Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis.

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.

Salivary immunoglobulin levels and periodontal indices in Brazilian children with and without type 1 diabetes.

This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; ß=0.363), gingival index (p=0.041; ß=0.398), and plaque index (p=0.008; ß=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.

Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response.

Introduction: Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.4 and BA.5 variants. Methods: We recruited volunteers from University of Massachusetts student, faculty and staff members to provide samples of blood and saliva at four different time points, including pre-boost and three times post boost and analyzed samples for antibody production as well as neutralization of virus. Results: Our data provide a comprehensive analysis of the antibody response following a single dose of the bivalent boost over a 6-month period and support previous findings that the response induced after the bivalent boost does not create a strong BA.4/BA.5-specific antibody response. Conclusion: We found no evidence of a specific anti-BA.4/BA.5 response developing over time, including in a sub-population of individuals who become infected after a single dose of the bivalent booster. Additionally, we present data that support the use of saliva samples as a reliable alternative to blood for antibody detection against specific SARS-CoV-2 antigens.

Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study.

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

HA2-FimA DNA Vaccine Treats Experimental Periodontitis.

PURPOSE: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. MATERIALS AND METHODS: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2-FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). RESULTS: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). Micro-CT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). CONCLUSION: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.

Antigen-functionalized turnip mosaic virus nanoparticles increase antibody sensing in saliva. A case study with SARS-CoV-2 RBD.

Nanoparticles derived from plant viruses play an important role in nanomedicine due to their biocompatibility, self-assembly and easily-modifiable surface. In this study, we developed a novel platform for increasing antibody sensing using viral nanoparticles derived from turnip mosaic virus (TuMV) functionalized with SARS-CoV-2 receptor binding domain (RBD) through three different methods: chemical conjugation, gene fusion and the SpyTag/SpyCatcher technology. Even though gene fusion turned out to be unsuccessful, the other two constructs were proven to significantly increase antibody sensing when tested with saliva of patients with different infection and vaccination status to SARS-CoV-2. Our findings show the high potential of TuMV nanoparticles in the fields of diagnostics and immunodetection, being especially attractive for the development of novel antibody sensing devices.

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination.

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Effect of the probiotic Weissella cibaria CMS1 on the immune response and the oral microbiome: a randomized, double-blind, placebo-controlled, parallel study.

The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in overall health and immune defense against external threats. Recently, the potential use of probiotics for disease prevention and treatment has gained attention. This study aimed to assess the effect of Weissella cibaria CMS1 (W. cibaria CMS1) consumption on the oral microbiome and immune function in healthy individuals through a 12-week clinical trial. This randomized, double-blind, placebo-controlled, parallel trial enrolled 90 healthy subjects. The consumption of W. cibaria CMS1 significantly increased salivary immunoglobulin A (p = 0.046) and decreased tumor necrosis factor-α (TNF-α) levels (p = 0.008). Analysis of the oral microbiota revealed changes in beta diversity, increased abundance of Firmicutes and Actinobacteria, and decreased abundance of Bacteroidetes and Fusobacteria after 12 weeks of consuming W. cibaria CMS1. Significant increases in various strains, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus, and Firmicutes, were observed in the W. cibaria CMS1 group after 12 weeks of intake. Additionally, Fusobacteriia Fusobacteriales Fusobacteriaceae and Fusobacteriia Fusobacteriales Fusobacteriaceae Fusobacterium exhibited a positive correlation with TNF-α. These findings demonstrate the positive effect of W. cibaria CMS1 on the oral environment and immune function.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2.

SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding of the protection against infection with SARS-CoV-2 is critical to ending the pandemic. Serological assays have been widely used to assess immune responses, but secretory antibodies, the essential first line of defense, have been studied to only a limited extent. Of particular interest and importance are neutralizing antibodies, which block the binding of the spike protein of SARS-CoV-2 to the human receptor angiotensin-converting enzyme-2 (ACE2) and thus are essential for immune defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, to characterize neutralizing antibody affinity to SARS-CoV-2 spike receptor-binding domain (RBD) and spike trimer in saliva. Affinity measurement was obtained through a contrived sample and buffer using recombinant SARS-CoV-2 RBD and monoclonal antibody. Limited saliva samples demonstrated that MDS applies to saliva neutralizing antibody measurement. The ability to disrupt a complex of ACE2-Fc and spike trimer is shown. Using a quantitative assay on the patient sample, we determined the affinity and binding site concentration of the neutralizing antibodies.

Salivary autoantibodies to type I IFNs: Mirror plasma levels, predispose to severe COVID-19, and enhance feasibility for clinical screening.

BACKGROUND: Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections. OBJECTIVES: This study aimed to evaluate the prevalence of type I IFN aAbs in both plasma and saliva from COVID-19 patients, analyze their neutralizing activity, and examine their associations with clinical outcomes, including the need for mechanical ventilation and in-hospital mortality. METHODS: Prospective analyses of patients admitted to intensive care units in three UAE hospitals from June 2020 to March 2021 were performed to measure aAbs using enzyme-linked immunosorbent assay (ELISA), assess aAbs activity via neutralization assays, and correlate aAbs with clinical outcomes. RESULTS: Type I IFN aAbs (α2 and/or ω) were measured in plasma samples from 213 ICU patients, and positive results were obtained for 20 % (n = 42) of the patients, with half exhibiting neutralizing activity. Saliva samples from a subgroup of 24 patients reflected plasma levels. In multivariate regression analyses, presence of type I IFN aAbs was associated with a higher need for mechanical ventilation (OR 2.58; 95 % CI 1.07-6.22) and greater in-hospital mortality (OR 2.40; 95 % CI 1.13 - 5.07; P = 0.022). Similarly, positive neutralizing aAbs (naAbs) were associated with a greater need for mechanical ventilation (OR 4.96; 95 % CI 1.12-22.07; P = 0.035) and greater odds of in-hospital mortality (OR 2.87; 95 % CI 1.05-7.89; P = 0.041). CONCLUSIONS: Type I IFN autoantibodies can be detected in noninvasive saliva samples, alongside conventional plasma samples, from COVID-19 patients and are associated with worse outcomes, such as greater mechanical ventilation needs and in-hospital mortality.

Comparative study on Saliva and Nasopharyngeal swabs and the outcome of RT-PCR test in patients with mild symptoms of SARS-CoV-2 / Estudio comparativo de muestras de saliva y nasofaríngeas y el resultado de la prueba RT-PCR en pacientes con síntomas leves de SARS-CoV-2

Aim A simple and reliable method for diagnosing COVID 19 infections is the needed. The role of saliva in the transmission of the infection has already been established. Method Saliva and nasopharyngeal swabs from patients suspected to have COVID 19 infections were taken simultaneously, and the results of the RT-PCR were compared. Result Total 405 samples were collected, of which 250 males and 155 females. In the 391 samples included for analysis, 370 (94.63%) samples were found to have concordance results, and 21 (5.37%) samples had discordant results. Conclusion The use of saliva to diagnose COVID 19 infection is reliable, and its use can be recommended. (AU)

Objetivo Un método simple y confiable para diagnosticar infecciones por COVID 19 es necesario. Ya se ha establecido el papel de la saliva en la transmisión de la infección. Método Se tomaron simultáneamente hisopos de saliva y nasofaríngeos de pacientes con sospecha de infección por COVID 19 y se compararon los resultados de la RT-PCR. Resultado Se recogieron 405 muestras, de las cuales 250 hombres y 155 mujeres. En las 391 muestras incluidas para el análisis, se encontró que 370 (94,63%) muestras tenían resultados de concordancia y 21 (5,37%) muestras tenían resultados discordantes. Conclusión El uso de la saliva para diagnosticar la infección por COVID 19 es confiable y se puede recomendar su uso. (AU)

Salivary and serum IgA and IgG responses to SARS-CoV-2-spike protein following SARS-CoV-2 infection and after immunization with COVID-19 vaccines.

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines. Methods: A total of 52 paired saliva and serum samples were collected from 26 study participants: 7 subjects after COVID-19 infection and 19 subjects who were uninfected. The ELISA results from these samples were compared with five prepandemic control serum samples. Total IgG and SARS-CoV-2 spike-specific IgG in the serum samples from the subjects who were infected and vaccinated were also measured in a commercial laboratory with an enzyme immunoassay. Results: A wide variation in antibody responses was seen in salivary and serum samples measured by both methods. Three groups of serum total and IgG spike-specific SARS-CoV-2 antibody responses were observed: (1) low, (2) intermediate, and (3) high antibody responders. A correlational analysis of salivary IgA (sIgA) responses with serum IgG concentrations showed a statistical correlation in the low and intermediate antibody responder groups but not in the high group (which we believe was a result of saturation). Conclusion: These preliminary findings suggest measuring salivary and serum IgG and IgA merit further investigation as markers of current or recent SARS-CoV-2 infections.

Correlation between salivary biomarkers and plaque-induced gingivitis exacerbated by pregnancy

Objetive: To evaluate the correlation between salivary biomarkers (the salivary antioxidant ability, salivary level of polyphenols, and other antioxidants) with plaque-induced gingivitis exacerbated by pregnancy in pregnant and nonpregnant women. Material and Methods: For this observational study, medical records, dental examinations, and analyses of saliva samples were carried out in pregnant and nonpregnant women. A p-value of <0.05 was considered significant. Results: The pregnant women (n =17) exhibited a lower antioxidant capacity (p-value=0.0041), higher levels of polyphenols, gingival index, bleeding on probing, and subjects consuming mineral-enriched products (p-value from <0.0001 to 0.0466), and unchanged levels of phosphotungstic acid reactive substances, proteins, oral hygienic habits, plaque index and probing depth (p-value from 0.0683 to 0.8358), in comparison with the nonpregnant women (n=9). Also, a positive correlation between the gingival index and salivary polyphenol content was observed (r-value = 0.4087, p-value = 0.0202). Conclusion: The salivary polyphenols correlate with plaque-induced gingivitis exacerbated by pregnancy, suggesting a deficiency of salivary antioxidant protection.

Objetivo: Evaluar la correlación entre los biomarcadores salivales (la capacidad antioxidante salival, el nivel salival de polifenoles y otros antioxidantes) con la gingivitis inducida por placa exacerbada por el embarazo en mujeres embarazadas y no embarazadas. Material y Métodos: Para este estudio observacional, se realizaron registros médicos, exámenes dentales y análisis de muestras de saliva en mujeres embarazadas y no embarazadas. Se consideró significativo un valor de p<0,05. Resultados: Las gestantes (n=17) presentaron menor capacidad antioxidante (p=0,0041), mayores niveles de polifenoles, índice gingival, sangrado al sondaje y los sujetos que consumían productos enriquecidos con minerales (p<0,0001 a p<0,0466), y no hubo diferencias en los niveles de sustancias reactivas al ácido fosfotúngstico, proteínas, hábitos de higiene bucal, índice de placa y profundidad de sondaje (p=0,0683 a 0,8358), en comparación con las mujeres no embarazadas (n=19). Además, se observó una correlación positiva entre el índice gingival y elcontenido de polifenoles salivales (r = 0,4087, p= 0,0202). Conclusión: Los polifenoles salivales se correlacionan con la gingivitis inducida por placa y exacerbada por el embarazo, lo que sugiere una deficiencia de protección antioxidante salival.

Oropharyngeal administration of mother's own milk influences levels of salivary sIgA in preterm infants fed by gastric tube.

The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on salivary secretory immunoglobulin A (sIgA) levels in preterm infants fed by gastric tube. Infants (n = 130) with birth weight < 1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The experimental group (n = 65) accepted oropharyngeal mother's milk administration before gastric tube feeding for 14 days after birth. The control group (n = 65) accepted oropharyngeal 0.9% normal saline administration. Saliva concentration of sIgA were assessed at the 2 h, 7th and 14th day after birth. The level of salivary sIgA in experimental group were significantly higher than those in control group on the 7th day after birth (p < 0.05), but there were no differences in salivary sIgA levels on the 14th day between the two groups. The results of quantile regression analysis showed that oropharyngeal mother's milk administration, delivery mode and gestational age had significant effects on the increase of sIgA. SIgA in experimental group and the total number of intervention had a significant positive correlation (p < 0.05). Oropharyngeal mother's milk administration can improve salivary sIgA levels of preterm infants.

Saliva as a useful tool for evaluating upper mucosal antibody response to influenza.

