Levels Of Immunoglobulin A Antibodies Research Articles

Evaluation of the clinical use and impact of Miao medicine's anti influenza mask on IgA in human serum and SIgA in nasal mucosa

Purpose: To investigate the clinical use of anti-influenza mask of Miao medicine, and its effect on human serum immunoglobulin A (IgA) as well as nasal mucosa secretory immunoglobulin A (SIgA).
 Methods: 500 patients without COVID-19 in QianDongNanZhou Hospital of Traditional Chinese Medicine from January 2020 to September 2022 were selected and randomly divided into study and control groups, with 250 patients in each group. Both groups wore masks for three months. Control group was given disposable medical surgical three-layer melt-blown non-woven masks, while study group was given Miao medicine anti-infection masks. Serum IgA and SIgA levels were compared before and after wearing masks in both groups.
 Results: Prior to intervention, serum IgA and SIgA levels in nasal mucosa were not significantly different (p > 0.05). There were also no significant differences in blood IgA levels between control and study groups. Before wearing masks, the study group had higher levels of blood IgA and nasal mucosal SIgA than control group. After wearing masks, nasal mucosa SIgA antibody levels and blood IgA antibody levels were significantly higher in the study group compared to control group (p < 0.001). The frequency of adverse responses did not significantly differ between the two groups (p > 0.05).
 Conclusion: Miao medicine anti-infection masks are safe and raise serum levels of COVID-19 IgA antibodies and nasal mucosa SIgA levels in populations susceptible to COVID-19. These properties need to be compared among different races for the purpose of validation

A Case of Celiac Disease with Pericardial Effusion

Celiac disease is a unique enteropathic immune disorder and is now considered a distinct disease entity with protein manifestation and worldwide distribution. The deposition of immune complexes in the small intestine could be a possible reason for the extraintestinal autoimmune manifestations of Celiac disease. Pericardial effusion, though rare in adults, is likely a result of these autoimmune disorders related to Celiac disease. In present study case report, the authors present the case of a 67-year-old female patient with generalised oedema, anasarca, and pitting oedema in the lower extremities. Due to multiple episodes of vomiting, upper gastrointestinal endoscopy was performed, which revealed atrophic duodenal mucosa, and duodenal biopsies were taken from the second part of the duodenum (D2 biopsies). The possibility of Celiac disease was considered, and anti-deamidated gliadin peptide, Immunoglobulin A (IgA), and Immunoglobulin G (IgG) antibodies were sent. Celiac disease was diagnosed based on elevated serum levels of anti-deamidated gliadin peptide, IgA, and IgG antibodies, as well as histologic findings in the small bowel (duodenal biopsies D2). During the thorough evaluation, pericardial effusion was incidentally detected. Celiac disease is an autoimmune disorder in which exposure to gluten triggers inflammation in genetically predisposed individuals. The illness is estimated to have a prevalence of 2%, and most affected people remain undiagnosed. Pericardial effusion is a possible manifestation of Celiac disease, but there is currently no evidence that the disease directly causes the effusion.

A Case of Celiac Disease with Pericardial Effusion

Celiac disease is a unique enteropathic immune disorder and is now considered a distinct disease entity with protein manifestation and worldwide distribution. The deposition of immune complexes in the small intestine could be a possible reason for the extraintestinal autoimmune manifestations of Celiac disease. Pericardial effusion, though rare in adults, is likely a result of these autoimmune disorders related to Celiac disease. In present study case report, the authors present the case of a 67-year-old female patient with generalised oedema, anasarca, and pitting oedema in the lower extremities. Due to multiple episodes of vomiting, upper gastrointestinal endoscopy was performed, which revealed atrophic duodenal mucosa, and duodenal biopsies were taken from the second part of the duodenum (D2 biopsies). The possibility of Celiac disease was considered, and anti-deamidated gliadin peptide, Immunoglobulin A (IgA), and Immunoglobulin G (IgG) antibodies were sent. Celiac disease was diagnosed based on elevated serum levels of anti-deamidated gliadin peptide, IgA, and IgG antibodies, as well as histologic findings in the small bowel (duodenal biopsies D2). During the thorough evaluation, pericardial effusion was incidentally detected. Celiac disease is an autoimmune disorder in which exposure to gluten triggers inflammation in genetically predisposed individuals. The illness is estimated to have a prevalence of 2%, and most affected people remain undiagnosed. Pericardial effusion is a possible manifestation of Celiac disease, but there is currently no evidence that the disease directly causes the effusion.

