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

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 < 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 < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (p < 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.

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

Infection and Immunity ◽

10.1128/iai.68.7.3830-3839.2000 ◽

2000 ◽

Vol 68 (7) ◽

pp. 3830-3839 ◽

Cited By ~ 34

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.

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

Food & Function ◽

10.1039/d1fo02517a ◽

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.

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P288 Gut barrier failure biomarkers in IBD: Is there anything new beyond „The Wall’?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.417 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S296-S296

Author(s):

N Sipeki ◽

P Kovats ◽

B Balogh ◽

Z Shums ◽

G L Norman ◽

...

Keyword(s):

Cox Regression ◽

Mucosal Damage ◽

Mucosal Barrier ◽

Mucosal Inflammation ◽

Enzyme Linked Immunosorbent Assay ◽

Disease Course ◽

Barrier Dysfunction ◽

Gut Barrier ◽

Fatty Acid Binding ◽

Cox Regression Analysis

Abstract Background Several defects in the many specialised components of mucosal barrier have been reported in inflammatory bowel disease (IBD). These alterations may represent a primary dysfunction in Crohn’s disease(CD), but they may also perpetuate chronic mucosal inflammation in ulcerative colitis(UC). Changes in intestinal permeability can predict IBD course. Methods We aim to determine the predictive potential of a panel of serological markers that reflect either mechanical or immunological gut barrier dysfunction regarding determination of disease phenotype, therapeutic strategy and long-term disease course in a prospective referral adult IBD patient cohort. Sera of 266 CD (m/f:112/154, median age:25 years, B1:80.1%, P1:18.0%) and 187 UC (m/f:86/101, median age:33 years, extensive colitis:28.3%) patients were assayed for intestinal fatty acid-binding protein(I-FABP) and various immunoglobulin A (IgA) molecules, anti-F-actin[AAA IgA/IgG] and anti-gliadin[AGA IgA/IgG]) by enzyme-linked immunosorbent assay (ELISA) along with 155 healthy controls (HCONT). Clinical data were available on unfavourable disease outcome as well as disease activity and medical treatment during the prospective follow-up (median: 143 and 135 mths for CD and UC respectively). Results In UC, median I-FABP level was significantly lower than in HCONT(177.2 vs. 244.3 pg/ml; p < 0.05). sIgA level was higher in both CD and UC compared with HCONT(51.2 and 46.0 vs. 29.2 μg/ml; p < 0.0001). AAA positivity with IgA type predominance was significantly higher in CD(40.2vs UC:15.7; HCONT:6.2%). AGA was also more prevalent in CD(16.5vs UC:6.7; HCONT:7.2%). There was an association between the presence of IgA type AAA or AGA and antimicrobial antibodies. ACA IgA was also more prevalent in case of AAA IgA positivity(52.9 vs. 32.7%, p = 0.009). PS/PT IgA positivity was higher in AGA IgA positive patients (33.3 vs. 7.6%, p = 0.001). Complicated disease behaviour at sample procurement was associated with the presence of AAA and AGA IgA positivity. In Kaplan–Meier analysis concomitant presence of IgA and IgG type AAA was associated with a shorter time to resective surgery (HR[95% CI]: 2.03[1.06–3.90]) along with a higher risk of a second surgery needed (HR[95% CI]: 2.82[1.14–6.98]). Sensitivity analysis showed that the later remained significant in B1 patients (p = 0.002) and also remained independent predictor in multivariate Cox-regression analysis comprising relevant clinical factors(HR[95% CI]: 2.88[1.07–7.78], p = 0.037). Conclusion The presence of AAA and AGA reflects the ongoing mucosal damage in IBD rather than has a value in predicting the disease course.

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

Pharmacology ◽

10.1159/000520343 ◽

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

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

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A Controlled Clinical Study of the Effect of Nasal Immunization with a Streptococcus mutans Antigen Alone or Incorporated into Liposomes on Induction of Immune Responses

Infection and Immunity ◽

10.1128/iai.67.2.618-623.1999 ◽

1999 ◽

Vol 67 (2) ◽

pp. 618-623 ◽

Cited By ~ 46

Author(s):

Noel K. Childers ◽

Giang Tong ◽

Stephen Mitchell ◽

Katharine Kirk ◽

Michael W. Russell ◽

...

