scholarly journals Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage

2000 ◽  
Vol 68 (7) ◽  
pp. 3830-3839 ◽  
Author(s):  
Dörthe Externest ◽  
Barbara Meckelein ◽  
M. Alexander Schmidt ◽  
Andreas Frey
Keyword(s):  
Cholera Toxin ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Routine Diagnostics ◽  
Significant Relationships ◽  
Serum Igg ◽  
Mucosal Surfaces ◽  
Secretory Immunoglobulin

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.

Induced Polyspecificity of Human Secretory Immunoglobulin A Antibodies: Is It Possible to Improve Their Ability to Bind Pathogens?

Pharmacology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Ekaterina N. Gorshkova ◽  
Shina Pashova ◽  
Ekaterina A. Vasilenko ◽  
Tatiana S. Tchurina ◽  
Elizaveta A. Razzorenova ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antigen Binding ◽  
Secretory Immunoglobulin A ◽  
Acidic Ph ◽  
Ferrous Ions ◽  
Binding Properties ◽  
Binding Behavior ◽  
Secretory Immunoglobulin

<b><i>Introduction:</i></b> As has been shown previously, various protein-modifying agents can change the antigen-binding properties of immunoglobulins. However, induced polyspecificity of human secretory immunoglobulin A (sIgA) has not been previously characterized in detail. <b><i>Methods:</i></b> In the present study, human secretory immunoglobulin A (IgA) was exposed to buffers with acidic pH, to free heme, or to pro-oxidative ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens was compared using Western blotting and enzyme-linked immunosorbent assay. The ability of these agents to modulate the antigen-binding properties of human sIgA toward a wide range of pathogen peptides was investigated using an epitope microarray. <b><i>Results:</i></b> We have shown that acidic pH, heme, and pro-oxidative ferrous ions influenced the binding of secretory IgA in opposite directions (either increasing or decreasing); however, the strongest effect was observed when using buffers with low pH. This fraction had the highest number of affected reactivities; most of them were increased and most of the new ones were toward common pathogens. <b><i>Conclusions:</i></b> Thus, it was shown that all investigated treatments can alter to some degree the antigen-binding of secretory IgA, but acidic pH has the most potentially beneficial effect by increasing binding to a largest number of common pathogens’ antigens.

scholarly journals Immunoglobulins to Group A Streptococcal Surface Molecules Decrease Adherence to and Invasion of Human Pharyngeal Cells

1998 ◽  
Vol 66 (3) ◽  
pp. 974-979 ◽  
Author(s):  
U. Fluckiger ◽  
K. F. Jones ◽  
V. A. Fischetti
Keyword(s):  
Streptococcal Infection ◽  
Immunoglobulin A ◽  
M Protein ◽  
Secretory Iga ◽  
Surface Molecules ◽  
Mucosal Surfaces ◽  
Group A ◽  
Specific Igg ◽  
Secretory Immunoglobulin

ABSTRACT The M protein is one of the most important virulence factors of group A streptococci (Streptococcus pyogenes) and may play an important role in the first steps of streptococcal infection. Since acute pharyngitis is a frequently occurring infectious disease caused by these bacteria, we wished to know whether antibodies to the M protein or other surface components inhibit adherence and internalization of streptococci to pharyngeal cells. We investigated the role of whole human secretory immunoglobulin A (sIgA), M6 protein-specific sIgA, and M6 protein-specific serum IgG in the inhibition of streptococcal adherence and internalization to cultured human pharyngeal cells. S. pyogenes D471, which produces a type 6 M protein (M+), and its isogenic M-negative (M−) derivative JRS75 were tested. Purified whole sIgA, M protein-specific sIgA, and sIgA preabsorbed with M protein were able to decrease significantly the adherence of streptococci to pharyngeal cells. Purified IgG against the M6 protein did not diminish the attachment of streptococci to the pharyngeal cells but did reduce internalization. Thus, our data suggest that secretory IgA may play a key role in preventing streptococcal infection at mucosal surfaces by blocking adherence while affinity-purified anti-M protein-specific IgG blocks epitopes responsible for invasion.

scholarly journals Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

Science ◽  
2019 ◽  
Vol 363 (6430) ◽  
pp. 993-998 ◽  
Author(s):  
Joep Grootjans ◽  
Niklas Krupka ◽  
Shuhei Hosomi ◽  
Juan D. Matute ◽  
Thomas Hanley ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Intestinal Epithelial ◽  
Healthy Humans ◽  
Mucosal Surfaces ◽  
Iga Response ◽  
Independent Expansion ◽  
Secretory Immunoglobulin

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.