Childhood Apraxia of Speech: Exploring Gluten Sensitivity and Changes in Glutamate and Gamma-Aminobutyric Acid Plasma Levels

BackgroundIndividuals with childhood apraxia of speech (CAS) were reported to have genetic variations related to gluten sensitivity and some neuroanatomic changes, which could be associated with alterations in neurotransmitters levels such as glutamate and gamma-aminobutyric acid (GABA). The aim was to measure the levels of antigliadin immunoglobulin A (IgA) antibody, glutamate, and GABA in the plasma of children with CAS compared with children with delayed language development (DLD) and neurotypical (NT) children. MethodsThe participants (N = 120) were in three groups: Group I for CAS (N = 30), Group II for DLD (N = 60), and Group III for NT (N = 30). The abilities of children in Groups I and II were evaluated. The plasma levels of antigliadin IgA, glutamate, and GABA were determined by enzyme-linked immunosorbent assay. ResultsThe intelligence quotient and expressive language age in Group I were low compared with Group II (P = 0.001; 0.004). The levels of antigliadin IgA and glutamate in Group I were higher compared with the other two groups, whereas the level of GABA was lower (P < 0.0001). An imbalance between glutamate and GABA was found in Group I. In Group II, no measures differed from NTs except lower GABA levels (P = 0.0007). ConclusionsThe elevated levels of antigliadin IgA antibody and glutamate demonstrated high sensitivity and specificity, differentiating children with CAS from children with DLD and NT children. The low levels of GABA contributed to the imbalance between the excitatory and inhibitory neurotransmitters’ levels detected in children with CAS.

Use of Anti-Glycopeptidolipid-Core Antibodies Serology for Diagnosis and Monitoring of Mycobacterium avium Complex Pulmonary Disease in the United States.

There is an unmet need for rapid, accurate, and noninvasive assays for diagnosis and monitoring of Mycobacterium avium complex pulmonary disease (MAC-PD). We evaluated the diagnostic accuracy of an anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody test in a US cohort of MAC patients, and we described serial serology changes during antimicrobial therapy. We identified serum samples from MAC patients starting treatment at enrollment and control subjects with or without bronchiectasis within OHSU's NTM Biobank. We conducted diagnostic test accuracy. Changes in mean levels of anti-GPL-core IgA antibodies between 0 and 3, 6, or 12 months after treatment start were assessed using the Student's paired t test. Pearson's correlation coefficient was calculated for IgA antibody levels and Student paired t test measures. We included 25 MAC patients and 18 controls. At baseline, IgA antibody concentrations in MAC patients (3.40 ± 6.77 U/mL) were significantly higher than in controls without bronchiectasis (0.14 ± 0.03 U/mL, P = .02). Sensitivity and specificity for MAC-PD in this population was 48% and 89% (cutoff point 0.7 U/mL), respectively. Among MAC patients starting antimicrobial therapy, mean IgA levels decreased 0.3202 U/mL (P = .86) at month 3, 0.8678 U/mL (P = .47) at month 6, and 1.9816 U/mL (P = .41) at 1 year. Quality of Life-Bronchiectasis Respiratory Symptom Scale improvement correlated with decreasing IgA titers after 12 months of treatment in MAC patients (r = -0.50, P = .06). Anti-GPL-core IgA antibody levels are relatively specific for MAC-PD and decrease with treatment. Larger studies are warranted to evaluate the role of IgA serology in monitoring treatment response or for disease relapse/reinfection.

