Associations Between Secretory Immunoglobulin A and Social Network Structure.

PURPOSE: This study investigates the social determinants of health by examining how mucosal immunity is associated with the patterning of social connections in a network. Studies have suggested that social networks have biological underpinnings, but investigations at the scale of networks, rather than individuals, have remained elusive. We integrate salivary bioscience methods with advanced social network modeling to explore the association between salivary secretory immunoglobulin A (SIgA), a key component of mucosal immunity, and social network structure. METHOD: Friendship network data and saliva samples (later assayed for SIgA) were obtained from a large mixed-gender social organization (n = 155, 55% female, M age = 19.5 years). RESULTS: Exponential random graph modeling revealed that SIgA levels were positively associated with reporting more friendship ties with community members (i.e., social network activity), after controlling for other processes associated with network structure including preference to befriend others of the same age, gender, and extraversion, increased network popularity of agreeable individuals and those with lower levels of perceived stress, as well as network structural and organizational processes. CONCLUSION: By examining a wider range of associations between SIgA and network structure, we pinpoint that SIgA is positively associated with respondent's sociability. Our findings are consistent with social integration theories linking social relationships to health and highlight the role of humoral immunity as a possible mediator of these associations.

The utility of saliva for the assessment of anti-pneumococcal antibodies: investigation of saliva as a marker of antibody status in serum.

CONTEXT: Salivary antibodies may act as non-invasive marker of systemic immunity enabling assessment of vaccination and protection against bacterial infections. OBJECTIVE: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva reflect concentrations in serum and determine whether saliva can accurately identify protective concentrations in serum. METHODS: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 Pn polysaccharide antigens in 72 healthy adults. RESULTS: Antibody levels in saliva correlated positively with serum across immunoglobulin classes, most strongly for IgA. Individuals who had protective antibody levels in serum demonstrated significantly higher IgG and IgA salivary antibody concentrations/secretion rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those with/without protective levels in serum for the majority of serotypes. Salivary IgM antibodies were not able to differentiate protective status. Median IgG and IgA Pn salivary parameters were able to identify individuals who had protective levels in serum on ≥8/12 serotypes with moderate accuracy: median IgA secretion rates provided the best sensitivity (73%) and specificity (71%). CONCLUSIONS: These findings suggest that IgG and IgA Pn specific antibodies in saliva may be useful surrogate markers of antibody status in serum.

Characterization, quantification, and assessment of immune protection potential of secretory immunoglobulin A in colostrum samples from Saudi women.

OBJECTIVE: To characterize, quantify, and assess the function of colostral secretory immunoglobulin A (sIgA) in Saudi women. METHODS: This prospective study was performed between March 2009 and February 2010 at King Khalid University Hospital, Riyadh, Saudi Arabia. Twenty milliliters of colostrum sample was collected from each of 23 healthy Saudi women (mean age 26+/-4 years) included in the study within 48 hours postpartum. Levels of sIgA and sIgM were determined by enzyme-linked immunosorbent assay (ELISA) and purification of secretory antibodies from pooled clarified sample was performed by thiophilic-gel chromatography, Jacalin-agarose chromatography, and Sephacryl S-300 gel filtration. Antibody induced respiratory burst in peripheral blood neutrophils and monocytes was assessed by chemiluminescence. RESULTS: The median concentration of sIgA1 was 0.053 mg/ml, sIgA2 0.047 mg/ml and sIgM 0.067 mg/ml with interquartile ranges of 0.308, 0.158 and 0.150. The levels of antibodies were no different. Whereas, 60% of IgA1 was present in dimeric and 30% in trimeric form; the major bulk of sIgA2 (85%) were comprised of the dimeric form. Both sIgA and serum IgA were able to induce effective and almost identical respiratory bursts in neutrophils and monocytes. CONCLUSION: Dimeric forms of sIgA were the predominant antibodies in colostrum samples and sIgA antibodies exhibited functional similarity with serum IgA.

Single-step turn-on homogeneous fluorescent immunosensor for rapid, sensitive, and selective detection of proteins.

Quick & easy: A simple and positive-readout fluorescent immunosensor was developed based on a quencher composed of a 3 nm gold nanoparticle (GNP) covalently linked to a Fab fragment, which proved to be stable and specific. The method allows for direct and sensitive detection of target antigens in homogeneous solutions in one step without any separation steps. It has been successfully applied to rapidly quantify the amount of secretory immunoglobulin A (sIgA) in human saliva samples.

Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries.