Depletion of gut secretory immunoglobulin A coated Lactobacillus reuteri is associated with gestational diabetes mellitus-related intestinal mucosal barrier damage

2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lactobacillus Reuteri ◽  
Immunoglobulin A ◽  
Mucosal Damage ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Secretory Immunoglobulin

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.

scholarly journals Detection of cross-reactive IgA against SARS-CoV-2 spike 1 subunit in saliva

2021 ◽  
Author(s):  
Keiichi Tsukinoki ◽  
Tatsuo Yamamoto ◽  
Keisuke Handa ◽  
Mariko Iwamiya ◽  
Juri Saruta ◽  
...  
Keyword(s):  
Breast Milk ◽  
Recombinant Protein ◽  
University Hospital ◽  
Spike Protein ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Binding Domain ◽  
Blood Samples ◽  
Milk Samples ◽  
Mucosal Surfaces

AbstractAbundant secretory IgA (sIgA) in mucus, breast milk, and saliva provides immunity that prevents infection of mucosal surfaces. sIgA in pre-pandemic breast milk samples have been reported to cross-react with SARS-CoV-2, but whether it also occurs in saliva and, if so, whether it cross-reacts with SARS-CoV-2, has remained unknown. We aimed to clarify whether sIgA in saliva cross-reacts with SARS-CoV-2 spike 1 subunit in individuals who have not been infected with this virus. The study included 137 (male, n = 101; female, n = 36; mean age, 38.7 [24–65] years) of dentists and doctors in the Kanagawa Dental University Hospital. Saliva and blood samples were analyzed by PCR and immunochromatography for IgG and IgM, respectively. We then identified patients with saliva samples that were confirmed as PCR- and IgM-negative for COVID-19. Proportions of SARS-CoV-2 cross-reactive IgA-positive individuals were determined by enzyme-linked immunosorbent assay using a biotin-labeled spike S1-mFc recombinant protein covering the receptor-binding domain of SARS-CoV-2. The proportion of SARS-CoV-2 cross-reactive IgA-positive individuals was 46.7%, and this correlated negatively with age (r = −0.218, p = 0.01). The proportion of IgA-positive individuals ≥ 50 y was significantly lower than that of patients aged ≤ 49 y (p = 0.008). sIgA was purified from the saliva of all patients, and the salivary sIgA was found to suppress the binding of SARS-CoV-2 spike protein to the ACE-2 receptor. We found SARS-CoV-2 cross-reactive sIgA in the saliva of some participants who had never been infected with the virus, suggesting that sIgA helps prevent SARS-CoV-2 infection.

Secretory Immunoglobulin a in Oral and Respiratory Passages in Man

1975 ◽  
Vol 84 (20_suppl) ◽  
pp. 1-23 ◽  
Author(s):  
Goro Mogi
Keyword(s):  
Immunoglobulin A ◽  
Secretory Component ◽  
Secretory Iga ◽  
Secretory Cells ◽  
Antigenic Relationship ◽  
Serum Iga ◽  
Human Colostrum ◽  
Specific Antisera ◽  
Antigenic Relationships ◽  
Secretory Immunoglobulin

Secretory IgA (SIgA) is the predominant immunoglobulin in certain external secretions and may have an important role in immunological mucosal resistance. SIgA differs in chemical and immunological properties from serum IgA. The present study was undertaken to investigate the antigenic relationship between SIgA, free secretory component (FSC) and serum IgA and the localization of SIgA as well as other immunological classes in tissues of oral and respiratory passages by use of immunofluorescence technique. SIgA and FSC were highly purified from human colostrum and rabbit anti-SIgA and anti-SC antisera were prepared. On the basis of antigenic relationships between SIgA, FSC and serum IgA, it was emphasized that individual specific antisera for SC and IgA and/or SIgA should be used in immunochemical or immunohistological investigations for SIgA. The present study failed to detect SC determinants in palatine and lingual tonsils. However, it was evident that cells present in the pharyngeal tonsillar epithelium contain SC determinants. SC molecules may be synthesized in certain secretory cells of mucous membrane and glandular epithelium and the combining of SC with IgA could occur in the cytoplasm of epithelial cells, the intercellular spaces and/or in the lumens of glandular acini and ductules.

