anti-Saccharomyces Cerevisiae Antibodies Research Articles

Mechanism of Sanhuang Decoction in alleviating dextran sulfate sodium induced ulcerative colitis in mice with Candida albicans colonization:based on high-throughput transcriptome sequencing

This study explored the mechanism of Sanhuang Decoction(SHD) in treating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice with Candida albicans(Ca) colonization via high-throughput transcriptome sequencing. Specifically, the animal model was established by oral administration of 3.0% DSS for 7 days followed by intragastrical administration of Ca suspension at 1.0 × 10~8 cells for 4 days and then the mice were treated with SHD enema for 7 days. Afterwards, the general signs were observed and the disease activity index(DAI) was recorded every day. After mice were sacrificed, colon length and colon mucosa damage index(CMDI) were determined and the histomorphology was observed with the HE staining method. The fungal loads of feces were detected with the plate method. Anti-saccharomyces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, and IL-6 in serum and colon were detected by ELISA. High-throughput RNA sequencing method was adopted to identify transcriptome of colon tissues from the control, model and SHD(15.0 g·kg~(-1)) groups. Differentially expressed genes(DEGs) among groups were screened and the GO and KEGG pathway enrichment analysis of the DEGs was performed. The expression levels of NLRP3, ASC, caspase-1, and IL-1β genes related to the NOD-like receptor signaling pathway which involved 9 DEGs, were examined by qRT-PCR and Western blot. The results demonstrated that SHD improved the general signs, decreased DAI and Ca loads of feaces, alleviated colon edema, erosion, and shortening, and lowered the content of β-1,3-glucan in serum and TNF-α, IL-1β, and IL-6 in serum and colon tissues of mice. Transcriptome sequencing revealed 383 DEGs between SHD and model groups, which were mainly involved in the biological processes of immune system, response to bacterium, and innate immune response. They were mainly enriched in the NOD-like signaling pathway, cytokine-cytokine interaction pathway, and retinol metabolism pathway. Moreover, SHD down-regulated the mRNA and protein levels of NLRP3, caspase-1, and IL-1β. In a word, SHD ameliorates DSS-induced UC in mice colonized with Ca, which probably relates to its regulation of NOD-like receptor signaling pathway.

The impact of comorbidity identification on outcomes in patients with pyoderma gangrenosum: A retrospective cohort study of previously hospitalized patients

The impact of comorbidity identification on outcomes in patients with pyoderma gangrenosum: A retrospective cohort study of previously hospitalized patients

Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study.

Backgrounds and AimsAPECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients’ clinical phenotype and gastrointestinal symptoms.MethodsDNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined.ResultsAnalysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms.ConclusionsGut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.

Anti-Microbial Antibody Response is Associated With Future Onset of Crohn’s Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk

Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDRs) of CD patients is an independent risk factor for future CD development. We measured host serum antibody response to 6 microbial antigens at enrollment (Prometheus enzyme-linked immunosorbent assay test: anti-Saccharomyces cerevisiae antibodies immunoglobulin A/immunoglobulin G, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). We used samples at enrollment of prospectively followed healthy FDRs from a nested case-control cohort of the Crohn's and Colitis Canada Genetics Environment Microbial Project. Those who later developed CD (n= 77) were matched 1:4 by age, sex, follow-up duration, and geographic location with control FDRs remaining healthy (n= 307). To address our research aims, we fitted a multivariable conditional logistic regression model and performed causal mediation analysis. High baseline AS (≥2) (43% of cases, 11% of controls) was associated with higher risk of developing CD (adjusted odds ratio, 6.5; 95% confidence interval, 3.4-12.7; P < .001). Importantly, this association remained significant when adjusted for markers of gut barrier function, fecal calprotectin, C-reactive protein, and CD-polygenic risk score, and in subjects recruited more than 3 years before diagnosis. Causal mediation analysis showed that the effect of high AS on future CD development is partially mediated (42%) via preclinical gut inflammation. Our results suggest that increased anti-microbial antibody responses are associated with risk of future development of CD, independent of biomarkers of abnormal gut barrier function, subclinical inflammation, and CD-related genetic risks. This suggests that anti-microbial antibody responses are an early predisease event in the development of CD.

Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review.

Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. This study is registered as PROSPERO CRD42016029363. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.

A Pilot Clinical Study on Post-Operative Recurrence Provides Biological Clues for a Role of Candida Yeasts and Fluconazole in Crohn's Disease.

Background and aims: This study prompted by growing evidence of the relationship between the yeast Candida albicans and Crohn’s disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD. Methods: Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ (n = 14) or placebo (n = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of C. albicans pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in C. albicans sensing and inflammation were also measured. Results: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti-C. albicans antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between C. albicans and CD. Conclusion: Several combinations of biomarkers of adaptive and innate immunity targeting C. albicans were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn’s Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.

ELISA validation approach for the detection of anti-saccharomyces cerevisiae antibodies in patients treated with biopharmaceutical heberprot-P®

This work describes the validation of an enzyme-linked immunosorbent assay (ELISA) for detection of anti-Saccharomyces cerevisiae antibodies (ASCA) in diabetic patients with foot ulcers, after the treatment with Heberprot-P®. Validation followed regulatory guidelines of US FDA and European Medicine Agency. Minimum required dilution of samples and quality controls were defined using pools of sera from diabetic patients and from healthy donors. Parameters such as cut point, specificity, precision, selectivity, robustness and sample stability were analyzed. The repeatability and intermediate precision percent ranged between 7.93-10.61% and 7.93-11.43 %, respectively, indicating low intra- and inter-assay variation. The specificity was proved by background noise suppression, reaching 100% of inhibition as strong criterion for the specificity of the immunoassay. The validated ELISA is a reliable tool for ASCA detection in human serum after the administration of Heberprot-P®, in order to find immunological reactions associated with latent contamination by host cell proteins from Saccharomyces cerevisiae.

Sodium houttuyfonate attenuates dextran sulfate sodium associated colitis precolonized withCandida albicansthrough inducing β-glucan exposure

Inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis is a chronic intestinal disease most likely associated with gut dysbiosis. Candida related mycobiota has been demonstrated to play a role in IBD progression. Traditional Chinese herbal medicines (TCHMs) with antifungal activity have a potential in prevention and treatment of fungi-related IBD. Sodium houttuyfonate (SH) is a promising anti-Candida TCHMs. In this study, a dextran sulfate sodium induced colitis model with Candida albicans precolonization is established. SH gavage can significantly decrease the fungal burdens in feces and colon tissues, reduce disease activity index score, elongate colon length, and attenuate colonic damages. Moreover, SH markedly inhibits the levels of anti-Saccharomyces cerevisiae antibodies, β-glucan, and proinflammatory cytokine (IL-1β, IL-6, IL-8, TNF-α), and increases anti-inflammatory factor IL-10 level in serum and colon tissue. Further experiments demonstrate that SH could induce β-glucan exposure, priming intestinal macrophages to get rid of colonized C. albicans through the collaboration of Dectin-1 and TLR2/4. With the decreased fungal burden, the protein levels of Dectin-1, TLR2, TLR4, and NF-κBp65 are fallen back, indicating the primed macrophages calm down and the colitis is alleviated. Collectively, these results manifest that SH can attenuate C. albicans associated colitis via β-glucan exposure, deepening our understanding of TCHMs in the prevention and treatment of fungi associated IBD.

Type one diabetes and autoimmune-related conditions: a Portuguese research in pediatric age

Background. Type 1 diabetes (T1D) is the most common chronic metabolic disease among children and the autoimmune process can induce the development of additional autoimmune diseases. We performed a retrospective study of the clinical records and analytical determinations of pediatric patients with T1D during a five-year-period. Methods. We identify 102 patients, similar gender distribution. In 98% was performed, at least, one tracking of other autoimmune disease. We found positive autoantibodies in 31%: thyroid antibodies (n = 16), antibodies for celiac disease (n = 10), and antinuclear antibodies (n = 5). Antibodies positivity occurred in mean 3.6 years after T1D diagnosis. Other conditions associated were pulmonary hemosiderosis, vitiligo, IgA deficit, uveitis, and positive Anti-Saccharomyces cerevisiae antibodies. Conclusions. Despite the antibodies’ positivity we highlight the possibility of other less common autoimmune-related conditions. The screening of comor-bidities is fundamental to perform an earlier diagnosis and prevent complications.

Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease.

Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.

Anti-Saccharomyces cerevisiae Antibody in Pediatric Crohn's Disease Patients without Mucosal Healing Is a Useful Marker of Mucosal Damage.

Background/AimsWe evaluated whether anti-Saccharomyces cerevisiae antibody (ASCA) titers are associated with diagnostic findings, disease activity, Paris classification phenotypes, and persistence after infliximab (IFX) treatment in children with Crohn’s disease (CD). We also investigated the role of ASCA as a predictor of mucosal healing (MH) and clinical remission (CR).MethodsThis study included 61 CD patients aged 19 years or younger who were diagnosed and treated between September 2010 and January 2019 and followed for at least 1 year. ASCA was regularly measured at the diagnosis of CD and at least 1 year after IFX therapy.ResultsThe average follow-up period was 3.8±3.4 years (range, 1.0 to 7.2 years). Regression analysis showed that the ASCA titer was the only factor associated with Simple Endoscopic Score for Crohn's Disease (SES-CD) or CR among all the parameters. In patients who had achieved MH (SES-CD=0), ASCA immunoglobulin G (IgG) was not associated with MH, but in patients without MH, ASCA IgG was associated with SES-CD (p=0.005) and CR (p<0.001). The cutoff value of ASCA IgG in patients with CR was 21.8 units. However, there was no difference in the relapse rate between the ASCA IgG-positive and -negative groups during the follow-up period.ConclusionsIn patients who have not achieved MH, ASCA IgG is closely related to mucosal damage and CR. Unlike Western studies, ASCA IgG may be more helpful in predicting prognosis than immunoglobulin A in Korean patients, but it is not an appropriate indicator to predict the relapse of CD. (Gut Liver 2021;15-770)

The diagnostic and prognostic value of serological markers of inflammatory bowel diseases (a literature review)

The diagnosis of inflammatory bowel disease (IBD) is based on a combination of clinical, endoscopic, histological, radiological and laboratory methods. However, conventional diagnostic methods are not always sufficiently informative in IBD, especially in the case of unclassified colitis, which necessitates the extension of standard diagnostic approaches. Currently, there is an actively search for non-invasive serological markers for early and differential diagnosis of IBD and for the assessment of activity and prognosis of Crohn's disease (CD) and ulcerative colitis (UC). Among the most interesting serological markers are anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), goblet cells antibodies (GAB) and pancreatic autoantibodies (PAB). The aim of this review is to assess the diagnostic and prognostic significance of ASCA, ANCA, GAB, PAB in CD and UC. The paper presents the summary of the data on the role of ASCA, ANCA, GAB and PAB in abnormalities of the immunological tolerance mechanisms to intestinal microflora and intestinal permeability in IBD. We discuss the results of the studies on the associations of ASCA with a complicated CD phenotype, its response to genetically engineered biological therapies, and the need for surgical intervention. The article describes the data on the association of ANCA to the risk of progression of left-sided UC to widespread (total) colon lesions resistant to hormonal therapy, and that of antibodies to DNA-lactoferrin complexes and proteinase 3 to primary sclerosing cholangitis. It has been noted that PAB may be a prognostic marker for ileocolitis, perianal lesions, extraintestinal manifestations and complicated CD, and GAB a predictor of total UC with chronic persistent course. It should be emphasized that combined determination of ASCA, ANCA, GAB and PAB is highly informative, compared to the isolated detection of autoantibodies, for the differential diagnosis and prognosis of CD and UC.

The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.

Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23–15.39) for AGA IgA and 3.08 (95% CI 1.19–7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.

Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA) Impair Neutrophil Candidacidal Activity and Are Increased in the Cellular Fraction of Vaginal Samples from Women with Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is primarily caused by Candida albicans and affects 75% of childbearing age women. Although C. albicans can colonize asymptomatically, disease is associated with an increased Candida burden, a loss of epithelial tolerance and a breakdown in vaginal microbiota homeostasis. VVC symptoms have been ascribed to a powerful inflammatory response associated with the infiltration of non-protective neutrophils (PMN). Here, we compared the immunological characteristics of vaginal fluids and cellular protein extracts obtained from 28 VVC women and from 23 healthy women colonized by Candida spp. We measured the levels of antibodies against fungal antigens and human autoantigens (anti-Saccharomyces cerevisiae antibodies (ASCA), C. albicans germ tube antibodies (CAGTAs) and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)), in addition to other immunological markers. Our results show that the pANCA levels detected in the cellular protein extracts from the vaginal fluids of symptomatic women were significantly higher than those obtained from healthy colonized women. Consistent with a potential physiologically relevant role for this pANCA, we found that specific anti-myeloperoxidase antibodies could completely neutralize the ex vivo killing capacity of polymorphonuclear cells. Collectively, this preliminary study suggests for the first time that pANCA are found in the pathogenic vaginal environment and can promptly impair neutrophil function against Candida, potentially preventing a protective response.

Meta-analysis of anti-Saccharomyces cerevisiae antibodies as diagnostic markers of Behçet’s disease with gastrointestinal involvement

ObjectiveDue to common exposure to yeast in the alcoholic and baking industry, positive rate of anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly high in patients with Behçet’s disease (BD) who have...

Predicting Outcomes in Pediatric Crohn’s Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease–Ahead Program

A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.

Assessment of clinical activity and severity using serum ANCA and ASCA antibodies in patients with ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) with unknown etiology. The lack of specific clinical manifestations, standard diagnostic criteria, objective and accurate indicators to the severity of the disease and the efficacy of the treatment, often results in difficulties in diagnosis and timely treatment of UC. Therefore, there is a need to develop a clinically suitable serum biomarker assay with high specificity and sensitivity.Objective and methodsTo explore the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-saccharomyces cerevisiae antibodies (ASCA) in the diagnosis, differential diagnosis and treatment assessment in patients with ulcerative colitis (UC). Serum levels of ANCA-IgG, ASCA-IgA and ASCA-IgG were measured by an enzyme-linked immunosorbent assay (ELISA) in 105 UC patients, 52 non-UC patients and 100 healthy controls.Results(1) Both the ANCA-IgG level and its positive rate in UC patients were significantly higher than those in non-UC controls and healthy controls (p < 0.01). However, the levels of ASCA-IgA, ASCA-IgG and the positive rates in UC patients had no statistical differences when compared with those in non-UC controls or healthy controls (p > 0.05). (2) The sensitivity of ANCA+ and ANCA+/ASCA− in detecting UC patients was 61.90% and 55.24%, respectively, whereas the specificity was 91.45% and 94.08%, respectively. The sensitivity of ASCA+ and ASCA+/ANCA− in non-UC disease controls was 5.33% and 3.85%, respectively, and specificity was 83.9% and 88.78%, respectively. (3) When UC patients were grouped into mild, moderate or severe subtypes, the ANCA-IgG levels were correlated with the severity of UC, and the differences of the ANCA-IgG levels were statistically different among the three subtypes (p < 0.05). There was no correlation between the levels of ANCA-IgG and the disease locations of UC.Conclusions(1) Serum levels of ANCA may be useful in the diagnosis of UC. (2) Dynamic quantitation of ANCA-IgG levels may be helpful in determining the severity of UC and therefore, may guide treatment of UC.

Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity.

Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity.

Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA.

Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) and compare them with these same antibodies in controls to determine whether a correlation between LPS and barrier proteins could be found. We obtained 94 ASCA- and 94 ANCA-positive blood samples, as well as 188 blood samples from healthy controls. Samples were assessed for antibodies to LPS, zonulin+occludin, S100B, and aquaporin-4 (AQP4). Results show significant elevation in antibodies in about 30% of ASCA- and ANCA-positive sera and demonstrate positive linear relationships between these antibodies. The findings suggest that individuals positive for ASCA and ANCA have increased odds of developing intestinal and BBB permeability compared to healthy subjects. The levels of LPS antibodies in both ASCA- and ANCA-positive and negative specimens showed from low and moderate to high correlation with antibodies to barrier proteins. This study shows that LPS, by damaging the gut and BBBs, contribute to the extra-intestinal manifestation of IBD. We conclude that IBD patients should be screened for LPS antibodies in an effort to detect or prevent possible barrier damage at the earliest stage possible to abrogate disease symptoms in IBS and associated disorders.

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa