Effect Of IgA Research Articles

Innovative use of sensor technology to study grazing behaviour and its associations with parasitic resistance in sheep

Gastrointestinal nematodes (GINs) are a concern for sheep production and are associated with significant economic losses globally, driving the need for effective management strategies. The aims of this research were first to determine the influence of GIN infections on sheep grazing behaviours, specifically grazing time (GT) and grazing event length (GL), and then to estimate the genetic and phenotypic correlation between faecal egg counts (FEC) and salivary specific IgA activity vs GT and GL. Data were collected from 146 Merino sheep on a commercial farm in Victoria, Australia. Faecal, saliva and body weight (BW) were collected at four time points (A: Oct 2019, B: early May 2020, C: late May 2020, and D: Jul 2020), while tri-axial accelerometer sensors recorded GT and GL for the length of 26 days between B and C. Univariate linear regression and Bayesian Generalised Linear Mixed Model, estimated using Markov Chain Monte Carlo, were used to assess the relationships between the behaviours and infection indicators. We found an increase in the logarithm of FEC was associated with a significant rise in grazing time (p < 0.05), suggesting compensatory behaviour in infected sheep. GT also accounted for 6% of the FEC variation. In contrast, the effect of IgA on GT was not significant (p > 0.05). There was a positive genetic and phenotypic correlation estimated between GT and FEC, however, the High Posterior Density interval for the genetic and phenotypic correlations between GT and FEC indicates some uncertainty in these estimates. These results imply that sheep may modify their grazing strategies as an adaptive response to parasitic infections to ease the impact on their nutritional intake. This study improves our understanding of how natural GIN infections affect sheep behaviour and highlights the potential to use animal behaviours as a precision livestock farming tool and in breeding for resilience against parasites.

Adherent-invasive E. coli - induced specific IgA limits pathobiont localization to the epithelial niche in the gut.

Adherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn's disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive. Antibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium. Persistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC - epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice. These results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.

Immunoglobulin a suppresses B cell receptor-mediated activation of mouse B cells with differential inhibition of signaling molecules

Context We previously reported that monoclonal mouse immunoglobulin (Ig) A, OA-4, attenuates sensitization in mice by suppressing B cell activation. Objective Here, it is demonstrated for the first time that mouse IgA inhibits mouse B cell activation in vitro under natural conditions (i.e. in the absence of chemical, physical, and genetic modifications of IgA and B cells). Materials and methods Mouse splenocytes were stimulated with anti-B cell receptor (BCR) antibody or lipopolysaccharide (LPS) in the presence or absence of OA-4. Splenic B cell proliferation and the activation of several intracellular signaling molecules were measured. Results Anti-BCR antibody-induced proliferation was markedly inhibited by OA-4 or the commercially available mouse IgA S107, whereas LPS-induced proliferation was weakly attenuated by a high concentration of OA-4. Moreover, OA-4 markedly decreased the anti-BCR antibody-induced phosphorylation of p44/42 mitogen-activated protein kinase (ERK) and CD22 and decreased phosphorylated phospholipase (PLC) γ2 and intracellular Ca2+ levels moderately, whereas protein kinase B (Akt) phosphorylation was not affected by OA-4. The MAPK/ERK kinase-ERK and phosphoinositide 3-kinase-Akt pathways were found to play a role in the proliferation of splenocytes induced by anti-BCR antibody based on experiments with their inhibitors. In contrast to that in splenic B cells, ERK phosphorylation induced by anti-BCR antibody in A20 cells was not inhibited by OA-4. The modulatory effects of IgA were different among the cell types and signaling pathways. Conclusion IgA is a potential immunoregulatory drug utilizing new mechanisms that affect splenic B cells but not A20 lymphomas.