scholarly journals P305 A location-based prediction model in Crohn’s disease regarding a novel serological marker, anti-Chitinase 3-like 1 autoantibodies

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S305-S306
Author(s):  
N Sipeki ◽  
P Kovats ◽  
C Deutschmann ◽  
P Schierack ◽  
D Roggenbuck ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Serological Marker ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Course ◽  
Innate Immune Responses ◽  
Colonic Involvement ◽  
Underlying Mechanisms

Abstract Background A defective neutrophil regulation in IBD is thought to play an important role in the onset or manifestation of IBD, since it could lead to damage of the intestinal mucosal barrier by infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defence of the intestinal epithelium. Under normal conditions, IgA would contribute to the elimination of microbes, but in connection with the loss of tolerance to CHI3L1 in IBD, IgA could participate in the CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA auto-Abs to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. Methods We aim to determine the predictive potential of immunoglobulin subtypes of a novel serological marker, anti-chitinase 3-like 1 autoantibodies (aCHI3L1) regarding determination of disease phenotype, therapeutic strategy and long-term disease course in a prospective referral adult IBD patient cohort. Immunoblotting of antineutrophil-cytoplasmic antibody-positive sera of IBD patients on neutrophil proteins and MALDI-TOF mass spectrometry were used to identify autoantigenic targets in IBD. Sera of 257 CD and 180 UC patients were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1 along with 86 healthy controls (HCONT). Results IgA type was more prevalent in CD than UC (29.2 vs. 11.1%) or HCONT (2.83%; p &lt; 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC compared with HCONT (39.3 and 32.8 vs. 4.65%, respectively; p &lt; 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (p &lt; 0.0001 and p = 0.038, respectively) in CD. Complicated disease behaviour at sample procurement was associated with the presence of aCHI3L1 sIgA positivity (57.1% vs. 36.0%, p = 0.009). Whilst, IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in CD (46.9% vs. 25.7%, p = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of the diagnosis, positivity for IgA or sIgA type aCH3L1 predicted a faster progression towards complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. Conclusion CHI3L1 is a novel neutrophil autoantigenic target in IBD. Consideration of antibody classes along with location-based prediction can revolutionise the future of serology in IBD.

scholarly journals Fecal Immunoglobulin A Antibodies in Dogs Infected or Vaccinated with Canine Coronavirus

2004 ◽  
Vol 11 (1) ◽  
pp. 102-105 ◽  
Author(s):  
Nicola Decaro ◽  
Annamaria Pratelli ◽  
Antonella Tinelli ◽  
Vito Martella ◽  
Michele Camero ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Immunoglobulin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inactivated Vaccine ◽  
Secretory Immunoglobulin A ◽  
Intramuscular Route ◽  
Degree Of Protection ◽  
Canine Coronavirus ◽  
Iga Antibodies ◽  
Secretory Immunoglobulin

ABSTRACT Fecal secretory immunoglobulin A (IgA) antibodies in dogs infected or vaccinated with canine coronavirus (CCV) were evaluated by an enzyme-linked immunosorbent assay. The study was carried out with 32 fecal samples collected just before inoculation and at 28 days postinoculation. Five groups were studied: naturally infected dogs, experimentally infected dogs, dogs inoculated with a modified live (ML) CCV vaccine by the intramuscular route, dogs inoculated with an ML CCV vaccine by the oronasal route, and dogs given an inactivated CCV vaccine. Both the naturally and the experimentally infected dogs developed high levels of fecal IgAs. Interestingly, dogs inoculated with the ML CCV vaccine by the oronasal route developed levels of fecal IgA that were higher than those observed in the dogs inoculated with the same CCV vaccine by the intramuscular route or those observed in dogs inoculated with the inactivated vaccine. A relationship between the level of fecal IgAs to CCV and the degree of protection against CCV infection was observed.

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