Antibodies Against SARS-CoV-2 in Human Milk: Milk Conversion Rates in the Netherlands.

It has been demonstrated that human milk from mothers who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains antibodies against the virus, which could play an important role in protecting the recipient infant against coronavirus disease 2019 (COVID-19). Seroconversion is measured frequently around the world, but the milk conversion rate is unknown. To determine (1) the prevalence and (2) the dynamics of immunoglobulin A (IgA) antibodies against SARS-CoV-2 in human milk amongst lactating mothers in the Netherlands. In this large prospective cohort study, lactating mothers (N = 2312) were included between October 12, 2020 and February 24, 2021. Enzyme-linked immunosorbent assay was used to determine levels of IgA antibodies in human milk and immunoglobulin G (IgG) antibodies in serum against the ectodomain of the SARS-CoV-2 spike protein. A total of 691 (30.6%) participants had SARS-CoV-2 specific antibodies in human milk and/or serum. Of these participants, 524 (23.1%) had IgA antibodies against SARS-CoV-2 in human milk, and 356 (15.7%) had IgG antibodies against SARS-CoV-2 in serum. A total of 199 (8.8%) participants had antibodies in both human milk and serum. SARS-CoV-2 specific IgA antibodies in human milk remain present at least 10 months after a polymerase chain reaction confirmed infection. The prevalence of IgA antibodies against SARS-CoV-2 in human milk was 23.1% in our cohort. This high prevalence of antibodies in human milk might lead to passive immunity in many breastfed infants and may serve as protection against COVID-19.

Enhanced Humoral Immune Responses against Toxin A and B of Clostridium difficile is Associated with a Milder Disease Manifestation.

The role of the humoral immune response to Clostridium difficile in modulating the severity of C. difficile infection (CDI) is unclear. We compared the levels of serum immunoglobulin G (IgG) and immunoglobulin A (IgA) against toxin A (TcdA) and toxin B (TcdB) of C. difficile between CDI and control patients and according to disease severity. The levels of IgG and IgA antibodies against TcdA and TcdB were measured in sera from patients with CDI (n = 50; 19 had severe CDI) and control patients (n = 52), using ELISA. Patients with CDI had higher levels of IgG antibodies against TcdA and TcdB than controls (p = 0.001 and p = 0.04, respectively). Higher IgG levels against TcdA and TcdB were found in patients with mild vs. severe CDI 7–14 days after the diagnosis (p = 0.004 and 0.036, respectively). A factor analysis included both IgA and IgG levels against both toxins into one composite variable, which was of higher values in patients with mild vs. severe CDI (p = 0.026). In conclusion, the systemic humoral immune responses against TcdA and TcdB might modulate the severity of CDI. These preliminary findings provide a basis for future large-scale studies and support the development and evaluation of active and passive immunotherapies for CDI management.

Serum immunoglobulin a antibodies to glycopeptidolipid core antigen for Mycobacteroides abscessus complex lung disease.

Mycobacteroides abscessus complex (MABC) exhibits smooth morphotypes, expressing glycopeptidolipid (GPL), and rough morphotypes, expressing diminished GPL, on the MABC cell wall. Few reports have focused on the relationship between anti-GPL-core immunoglobulin A (IgA) antibody and colony morphology in MABC lung disease. This study aimed to test GPL core antigen in patients with MABC lung disease to investigate the relationship between coinfection/contamination in other nontuberculous mycobacteria species and colony morphology variant in MABC isolates. Patients with MABC lung disease and contamination diagnosed between 2012 and 2017 at our hospital were enrolled retrospectively. Of the assessed patients, 43 patients with MABC lung disease and 13 with MABC contamination were included. There was a significant difference in anti-GPL-core IgA antibody levels between them (P = 0.02). Forty-three patients with MABC lung disease were divided into two groups as positive and negative antibodies groups. A significant increase in the positive anti-GPL-core IgA antibody was observed in coexistence with both Mycobacterium avium complex (MAC) (P = 0.02) and the isolate of the smooth variant (P = 0.03) in MABC. Anti-GPL-core IgA antibodies in patients with MABC are greatly influenced by MAC coexistence, and colony morphology variant of the MABC isolate.