AIM: To prepare a clinical-grade anti-caries DNA vaccine pGJA-P/VAX and explore its immune effect and protective efficacy against a cariogenic bacterial challenge. METHODS: A large-scale industrial production process was developed under Good Manufacturing Practices (GMP) by combining and optimizing common unit operations such as alkaline lysis, precipitation, endotoxin removal and column chromatography. Quality controls of the purified bulk and final lyophilized vaccine were conducted according to authoritative guidelines. Mice and gnotobiotic rats were intranasally immunized with clinical-grade pGJA-P/VAX with chitosan. Antibody levels of serum IgG and salivary SIgA were assessed by an enzyme-linked immunosorbent assay (ELISA), and caries activity was evaluated by the Keyes method. pGJA-P/VAX and pVAX1 prepared by a laboratory-scale commercial kit were used as controls. RESULTS: The production process proved to be scalable and reproducible. Impurities including host protein, residual RNA, genomic DNA and endotoxin in the purified plasmid were all under the limits of set specifications. Intranasal vaccination with clinical-grade pGJA-P/VAX induced higher serum IgG and salivary SIgA in both mice and gnotobiotic rats. While in the experimental caries model, the enamel (E), dentinal slight (Ds), and dentinal moderate (Dm) caries lesions were reduced by 21.1%, 33.0%, and 40.9%, respectively. CONCLUSION: The production process under GMP was efficient in preparing clinical-grade pGJA-P/VAX with high purity and intended effectiveness, thus facilitating future clinical trials for the anti-caries DNA vaccine.

Assessment of the opsonic activity of purified bovine sIgA following intramammary immunization of cows with Staphylococcus aureus.

The phagocytosis of Staphylococcus aureus by bovine polymorphonuclear neutrophils (PMN) requires the presence of antibodies. Among the major isotypes of bovine antibodies, IgG2 and IgM are considered opsonic for bovine PMN. However, the role of purified bovine secretory IgA (sIgA) as an opsonin has not been assessed. In the present study, IgG2 were obtained from serum and sIgA, IgG1, and IgM were purified from the colostrums of three cows intramammarily immunized with heat-killed Staphylococcus aureus. The Ig preparations were assayed for specific antibodies, and the opsonic capacity of every isotype was investigated. Despite the presence of antibodies, we observed no distinct chemiluminescence response of PMN stimulated with sIgA- or IgG1-opsonized S. aureus, whereas IgM or IgG2 bound to bacteria induced a marked chemiluminescence response. Moreover, the counting of internalized bacteria per PMN after phagocytosis revealed a low uptake of S. aureus opsonized with sIgA or IgG1, in contrast to IgM or IgG2, which triggered efficient ingestion of bacteria. Priming of neutrophils by TNF-alpha, IFN-gamma, or C5adesArg did not promote an oxidative burst or uptake of sIgA-opsonized S. aureus to a greater extent than with IgG1-opsonized bacteria. Furthermore, analysis of uningested bacteria by flow cytometry after incubation with PMN showed a preferential uptake of IgM-opsonized S. aureus by PMN and only few sIgA-positive stained bacteria were PMN-associated. These experiments indicate that sIgA, like IgG1 and unlike IgM or IgG2, could not be considered as a major opsonin for phagocytosis of S. aureus by bovine blood PMN.

The pattern of change in salivary immunoglobulins and antibodies to S. mitis and S. oralis in children undergoing bone marrow transplantation: use of an indirect method of assessment.

The objective of this study was to assess the pattern of change in salivary immunoglobulins and antibodies to S. mitis and S. oralis in 23 children following allogeneic bone marrow transplantation and their matched controls. To overcome the difficulty of obtaining a sufficient quantity of whole saliva from very young, sick children saliva was collected in a 5-ml oral rinse of sterile normal saline. It was not possible to measure the volume of whole saliva in each rinse and the concentration of the salivary immunoglobulins and bacterial antibodies were estimated from 1 ml of oral rinse. Despite these shortcomings a pattern of change in the mean concentrations of total salivary IgA, secretory IgA, antibodies to S. mitis and S. oralis and total IgG at specific event- related times during the transplantation period has been demonstrated. There was a significant increase in the concentration of salivary IgG 7 days post-transplantation, followed by significant decreases in total salivary IgA, secretory IgA and antibodies to S. mitis after recovery of the peripheral neutrophil count above 0.5 x 10(9). The concentrations of total IgA and antibodies to S. oralis was significantly greater in the transplant group 119 days post-transplantation.