Longitudinal assessment of the bovine ocular bacterial community dynamics in calves

BackgroundInfectious Bovine Keratoconjunctivitis (IBK), commonly known as pinkeye, is one of the most significant diseases of beef cattle. As such, IBK costs the US beef industry at least 150 million annually. However, strategies to prevent IBK are limited, with most cases resulting in treatment with antibiotics once the disease has developed. Longitudinal studies evaluating establishment of the ocular microbiota may identify critical risk periods for IBK outbreaks or changes in the microbiota that may predispose animals to IBK.ResultsIn an attempt to characterize the establishment and colonization patterns of the bovine ocular microbiota, we conducted a longitudinal study consisting of 227 calves and evaluated the microbiota composition over time using amplicon sequence variants (ASVs) based on 16S rRNA sequencing data and culture-based approaches. Beef calves on trial consisted of both male (intact) and females. Breeds were composed of purebred Angus and composites with varying percentages of Simmental, Angus, and Red Angus breeds. Average age at the start of the trial was 65 days ±15.02 and all calves remained nursing on their dam until weaning (day 139 of the study). The trial consisted of 139 days with four sampling time points on day 0, 21, 41, and 139. The experimental population received three different vaccination treatments (autogenous, commercial (both inactivated bacteria), and adjuvant placebo), to assess the effectiveness of different vaccines for IBK prevention. A significant change in bacterial community composition was observed across time periods sampled compared to the baseline (p < 0.001). However, no treatment effect of vaccine was detected within the ocular bacterial community. The bacterial community composition with the greatest time span between sampling time periods (98d span) was most similar to the baseline sample collected, suggesting re-establishment of the ocular microbiota to baseline levels over time after perturbation. The effect of IgA levels on the microbial community was investigated in a subset of cattle within the study. However, no significant effect of IgA was observed. Significant changes in the ocular microbiota were identified when comparing communities pre- and post-clinical signs of IBK. Additionally, dynamic changes in opportunistic pathogens Moraxella spp. were observed and confirmed using culture based methods.ConclusionsOur results indicate that the bovine ocular microbiota is well represented by opportunistic pathogens such as Moraxella and Mycoplasma. Furthermore, this study characterizes the diversity of the ocular microbiota in calves and demonstrates the plasticity of the ocular microbiota to change. Additionally, we demonstrate the ocular microbiome in calves is similar between the eyes and the perturbation of one eye results in similar changes in the other eye. We also demonstrate the bovine ocular microbiota is slow to recover post perturbation and as a result provide opportunistic pathogens a chance to establish within the eye leading to IBK and other diseases. Characterizing the dynamic nature of the ocular microbiota provides novel opportunities to develop potential probiotic intervention to reduce IBK outbreaks in cattle.

SAT-456 Effect of FangjiHuangqi decoction on IL-6 and TGF-β1 secretion by HMC after intervention of inflammatory factors secreted by lymphocytes based on p38MAPK signaling pathway