Keyword(s):

Immune Responses ◽

Streptococcus Mutans ◽

Immunoglobulin A ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Protein Vaccine ◽

Nasal Wash ◽

Immunization Strategies ◽

Iga Antibody ◽

Effective Use

ABSTRACT Recent attention to mucosal immunization strategies has been focused on the nasal route for vaccine delivery. This study was designed to determine the effectiveness of a liposome-protein vaccine compared to that of a protein-only vaccine in inducing immune responses in humans. Healthy subjects were randomly assigned to two groups and immunized intranasally with a crude antigen preparation rich in glucosyltransferase (C-GTF) from Streptococcus mutans, alone or in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals following immunization and were analyzed for anti-C-GTF activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A (IgA) anti-C-GTF activity in the nasal wash from both groups after immunization increased to a mean peak of fivefold over the baseline level on day 28. Salivary IgA anti-C-GTF responses were induced to a lesser extent. IgG and IgA anti-C-GTF responses in serum were detected on day 14. The IgA responses were predominantly of the IgA1 subclass. These results show that C-GTF vaccines were more effective in inducing a local secretory IgA antibody response than a salivary or serum response when they were given intranasally. The IgA1 anti-C-GTF response in nasal wash samples for liposomal antigen versus antigen only was the only response which was significantly different (P < 0.04). This suggests that the form of the antigen affects the magnitude of the local mucosal response but not that of a disseminated response. These results provide evidence for the effective use of a nasal protein vaccine in humans for the induction of mucosal and systemic responses.

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Dynamics of secretory IgA in patients with generalized chronic periodontitis

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2019.039 ◽

2019 ◽

pp. 45-47

Author(s):

T. I. Sashkina ◽

G. S. Runova ◽

A. I. Abdullaeva ◽

A. Yu. Bozhedomov ◽

I. V. Saldusova ◽

...

Keyword(s):

Chronic Periodontitis ◽

Oral Fluid ◽

Negative Impact ◽

Immunoglobulin A ◽

Secretory Iga ◽

Mucosal Barrier ◽

Therapeutic Procedures ◽

The Russian Federation ◽

Secretory Immunoglobulin

Generalized chronic periodontitis (GCP) is a widespread disease. It has a serious negative impact on the quality of a patient’s life, posing a challenge to dentists all over the world. At present, standard therapy regimens for GCP adopted in the Russian Federation do not account for the mucosal barrier state, which is determined by a number of various factors, including the levels of secretory immunoglobulin A (sIgA). In our study, we attempted to assess the functional state of the mucosal barrier in patients with GCP and to provide a rationale for using immunotherapy aimed at restoring the effective barrier function of the oral mucosa. SIgA concentrations, which served as an indicator of the mucosal barrier state, were measured with ELISA. We found that patients with GCP had significantly lower sIgA concentrations in the oral fluid in comparison with healthy individuals. Although therapeutic procedures did help to increase sIgA levels, they still were much lower after therapy than in healthy volunteers (54.6 ± 30.5 µg/ml vs 151.2 ± 105.2 µg/ml). Increased permeability of the mucosal barrier caused sIgA to leak into the peripheral blood serum, where its concentration grew from 0.21 ± 0.28 µg/ml to 0.35 ± 0.47 µg/ml during the treatment course, suggesting damage to the mucosal integrity. This fact needs to be accounted for when treating patients with GCP.

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Secretory Immunoglobulin a Antibodies to Respiratory Viruses in Middle Ear Effusionl of Chronic Otitis Media with Effusion

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348948409300117 ◽

1984 ◽

Vol 93 (1) ◽

pp. 73-75 ◽

Cited By ~ 9

Author(s):

Tatsuji Yamaguchi ◽

Tomoko Urasawa ◽

Akikatsu Kataura

Keyword(s):

Otitis Media ◽

Otitis Media With Effusion ◽

Immunoglobulin A ◽

Chronic Otitis Media ◽

Respiratory Viruses ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Antibody Activity ◽

Iga Antibodies

In order to obtain evidence that viral infection may be involved in chronic otitis media with effusion, an attempt was made to detect secretory IgA antibodies to respiratory viruses in the effusions. The enzyme-linked immunosorbent assay used with purified viral antigens was employed for detecting antibodies in this study. Secretory IgA antibodies against adenoviruses, respiratory syncytial, and parainfluenza type 2 viruses were demonstrated in 31 of 128 effusions (27 of 114 ears with chronic otitis media with effusions and 4 of 14 ears with blue eardrum conditions). The specificity of antibody activity to each virus was confirmed by an absorption test.