Mucosal immunity plays a crucial role in controlling upper respiratory infections, including influenza. We established a quantitative ELISA to measure the amount of influenza virus-specific salivery IgA (sIgA) and salivary IgG (sIgG) antibodies using a standard antibody broadly reactive to the influenza A virus. We then analyzed saliva and serum samples from seven individuals infected with the A(H1N1)pdm09 influenza virus during the 2019-2020 flu seasons. We detected an early (6-10 days post-infection) increase of sIgA in five of the seven samples and a later (3-5 weeks) increase of sIgG in six of the seven saliva samples. Although the conventional parenteral influenza vaccine did not induce IgA production in saliva, vaccinated individuals with a history of influenza infection had higher basal levels of sIgA than those without a history. Interestingly, we observed sIgA and sIgG in an asymptomatic individual who had close contact with two influenza cases. Both early mucosal sIgA secretion and late systemically induced sIgG in the mucosal surface may protect against virus infection. Despite the small sample size, our results indicate that the saliva test system can be useful for analyzing upper mucosal immunity in influenza.

Cutting Edge: Serum but Not Mucosal Antibody Responses Are Associated with Pre-Existing SARS-CoV-2 Spike Cross-Reactive CD4+ T Cells following BNT162b2 Vaccination in the Elderly.

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine in old (69-92 y) and middle-aged (24-57 y) vaccinees compared with natural infection (COVID-19 convalescents, 21-55 y of age). Serological humoral responses to vaccination excee-ded those of convalescents, but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+ T cells as a predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.

Disease mechanisms in Sjögren's syndrome: What do we know?

Why should we explore and study disease mechanisms? This is particularly important when we are dealing with complex pathogenesis without a direct causal agent, for example, syndromes with multiple organ involvements. Sjögren's syndrome is definitely such an entity. Also, there are a number of reasons for such studies such as disclosing the aetiology, to identify biomarkers for diagnosis and assessment of the disease process and monitor response to treatment, to determine targets for treatment, to define critical items in classification criteria, amongst others. Samples available for the study of disease mechanisms in Sjögren's syndrome have included serum (autoantibodies, cytokines), DNA (gene profiling, GWAS), cells (phenotypes/flow cytometry, proportion of cells/CyTOF), tissue (focal inflammation, germinal centres, mass cytometry), and saliva (proteomics, biochemistry, mucosal immunity). An original explanatory concept for the pathogenesis of Sjögren's syndrome proposed a specific and self-perpetuating immune-mediated loss of exocrine tissue as the principal cause of glandular hypofunction. This hypothesis however falls short of accommodating several Sjögren's syndrome-related phenomena and experimental findings. Today, the emergence of advanced bio-analytical platforms has further enabled the identification of central pathogenic processes and potential biomarkers. The purpose of this minor review is to highlight a selection of previous but also recent and novel aspects on the disease mechanisms in Sjögren's syndrome.

Evaluating immunity to SARS-CoV-2 in nursing home residents using saliva IgG.

BACKGROUND: SARS-CoV-2 circulating variants coupled with waning immunity pose a significant threat to the long-term care (LTC) population. Our objective was to measure salivary IgG antibodies in residents and staff of an LTC facility to (1) evaluate IgG response in saliva post-natural infection and vaccination and (2) assess its feasibility to describe the seroprevalence over time. METHODS: We performed salivary IgG sampling of all residents and staff who agreed to test in a 150-bed skilled nursing facility during three seroprevalence surveys between October 2020 and February 2021. The facility had SARS-CoV-2 outbreaks in May 2020 and November 2020, when 45 of 138 and 37 of 125 residents were infected, respectively; they offered two Federal vaccine clinics in January 2021. We evaluated quantitative IgG in saliva to the Nucleocapsid (N), Spike (S), and Receptor-binding domain (RBD) Antigens of SARS-CoV-2 over time post-infection and post-vaccination. RESULTS: One hundred twenty-four residents and 28 staff underwent saliva serologic testing on one or more survey visits. Over three surveys, the SARS-CoV-2 seroprevalence at the facility was 49%, 64%, and 81%, respectively. IgG to S, RBD, and N Antigens all increased post infection. Post vaccination, the infection naïve group did not have a detectable N IgG level, and N IgG levels for the previously infected did not increase post vaccination (p < 0.001). Fully vaccinated subjects with prior COVID-19 infection had significantly higher RBD and S IgG responses compared with those who were infection-naïve prior to vaccination (p < 0.001 for both). CONCLUSIONS: Positive SARS-COV-2 IgG in saliva was concordant with prior infection (Anti N, S, RBD) and vaccination (Anti S, RBD) and remained above positivity threshold for up to 9 months from infection. Salivary sampling is a non-invasive method of tracking immunity and differentiating between prior infection and vaccination to inform the need for boosters in LTC residents and staff.