Based on the previous experimental research, we designed the experiment to select inflammatory factors secreted by peripheral blood lymphocytes to co-incubate with human mesangial cells, and to explore the effects of Fangji Huangqi Decoction on IL-6, TGF-β1 and p38MAPK signaling pathways affecting IgA nephropathy. Human mesangial cells (HMC) were induced by inflammatory factors secreted by HPBL from healthy people and IgA nephropathy patients for 24 hours. The cells were divided into five groups: (1) Healthy blank group: HMC culture medium + 10% healthy control HPBL culture supernatant + 10% blank healthy human serum; (2) Healthy dosing group: HMC culture medium + 10% healthy control HPBL culture supernatant + 10% medicated serum; (3) IgA + blank serum: HMC culture medium + 10% IgA nephropathy HPBL culture supernatant + 10% blank healthy human serum; (4) IgA + medicated serum group: HMC culture medium + 10% IgA nephropathy HPBL culture supernatant + 10% IgA nephropathy patients HPBL culture supernatant IgA + blocker group: HMC culture medium + 10% IgA nephropathy patients HPBL culture supernatant + P38MAPK specific blocker SB203580 + 10% drug-containing serum. After 48 hours of culture, the expression of TGF-β1, IL-6 and p38 MAPK was detected by RT-PCR, Western Blot and immunofluorescence. The expression of IL-6, TGF-β1 and p38MAPK in IgA+blank serum group was significantly higher than that in healthy blank group (P<0.05). The expression of IL-6, TGF-β1 and p38MAPK in IgA+blank serum group was lower than that in IgA+blank serum group (P<0.05). There was no significant difference in the expression of IL-6, TGF-β1 and p38MAPK between IgA+blocker group and healthy group (P>0.05). The expression of IL-6, TGF-β1 and p38MAPK in the dosage group was lower than that in the IgA + blank serum group (P < 0.05). _The expression of IL-6, TGF-β1, p38 and p-p38 protein in IgA+containing serum group was lower than that in IgA+blank serum group (P < 0.05). There was no significant difference in the expression of IL-6, p38 and p-p38 protein between IgA+blocker group and healthy group (P > 0.05). The expression of IL-6, TGF-β1, p38 and p-p38 protein in IgA+blocker group was lower than that in IgA+blank serum group (P < 0.05). The results of epidemic fluorescence showed that the secretion of IL-6, TGF-β1 and p38 in IgA + blank serum group was higher than that in healthy blank serum group. The same effect of IgA + drug-containing serum group and IgA + blocker group could reduce the levels of IL-6, TGF-β1 and p38. The activation level of p38 MAPK in HMC induced by inflammatory factors secreted by peripheral blood lymphocyte in IgA nephropathy patients is significantly increased, and the secreted inflammatory factors IL-6 and TGF-β1 are also increased. Fangji Huangqi Decoction can significantly reduce the activation level, suggesting that the inhibition of p38 MAPK activation may also be one of the mechanisms of Fangji Huangqi Decoction in inhibiting the secretion of inflammatory factors by HMC. Fangji Huangqi Decoction can delay the progress of IgA nephropathy by reducing the activation of p38 MAPK, reducing the secretion of TGF-β1 and IL-6 by mesangial cells, and reducing the inflammatory reaction of mesangial cells.

Normas de reação para peso aos 365 e 550 dias de idade em bovinos Guzerá no Nordeste do Brasil

Objetivou-se avaliar o efeito da interação genótipo ambiente (IGA) sobre os pesos ajustados aos 365 (P365) e 550 (P550) dias de idade de bovinos Guzerá por meio de modelos hierárquicos Bayesianos de norma de reação. O banco de dados utilizado foi cedido pela Associação Brasileira dos Criadores de Zebu (ABCZ) e continha 15169 e 11183 registros para o P365 e P550, respectivamente. Ajustou-se um modelo animal (MA) e modelos hierárquicos de norma de reação com variâncias homogenias e heterogenias em um passo (MHNRHO1P e MHNRHE1P, respectivamente) e dois passos (MHNRHO2P e MHNRHE2P, respectivamente) para avaliar a existência e efeito da IGA. O MHNRHO1P foi o modelo de melhor ajuste. As estimativas de herdabilidade no MA foram de 0,37 e 0,29 para o P365 e P550, respectivamente. Foram obtidos valores de herdabilidade variando de 0,21 a 0,71 para o P365 e 0,06 a 0,93 para o P550 no MHNRHO1P ao longo do gradiente ambiental. As correlações de Spearman entre as classificações dos reprodutores para o P365 e P550 variaram de 0,26 a 0,99 e de -0,99 a 0,99, respectivamente, e as correlações genéticas variaram entre 0,70 a 1,00 e 0,40 a 1,00 para o P365 e P550, respectivamente. Existe IGA em bovinos da raça Guzerá no Nordeste do Brasil para o P365 e P550, sendo necessário considerar a possibilidade de inclusão deste efeito nas avaliações genéticas.

Evaluating the relationship between dental caries number and salivary level of IgA in adults.

