Antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, and specific IgE to food allergens in children with inflammatory bowel diseases

Differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD) is difficult in the initial phases in pediatric patients with inflammatory bowel diseases (IBD). This study was performed to determine the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) in IBD. ANCA were specified with regard to their antigenic specifity, significance to the diagnosis, and correlation of titer with the disease activity. The occurrence of food allergy was questioned, too. Serum samples from 44 children with UC (n = 23) or CD (n = 21) and from disease-control children (coeliac disease, n = 21) were analyzed for IgG ANCA, ANCA target antigens, IgA and IgG ASCA, and IgE to food allergens. Results show that ANCA occur more frequently in UC than in CD and disease-control (74, 24, and 10%, respectively). The presence of ANCA does not reflect disease activity. Antigenic specificity does not differ in any group. IgA-ASCA are found more often in patients with CD (76% versus 17% in UC). The testing for both ANCA and ASCA enabled clear-cut differential diagnosis between UC and CD based on the high specificity (ANCA+ ASCA- 92.5% for UC, ANCA- ASCA+ 93.2% for CD). Specific IgE to food allergens were found in 8.7, 14.3, and 23.8% of patients with UC, CD, and coeliac disease, respectively. We conclude that combined testing of ANCA and ASCA represents a valuable tool in the differential diagnosis between UC and CD in pediatric patients, minimizing invasive diagnostic procedures. Monitoring of ANCA, its specificity, and titer determination does not bring more information. Testing for specific IgE to food allergens may be considered in individual patients.     

炎症性肠病患者中四种自身抗体联合检测的临床意义

为探讨联合测定血清抗中性粒细胞胞浆抗体(ANCA)、抗酿酒酵母菌抗体(ASCA)、抗小肠杯状细胞抗体(IGA)、抗胰腺腺泡抗体(PAB)对溃疡性结肠炎(UC组)和克罗恩病(CD组)的诊断和鉴别诊断价值.用间接免疫荧光法测定20例UC组和20例CD组以及10例肠道疾病组患者和5名健康对照组血清ANCA、ASCA、IGA、PAB水平.在四个组中ANCA的阳性率分别为70%、25%、10%和0%,UC组显著高于后三组(P<0.05);而ASCA的阳性率分别为15%、60%、10%和0%,CD组显著高于其他三组(P<0.05).IGA阳性率分别为30%、65%、10%和0%,CD组亦显著高于二个对照组(P<0.05),但与uc组比较,无显著性差异(P>0.05).ANCA /ASCA-诊断UC的敏感性、特异性和阳性、阴性预测值分别是55%、90%、84.6%和66.7%,而ASCA /ANCA-的诊断CD分别是35%、95%、87.5%和59.4%.IGA /ANCA-的诊断cD分别是45%、95%、90%和63.3%;AN-CA、ASCA和IGA阳性有利于炎症性肠病(IBD)的诊断却不能敏感地筛选;ANCA、ASCA和IGA联合检测可作为UC和CD鉴别诊断,是IBD非创伤性鉴别诊断方法之一.     

Distribution and phylogenetic analysis of <Emphasis Type="Italic">Blastocystis</Emphasis> sp. subtypes isolated from IBD patients and healthy individuals in Iran

Blastocystis is a single-celled intestinal parasite commonly found in humans and a broad range of animals all over the world. In humans, its role in health and disease remains unsettled. The aim of our study was to investigate the distribution of Blastocystis and Blastocystis subtypes (ST) in patients with inflammatory bowel disease (IBD) and control subjects. A total of 71 stool samples were collected from IBD patients, 69 and 2 of whom had ulcerative colitis (UC) and Crohn’s Disease (CD), respectively. Moreover, 166 stool samples from healthy subjects were included as control samples. All stool samples were cultivated, and 550-bp fragments of the small subunit ribosomal RNA gene was amplified from Blastocystis-positive cultures. All PCR-positive samples were sequenced. Blastocystis was observed in 9 (12.67%) and 35 (21.1%) IBD patients and healthy controls, respectively. There was no statistically significant correlation between IBD and presence of Blastocystis (P = 0.147). There was a statistically significant correlation between age and Blastocystis colonization in the IBD group (P < 0.05), but not among healthy controls. No significant correlation between gender and colonization was observed. ST1 and ST3 were obtained from 1 (12.5%) and 7 (87.5%) IBD patients, respectively, while in the healthy control group, subtypes 1, 2, and 3 were found in 14 (40%), 12 (34.28%), and 9 (25.72%), respectively. Phylogenetic analysis showed no variation in the distribution of subtypes nor intra-subtype genetic diversity between samples acquired from IBD patients and healthy controls. This study showed a trend towards a lower prevalence of Blastocystis in IBD patients than in control subjects. ST3 sequences isolated from IBD patients and control individuals did not appear to differ genetically.     

Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease are associated with disease severity but not NOD2/CARD15 mutations

Anti-Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients [143 CD, 75 UC, 10 with indeterminate colitis (IC)] and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins (Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in-house enzyme-linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA-positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0.001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years (P < 0.0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.     

Are anti-neutrophil cytoplasmic antibodies (ANCA) clinically useful in inflammatory bowel disease (IBD)?

Since the first detection of ANCA in IBD, numerous studies have dealt with their prevalence, antigenic specificities, clinical significance, pathophysiological role, and their induction. This review summarizes the information obtained from those studies and shows that ANCA are not directly useful as diagnostic and prognostic factors in IBD. ANCA were detected in 50-85% of patients with ulcerative colitis (UC) and 10-20% of patients with Crohn's disease (CD). Multiple target antigens are recognized by these autoantibodies, including both cytoplasmic and nuclear proteins. A pathophysiological role for ANCA in IBD is far from clear. On the one hand, it is suggested that ANCA are genetic markers of susceptibility for IBD, and on the other hand, the induction of ANCA in those diseases may just be an epiphenomenon of chronic inflammation. We discuss recent evidence that ANCA may be induced by a break-through of tolerance towards bacterial antigens.     

Analysis of serum antibodies in patients suspected of having inflammatory bowel disease

Inflammatory bowel disease (IBD) is the general term used for a heterogeneous group of intestinal disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Serological markers such as anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophilic cytoplasmic antibody (atypical pANCA) have proven useful in the diagnosis and differentiation of CD and UC. Immunoglobulin A (IgA) antibody directed against the outer membrane protein C (OmpC) of Escherichia coli is said by one group to have clinical utility in diagnosing IBD, specifically in ASCA-negative CD patients. Our objective in this study was to compare the results obtained from two separate laboratories offering similar IBD tests using sera from suspected IBD patients. One hundred ninety-seven sera received for IBD testing were included in the study. The agreement between the two laboratories was 93.4% for ASCA IgA, 90.9% for ASCA IgG, and 87.8% for atypical pANCA IgG. There were 25 sera with ASCA-negative/OmpC-positive results reported by one laboratory. Thirteen of these 25 (52.0%) ASCA-negative/OmpC-positive sera were also atypical pANCA positive (9 as determined by both laboratories, 3 by one, and 1 by the other). Atypical pANCA antibody is found primarily in IBD patients with UC and colon-limited CD (Crohn's colitis). We conclude that the ASCA and atypical pANCA assays showed good agreement between the two laboratories, but the data for ASCA-negative/OmpC-positive sera suggest that many (52.0%) of these patients were more likely to have had UC or Crohn's colitis based on the presence of an atypical pANCA.     

Increased Fecal Levels of Chromogranin A, Chromogranin B, and Secretoneurin in Collagenous Colitis

Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.     

Differing Relationship of Psycho-Social Variables with Active Ulcerative Colitis or Crohn’s Disease

Purpose

How psycho-social variables affect the degree of disease activity in patients with ulcerative colitis (UC) or Crohn’s disease (CD) is incompletely understood. Therefore, we measured and compared the impact of psycho-social variables on the active disease state in UC and CD.

Method

One hundred and twenty-two UC and 305 CD patients with active disease completed questionnaires detailing their psychological symptoms, threatening experiences, disease-coping strategies, satisfaction with life, quality of life, and demographics.

