lactation and macronutrient contents, immunoglobulin A (IgA) levels and total antioxidant capacity (TAC) in human milk (HM), from 1 to 24 months postpartum.MethodsCross-sectional milk samples were collected between January and April 2019 from mothers with healthy full-term children who had been lactating for 1 to 24 months. The HM was biochemically analyzed for protein and carbohydrate contents by colorimetric assays. The fat content was determined by capillary centrifugation, and the energy content was calculated from the results of centrifugation assays. IgA levels and TAC were determined by ELISA and a Trolox equivalent antioxidant capacity (TEAC) assay, respectively. Pearson’s correlation coefficient and Spearman’s rank correlation coefficient were used to determine associations between months of lactation and milk composition, and multiple regression analysis was used to assess associations between months of lactation and milk composition adjusted for relevant covariates. Differences were considered significant at p < 0.05.ResultsOne hundred eighty-four milk samples were analyzed. The month of lactation was positively associated with the fat concentration (B = 0.31, SE = 0.09, p = 0.001), energy content (B = 3.11, SE = 0.92, p = 0.001), and IgA (B = 4.17, SE = 1.08, p < 0.001) but negatively associated with the carbohydrate concentration (B = − 0.22, SE = 0.01, p = 0.04). No association was observed between the month of lactation and the protein concentration or TAC after adjustment for maternal age, maternal BMI, birth order, and breastfeeding frequency.ConclusionThe duration of lactation was found to be positively associated with the fat, energy, and IgA content in HM for up to two years postpartum, and negatively associated with carbohydrate concentration. More prospective cohort studies are needed to obtain evidence-based knowledge regarding the changes in HM composition throughout the course of lactation.