BackgroundDental caries are the most common mouth infectious disease and also chronic disease of childhood. Saliva plays different roles in oral cavity; for example, salivary immunoglobulins play significant role in body and oral immunity. Various studies were conducted on the different effects of IgA on oral cavity, especially dental caries, and reported controversial results. The current study aimed to compare salivary IgA level at different stages of dental caries in adults.Material and MethodsA total of 40 adults, aged 20 to 40 years, referred to the department of oral medicine at Qazvin Faculty of Dentistry, were selected voluntarily based on the number of decayed teeth. Their unstimulated saliva was collected by the spitting method. The cases were assigned to 4 groups each of 10, based on the number of decayed teeth, as follows: Group 1: Caries free, Group 2: With 1 or 2 decayed teeth, Group 3: With 3 or 4 decayed teeth, and Group 4: With 5 or more decayed teeth. None of the cases had systemic diseases or the history of using medicines which affect the quality or quantity of saliva. The salivary IgA level of the cases was measured immunoturbidometrically and analyzed by ANOVA and t test.ResultsSignificant difference was observed between the groups 1 and 4, but there was no significant difference between the other groups.ConclusionsAccording to the results of the current study, the salivary IgA can be considered as an index for the function of immune system, which may be increased by the number of decayed teeth. In fact, the increase of salivary IgA is just the response of immune system to the accumulation of microorganisms and may be the attempt of body to control them. Key words:Saliva, IgA, Dental caries.

Therapeutic Potential of Monoclonal IgA Antibodies in Allergic Diseases: Suppressive Effect of IgA on Immune Responses Induced By Re-exposure to Antigen in Sensitized Mice by Monoclonal IgE Antibody That Binds to a Different Epitope of the Same Antigen

Repeated exposure to an allergen induces allergic symptoms by activating mast cells that express anti-allergen IgE, which results in further sensitization to an allergen. Considering that additional sensitization elicits more severe allergic reactions upon the next allergen challenge, suppression of the boosting phase represents an efficacious way to prevent and ameliorate allergic diseases. In this study, we investigated the therapeutic potential of allergen-specific monoclonal IgA on allergic diseases. This antibody acts by decreasing immune responses upon exposure to allergens in mice previously sensitized by a monoclonal IgE that recognizes the allergen. The lack of inhibitory effects of anti-ovalbumin monoclonal IgA (OA-4) on either the binding of anti-ovalbumin monoclonal IgE (OE-1) to ovalbumin by ELISA or on ovalbumin-induced degranulation of rat basophilic leukemia RBL2H3 cells sensitized with OE-1 indicated that OA-4 and OE-1 recognized different epitopes on ovalbumin. Immune responses (anti-ovalbumin IgG1 production and cytokine release from splenocytes) induced by intravenous ovalbumin challenge in DBA/1J mice passively sensitized with OE-1 were inhibited by intravenous injection of OA-4 15 min before challenge without affecting anaphylaxis. Moreover, OA-4 injection 1 h after ovalbumin challenge also effectively suppressed immune responses. The achievement of immunosuppression by IgA injection occurred even after allergen challenge in mice in an epitope-independent fashion. These findings suggest that monoclonal IgA administered at the time of hospitalization of a patient with allergic symptoms, who was already exposed to the allergen in the presence of IgE recognizing an undefined epitope(s) on the allergen, should effectively relieve allergic disease through its immunosuppressive effects.

IgA increases NF-kB in CALU-3 cells: Implications for cystic fibrosis airway inflammation

Rationale Cystic fibrosis (CF) airways are plagued by neutrophil-predominant inflammation and infection. CF epithelial cells have increased activity of the pro-inflammatory transcription factor, NF-κB, resulting in increased production of the neutrophil chemotactic factor, IL-8. IgA is an important protein that helps protect the airway epithelium from attachment by infectious pathogens, and is found in increased concentrations in CF serum and sputum. We asked whether IgA itself might contribute to the pro-inflammatory process by increasing NF-κB activity and therefore IL-8 production in CALU-3 airway epithelial cells that endogenously express both the CFTR (wild-type) and the receptor for IgA, the polymeric immunoglobulin receptor (pIgR). Methods CALU-3 cells were stimulated with buffer or pIgA, and processed for DNA binding activity of NF-κB (p65 subunit) by electromobility gel shift assay (EMSA). Increased NF-κB activity was also assessed by western blotting for the inhibitory molecule, IκB, which is degraded prior to translocation of NF-κB to the nucleus. The effect of IgA on IL-8 mRNA production was determined by RNAse protection assay. Results IgA increased (1) NF-κB DNA binding by EMSA, (2) IκB degradation on western blots, and (3) IL-8 mRNA production in CALU-3 cells compared to media alone. Conclusions IgA increases NF-κB activity in CALU-3 cells. Although IgA should contribute to protective immune defense, this protein may inadvertently exacerbate CF lung disease. Increased levels of IgA during infectious exacerbations may further increase NF-κB activity, IL-8 production and neutrophil recruitment resulting in further epithelial damage. However, the effect of IgA on cells with mutant CFTR needs to be determined.