IgA Antibodies Against Gliadin and Tissue Transglutaminase in Dogs With Chronic Enteritis and Intestinal T-Cell Lymphoma.

Molecular clonality analysis of T-cell receptor (TCR) genes for diagnosing T-cell lymphoma is widely used in veterinary medicine. However, differentiating chronic enteritis (CE) from intestinal lymphoma is challenging because of the incompatibility between histopathologic and clonality analysis results. On the basis of findings that canine intestinal T-cell lymphoma and celiac disease share some common features, we conducted serologic examinations in combination with histopathologic and T-cell receptor clonality analyses in 48 dogs diagnosed with either CE or intestinal lymphoma. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against gliadin and tissue transglutaminase (tTG) were quantitatively measured using ELISA. The conditions were classified according to the histopathologic diagnosis, clonality analysis, and combined histopathologic/clonality analysis. Histopathologic analysis showed that dogs with intestinal lymphoma were likely to have high levels of serum IgA antibodies against gliadin and tTG, and serum IgG antibodies against tTG. No correlation between the diagnosed groups and control group was observed in the results of the clonality analysis and histopathologic/clonality analysis. It is interesting that dogs with intestinal lymphoma had a higher serum IgA titer against gliadin and tTG than did dogs with CE. These results suggest an association between repetitive inflammatory stimulation by gliadin peptides and subsequent intestinal lymphoma in dogs.

Changes in Serum IgA Antibody Levels against the Glycopeptidolipid Core Antigen during Antibiotic Treatment of Mycobacterium avium Complex Lung Disease.

We evaluated serial changes in the levels of serum immunoglobulin A (IgA) antibody to the glycopeptidolipid (GPL) core antigen during antibiotic treatment in 57 patients with Mycobacterium avium complex (MAC) lung disease at baseline (T0) and after 3 months (T3) and 6 months (T6) of treatment. The median patient age was 59 years, and 37 (65%) patients were women. The etiologic organisms included M. avium in 32 (56%) patients and M. intracellulare in 25 (44%) patients. Seven (12%) patients had the fibrocavitary form of the disease on computed tomography. After 12 months of treatment, 42 (74%) patients had a favorable response to treatment, whereas 15 (26%) patients had an unfavorable response to treatment defined as the absence of sputum culture conversion within 12 months of treatment. The initial median serum anti-GPL IgA levels in the 57 patients was 3.50 U/mL, and the antibody levels at T0 (median 3.50 U/mL), T3 (median 2.71 U/mL), and T6 (median 2.61 U/mL) were significantly decreased following treatment (P ＜ 0.001). The results of the multivariate analysis indicated that an initially elevated anti-GPL IgA level (＞ 3.50 U/mL) was associated with an unfavorable response (P = 0.049). Our data suggest that elevated anti-GPL IgA levels may reflect disease activity and may help predict treatment response in patients with MAC lung disease.

Immunoglobulin A as an early humoral responder after mucosal avian coronavirus vaccination.