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Human Milk Antibodies Against SARS-CoV-2: A Longitudinal Follow-Up Study

Journal of Human Lactation ◽

10.1177/08903344211030171 ◽

2021 ◽

pp. 089033442110301

Author(s):

Hannah G. Juncker ◽

M. Romijn ◽

Veerle N. Loth ◽

Tom G. Caniels ◽

Christianne J.M. de Groot ◽

...

Keyword(s):

Human Milk ◽

Clinical Symptoms ◽

Immunoglobulin A ◽

Spike Protein ◽

Enzyme Linked Immunosorbent Assay ◽

Follow Up Study ◽

Lactating Mothers ◽

Milk Antibodies ◽

Over Time

Background: Human milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) following Coronavirus Disease 2019 (COVID-19). These antibodies may serve as protection against COVID-19 in infants. However, the evolution of these human milk antibodies over time is unclear. Research Aim: To elucidate the evolution of immunoglobulin A (IgA) against SARS-CoV-2 in human milk after a SARS-CoV-2 infection. Methods: This longitudinal follow-up study included lactating mothers ( N = 24) who had participated in the COVID MILK study. To assess the evolution of SARS-CoV-2 antibodies, serum and human milk samples were collected 14–143 days after the onset of clinical symptoms related to COVID-19. Enzyme-Linked ImmunoSorbent Assay was used to detect antibodies against the ectodomain of the SARS-CoV-2 spike protein. Results: SARS-CoV-2 antibodies remain present up to 5 months (143 days) in human milk after onset of COVID-19 symptoms. Overall, SARS-CoV-2 IgA in human milk seems to gradually decrease over time. Conclusion: Human milk from SARS-CoV-2 convalescent lactating mothers contains specific IgA antibodies against SARS-CoV-2 spike protein up to at least 5 months post-infection. Passive viral immunity can be transferred via human milk and may serve as protection for infants against COVID-19. Dutch Trial Register on May 1st, 2020, number: NL 8575, URL: https://www.trialregister.nl/trial/8575 .

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Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Clinical and Vaccine Immunology ◽

10.1128/cvi.05443-11 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1593-1596 ◽

Cited By ~ 15

Author(s):

Ravinder Kaur ◽

Thomas Kim ◽

Janet R. Casey ◽

Michael E. Pichichero

Keyword(s):

Middle Ear ◽

Acute Otitis Media ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Two Dimensional Gel Electrophoresis ◽

Middle Ear Fluid ◽

Iga Antibodies ◽

Iga Antibody ◽

Entire Array

ABSTRACTThe human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of 137 children were compared. The ratio of IgG to IgA in the MEF was significantly different (P< 0.008) compared to NW because IgA levels were higher and IgG levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with transudation to the MEF. Small amounts of secretory IgA were detected in MEF but the electrophoresis patterns of the entire array of IgA antibodies in the MEF and NW were virtually identical in each child evaluated; thus, IgA in MEF derived predominantly from serum and the nasopharynx by reflux via the Eustachian tube. The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody in the MEF and NW identifies the predominant source of antibody in the MEF as a transudate of serum combined with nasal secretions refluxed from the nasopharynx in children.

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Evaluation of the INOVA Diagnostics Enzyme-Linked Immunosorbent Assay Kits for Measuring Serum Immunoglobulin G (IgG) and IgA to Deamidated Gliadin Peptides

Clinical and Vaccine Immunology ◽

10.1128/cvi.13.1.150-151.2006 ◽

2006 ◽

Vol 13 (1) ◽

pp. 150-151 ◽

Cited By ~ 44

Author(s):

Harry E. Prince

Keyword(s):

Celiac Disease ◽

Immunosorbent Assay ◽

Immunoglobulin G ◽

Immunoglobulin A ◽

Serum Immunoglobulin ◽

Enzyme Linked Immunosorbent Assay ◽

Gliadin Antibodies ◽

Gliadin Peptides ◽

Disease Specific ◽

Inova Diagnostics

ABSTRACT New assays for antibodies to deamidated gliadin peptides (DGP) expressing celiac disease-specific epitopes were evaluated using 154 sera previously tested for endomysial immunoglobulin A (IgA) (EMA), transglutaminase IgA (TGA), and conventional gliadin antibodies. DGP antibody results showed 97% concordance with EMA and TGA results. Of 56 sera negative for EMA and TGA but positive for conventional gliadin antibodies, 54 (96%) were negative for DGP antibodies.

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