Role of IgA in IgA nephropathy

IgA nephropathy (Berger disease) is defined by the dominant or codominant deposition of IgA in the renal mesangium. There is much evidence in vitro to suggest up-regulation of the IgA immune response in patients. Data from tonsillar and bone marrow-derived lymphocytes and from in vivo immunization studies indicate that the primary defect is an up-regulated systemic one, rather than mucosal IgA production. Several lines of evidence suggest that increased IgA production alone is inadequate to explain the pathogenesis of Berger disease. Murine models of IgA nephropathy indicate that local complement activation mediated by deposited IgG is essential for mesangial cell proliferation and subsequent renal injury. Circulating immune complexes from patients with Berger disease contain IgA and IgG within the same lattice. In vitro studies of model immune aggregates containing various mixtures of IgA and IgG indicate that the IgG is the site of complement activation and fixation. The IgA in the aggregate actually inhibits both complement activation and binding to erythrocyte complement receptor CR1. This effect of IgA may prevent effective immune complex clearance. In future studies, more emphasis should be placed on the roles of IgG and complement in the pathogenesis of IgA nephropathy.

IgA-induced chemokinesis of human polymorphonuclear neutrophils: Requirement of their Fc-alpha receptor

The influence of purified human immunoglobulins on the migration of human neutrophils (PMN) was measured in a 48-well micro chemotaxis chamber, with results expressed as percentages of maximal formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated chemotaxis. Both monomeric and polymeric IgA, of both subclasses, in monoclonal and polyclonal form, as well as secretory IgA and Fc-alpha, but not Fab-alpha fragments, enhanced PMN migration when present either in the lower or in both compartments of the chamber (chemokinesis) at concns as low as 0.l mg ml . IgM and IgE had no such effect. In contrast, IgG was chemotactic at low concn (0.1 mg ml ). Both monomeric and polymeric IgA decreased the maximally induced FMLP-chemotaxis, but IgA increased chemotaxis induced by suboptimal levels of FMLP. Binding of 3[H]-FMLP to PMN was not affected. Cytofluorographic analysis revealed that, under the conditions of the assay, IgA did bind to 93% of PMN. Thus, the various forms of IgA have a dual effect on human PMN mobility: (1) increase PMN random migration (chemokinesis); and (2) decrease the maximal FMLP-induced chemotaxis. Our data support the requirement of binding of IgA to the Fc-alpha receptor of PMN for expression of these activities. This effect of IgA on PMN mobility may be relevant in IgA deficiency states.

Mise en évidence et caractérisation des complexes formés entre les immunoglobulines a (IgA )du colostrum humain et la trypsine ou la chymotrypsine

Proteins of human colostrum, with a molecular weight higher than 200000 and binding trypsin or chymotrypsin were purified by a method involving ammonium sulfate precipitation, gel filtration on Sephadex G-200 and chromatography on DEAE-cellulose. The isolated protein was pure in immunoelectrophoresis, in disc electrophoresis and had a sedimentation coefficient of 12 S. By immunoelectrophoresis against a specific anti-IgA immune serum, it was identified as immunoglobulin A. The effect of IgA on the esterolytic activities of trypsin and chymotrypsin was investigated. Michaelis constants of the complexes were determined by the method of Eadie. The order of affinity for IgA was trypsin > chymotrypsin. The bound enzymes were not protected from soybean trypsin inhibitor or diisopropyl fluorophosphate, but they kept their proteolytic activity. Properties of these complexes were compared with α-macroglobulin-enzyme complexes. The self-protective activity of colostral IgA against tryptic digestion and the role of secretory piece were discussed.