Infectious bronchitis virus (IBV) is a highly contagious coronavirus prevalent in all countries with an extensive poultry industry and continues to cause economic losses. IBV strains of the Ark serotype are highly prevalent in the Southeastern United States despite extensive vaccination. One explanation for this observation is the high genetic variability of IBV. In addition, IBV Ark-type vaccines may induce suboptimal mucosal immune responses, contributing to the prevalence and persistence of the Ark serotype. To test this hypothesis, chickens were ocularly vaccinated with a commercially available live attenuated IBV Ark-Delmarva Poultry Industry vaccine strain and both mucosal and systemic antibody responses were measured. The highest immunoglobulin A (IgA) spot-forming cell (SFC) response was observed in the Harderian glands (HG) and to a lesser extent in the spleen and conjunctiva-associated lymphoid tissues, while a limited IgG SFC response was observed in either the mucosal or systemic immune compartment. Interestingly, the peak IgA SFC response occurred 2 days earlier in spleen than in the head-associated lymphoid tissues despite ocular vaccination. Furthermore, IgA IBV-specific antibody levels significantly increased over controls 3 days earlier in tears and 4 days earlier in plasma than did IgG antibodies. IgA antibody levels were higher than IgG antibody levels throughout the primary response in tears and were similar in magnitude in plasma. In addition, a very early increase in IgA antibodies on day 3 postvaccination was observed in tears; such a response was not observed in plasma. This early increase is consistent with a mucosal T-independent IgA response to IBV. In the secondary response the IBV antibody levels significantly increased over controls starting on day 1 after boosting, and the IgG antibody levels were higher than the IgA antibody levels in both tears and plasma. In summary, ocular vaccination induced higher IgA antibodies in the primary IBV response, while the memory response is dominated by IgG antibodies. Thus, lower mucosal IgA antibody levels are observed upon secondary exposure to IBV, which may contribute to vulnerability of host epithelial cells to infection by IBV and persistence of the Ark serotype.

Cutaneous expressions of interleukin-6 and neutrophil elastase as well as levels of serum IgA antibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase: implications for both autoimmunity and autoinflammation involvement in dermatitis herpetiformis.

IntroductionDermatitis herpetiformis (DH) seems to be a chronic immune-mediated inflammatory disease of partially known origin. In light of its known biological functions and its involvement in tissue pathology in other disease states, particularly in nickel-induced allergic contact dermatitis coexisting with DH, it would appear that the central and peripheral response by neutrophils and their mediators (e.g. neutrophil elastase – NE) in DH may be partially mediated by interleukin-6 (IL-6).The aim of the study was to assess the role of IL -6 in DH lesions by examining the relationships between IL -6/NE cutaneous expression and levels of serum anti-nonapeptides of gliadin (npG) IgA, anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), anti-epidermal transglutaminase (eTG) IgA in DH.Material and methodsIn total, 24 DH patients having IgA cutaneous deposition were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of IL -6 and NE cutaneous expressions. Levels of serum anti-npG IgA, anti-tTG IgA and anti-eTG IgA were evaluated with ELISA.ResultsWe found no statistically significant correlation between the NE and IL -6 expression intensities. Our results revealed also a lack of correlations between NE/IL -6 expressions and levels of anti-npG IgA, anti-tTG IgA, anti-eTG IgA in DH. However, the IL -6 expression level was significantly lower than that of NE.ConclusionsThe lack of correlations suggested no substantial interactions between IL -6, NE, IgA/npG, IgA/tTG or IgA/eTG in DH. Presented results might indicate the heterogenetic nature of DH pathogenesis suggesting further that both autoimmune and autoinflammatory phenomena may be involved in DH cutaneous pathology.

Seroepidemiology of Norovirus‐Associated Travelers' Diarrhea

Noroviruses (NoVs) are the most common cause of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and were recently identified as a leading cause of travelers' diarrhea (TD) in US and European travelers to Mexico, Guatemala, and India. Serum and diarrheic stool samples were collected from 75 US student travelers to Cuernavaca, Mexico, who developed TD. NoV RNA was detected in acute diarrheic stool samples using reverse transcription-polymerase chain reaction (RT-PCR). Serology assays were performed using GI.1 Norwalk virus (NV) and GII.4 Houston virus (HOV) virus-like particles (VLPs) to measure serum levels of immunoglobulin A (IgA) and IgG by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA); serum IgM was measured by capture enzyme-linked immunosorbent assay (ELISA), and the 50% antibody-blocking titer (BT50 ) was determined by a carbohydrate-blocking assay. NoV infection was identified in 12 (16%; 9 GI-NoV and 3 GII-NoV) of 75 travelers by either RT-PCR or fourfold or more rise in antibody titer. Significantly more individuals had detectable preexisting IgA antibodies against HOV (62/75, 83%) than against NV (49/75, 65%) (p = 0.025) VLPs. A significant difference was observed between NV- and HOV-specific preexisting IgA antibody levels (p = 0.0037), IgG (p = 0.003), and BT50 (p = <0.0001). None of the NoV-infected TD travelers had BT50 > 200, a level that has been described previously as a possible correlate of protection. We found that GI-NoVs are commonly associated with TD cases identified in US adults traveling to Mexico, and seroprevalence rates and geometric mean antibody levels to a GI-NoV were lower than to a GII-NoV strain.

Probiotic Lactobacillus rhamnosus GG Modulates the Mucosal Immune Response in Giardia intestinalis-Infected BALB/c Mice

Gut homeostasis can be altered by the oral administration of health-promoting microorganisms, namely probiotics that are known to reinforce the host immune response. The aim of this study was to elucidate the immunomodulatory effect of orally administered probiotic Lactobacillus rhamnosus GG (LGG) in Giardia-infected mice. BALB/c mice were fed orally with probiotic LGG either 7 days prior to or simultaneously with the challenge dose of Giardia trophozoites. The administration of the probiotic was continued for 25 days, and immunomodulatory potentials in terms of secretory immunoglobulin A (IgA) levels, CD8+ and CD4+ T lymphocytes, and expression of pro-inflammatory [tumor necrosis factor-alpha, interferon-gamma (INF-γ)] and anti-inflammatory cytokines [interleukin (IL)-4, IL-6, IL-10] were studied. Oral feeding of LGG prior to or simultaneously with the test dose of Giardia seems to have modulated both arms (humoral and cellular) of the mucosal immune system since a significant increase in the levels of specific secretory IgA antibody, IgA+ cells, and CD4+ T lymphocytes were observed in contrast with the decreased percentage of cytotoxic CD8+ T lymphocytes. The stimulated mucosal immune response in probiotic fed Giardia-infected mice was further correlated with the enhanced levels of anti-inflammatory cytokines IL-6 and IL-10 and reduced levels of pro-inflammatory cytokine INF-γ. This is the first study to show that oral administration of the effective probiotic LGG to Giardia infected mice could be used as a bacterio-therapy that restores the normal gut microflora and modulates the mucosal immune response.

Intranasal DNA Vaccination Induces Potent Mucosal and Systemic Immune Responses and Cross-protective Immunity Against Influenza Viruses

The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following intranasal administration of luciferase-coding DNA. Using PEI formulation, intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or intranasal immunization with naked-DNA. Furthermore, intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of intranasal DNA as an effective vaccination route.

Application of Ulex europaeus Agglutinin I-Modified Liposomes for Oral Vaccine: Ex Vivo Bioadhesion and in Vivo Immunity

The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines.

Mesenteric lymph nodes are not required for an intestinal immunoglobulin A response to oral cholera toxin

Stimulation of the adaptive immune system in the gut is thought to be mainly initiated in the Peyer's patches as well as in the mesenteric lymph nodes (mLNs) and results in immunoglobulin A (IgA) secretion by plasma cells in the lamina propria. However, the precise role of the mLNs in the development of IgA immune responses is poorly understood. Thus, cholera toxin (CT) was administered to mLN-resected and mLN-bearing animals and the IgA response to CT in the intestine and serum was examined. Levels of CT-specific IgA antibodies and the numbers of cells producing these antibodies in the intestine were increased in mLN-resected rats. Particularly in the distal parts of the intestine, the jejunum and the ileum, IgA responses to orally administered antigens developed were stronger in the intestine after removal of the mLNs. This strongly indicates that the mLNs play a critical role in modulating the expansion of specific IgA responses. After removal of the mLNs, the lymph from the gut flows directly into the blood. It was investigated whether the spleen is involved in the initiation of an immune response to orally administered CT after removal of the mLNs. In the spleens of mLN-resected animals, proliferation was up-regulated, and germinal centres were formed in the follicles. However, CT-specific IgM(+) cells, but no IgA(+) cells, developed. Additionally, an increase of CT-specific IgM in the serum was found in mLN-resected animals. Thus, the data indicate that the spleen is involved in the immune response to CT after mLN resection.

IgA Immune Responses Against Acetaldehyde Adducts and Biomarkers of Alcohol Consumption in Patients with IgA Glomerulonephritis

The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined. A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self-reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT), glutamyl transferase, gamma-CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde-protein adducts. In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and gamma -CDT, p < 0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake. These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted.

T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation and the severity of experimental IgA nephropathy

Immunoglobulin A (IgA) glycosylation, recognized as an important pathogenic factor in IgA nephropathy (IgAN), is apparently controlled by the polarity of T helper (Th) cytokine responses. To examine the role of cytokine polarity in IgAN, inbred mice were immunized by intraperitoneal priming with inactivated Sendai virus (SeV) emulsified in either complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA), which promote Th1- or Th2-immune response, respectively, and then boosted identically twice orally with aqueous suspensions of inactivated virus. Next, some mice were challenged intranasally with infectious SeV. Mice primed with CFA or IFA had equal reductions in nasal viral titre relative to non-immune controls, and equally increased serum levels of SeV-specific IgA antibody. Mice primed with CFA showed higher SeV-specific IgG than those with IFA. Splenocytes from mice primed with IFA produced copious amounts of interleukin (IL)-4 and IL-5, but little interferon-gamma and IL-2; those primed with CFA had reciprocal cytokine recall responses. Total serum IgA and especially SeV-specific IgA from mice primed with IFA showed a selective defect in sialylation and galactosylation. Although the frequency and intensity of glomerular deposits and haematuria did not differ, glomerulonephritis in mice primed with IFA and challenged with infectious virus was more severe than in those given CFA, as judged by serum creatinine level. We conclude that the polarity of T cell cytokines controls the pattern of IgA glycosylation and exerts direct or indirect effects on functional glomerular responses to immune complex deposition.

Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

The interplay between mucosal immune responses to natural exposure to mutans streptococci and the incorporation and accumulation of these cariogenic microorganisms in oral biofilms is unclear. An initial approach to explore this question would be to assess the native secretory immunity emerging as a consequence of Streptococcus mutans infection. To this end, we analyzed salivary immunoglobulin A (IgA) antibody to mutans streptococcal glucosyltransferase (Gtf) and glucan binding protein B (GbpB) and to domains associated with enzyme function and major histocompatibility complex (MHC) class II binding in two experiments. Salivas were collected from approximately 45-day-old Sprague-Dawley rats, which were then infected with S. mutans SJ32. Infection was verified and allowed to continue for 2 to 2.5 months. Salivas were again collected following the infection period. Pre- and postinfection salivas were then analyzed for IgA antibody activity using peptide- or protein-coated microsphere Luminex technology. S. mutans infection induced significant levels of salivary IgA antibody to Gtf (P < 0.002) and GbpB (P < 0.001) in both experiments, although the levels were usually far lower than the levels achieved when mucosal immunization is used. Significantly (P < 0.035 to P < 0.001) elevated levels of postinfection salivary IgA antibody to 6/10 Gtf peptides associated with either enzyme function or MHC binding were detected. The postinfection levels of antibody to two GbpB peptides in the N-terminal region of the six GbpB peptides assayed were also elevated (P < 0.031 and P < 0.001). Interestingly, the patterns of the rodent response to GbpB peptides were similar to the patterns seen in salivas from young children during their initial exposure to S. mutans. Thus, the presence of a detectable postinfection salivary IgA response to mutans streptococcal virulence-associated components, coupled with the correspondence between rat and human mucosal immune responsiveness to naturally presented Gtf and GbpB epitopes, suggests that the rat may be a useful model for defining mucosal responses that could be expected in humans. Under controlled infection conditions, such a model could prove to be helpful for unraveling relationships between the host response and oral biofilm development.