Results

UC and CD patients were aged (mean, SD) 38.6?±?14.0 and 45.2?±?15.1 years, respectively. The psychological symptom index (median, IQR) was greater in UC 1.24 (0.8) than CD 0.9 (0.8), p?<?0.001. UC used more emotion-focused strategies, 24.5 (5.7) than CD, 23.0 (5.7), p?<?0.03; problem-focused strategies, 16.4 (4.5) vs. 15.4 (4.2), p?<?0.04; and dysfunctional strategies, 23.7 (5.7) vs. 22.0 (5.0), p?<?0.01. UC activity correlated with gender, age, economic status, psychological symptoms, threatening experiences, all coping strategies, satisfaction with life, and quality of life (p?<?0.02–0.001). CD activity correlated with economic status, psychological symptoms, threatening experiences, dysfunctional strategies, satisfaction with life, and quality of life (p?<?0.05–0.001). UC activity was predicted by psychological symptoms (9.1% variance), economic status (6.9%), problem-focused strategies (4.2%), and threatening experiences (1.3%); CD activity by threatening experiences (5% variance) and psychological symptoms (4%). In path analysis, psychological symptoms and problem-focused strategies mediated the effects of economic status, age, and threatening experiences on UC activity. In CD, the dominant pathway was threatening experiences impacting on psychological symptoms.

Conclusion

The impact of psycho-social variables on the active disease state differs between UC and CD, thus indicating a need for specifically tailored psychotherapies.

     

Reappraisal of antibodies against Saccharomyces cerevisiae (ASCA) as persistent biomarkers in quiescent Crohn’s disease

A clear correlation exists between microbiota and the dysregulation of the immune response in Inflammatory Bowel Diseases (IBD), which comprise Crohn’s disease (CD) and ulcerative colitis (UC). These unbalanced reactions also involve humoral responses, with antibodies against Saccharomyces cerevisiae. Thus, here we aimed to quantify IgA and IgG specific to S. cerevisiae (ASCA) in quiescent CD and UC, to correlate the production of these antibodies with patient’s inflammatory response and disease clinical presentation. Twenty-nine subjects (16?CD and 13 UC) and 45 healthy controls were enrolled in this study and had plasma samples tested for ASCA and cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α), besides clinical evaluation. IBD patients had increase IgA and IgG ASCA, especially those with colonic (L2) and fistulizing (B3) CD. Similarly, patients who dropped out the treatment had augmented ASCA, while IgG was reduced in those receiving sulfasalazine treatment. Furthermore, the quiescent CD patients had elevated IL-6 on plasma, especially in the absence of treatment, together with increased counter regulatory response of IL-10. There was a positive correlation between IgA and IgG on CD but not UC, as well as between IgA and TNF in total IBD patients. In addition, the levels of IgG x TNF, IgA x IL-10 and IgG x IL-10 were also correlated in CD, indicating that ASCA production may be influenced by the inflammatory response. Finally, we concluded that ASCA could be pointed as relevant biomarker of CD presentation and residual inflammation, even in clinical remission patients.     

Clinical significance and prevalence of anti-Saccharomyces cerevisiae antibody in Chinese patients with primary biliary cirrhosis

Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) and its prevalence in Chinese primary biliary cirrhosis (PBC) patients have not been characterized and therefore needs to be defined. Enzyme-linked immunosorbent assay was used to test ASCA in sera from 198 PBC patients, 85 patients with other liver diseases (OLD) and 35 health controls (HC). Indirect immunofluorescence was used to detect anti-mitochondrial antibodies (AMA) in PBC. Results showed that the frequency of ASCA in PBC, 29.8 %, was higher than other disease groups. And ASCA occurred more frequently in PBC patients with positive anti-gp210 than the negative ones. Also, ASCA was detected in 7 out of 15 PBC negative for AMA. Some liver-related biochemical indices and inflammatory indices were significantly higher in PBC patients with positive ASCA (p < 0.05). In conclusion, the prevalence of ASCA in Chinese PBC patients is 29.8 %. PBC patients with positive ASCA are associated with more severe liver injury, and ASCA-IgA might be related to disease activity of PBC.     

Cognitive-Behavioural Therapy for Inflammatory Bowel Disease: 24-Month Data from a Randomised Controlled Trial

Purpose

There is ongoing controversy on the effectiveness of psychotherapy in inflammatory bowel disease (IBD). In the few small studies, cognitive-behavioural therapy (CBT) has been shown to alleviate symptoms of anxiety or depression. However, there is little research on the impact of CBT on physical outcomes in IBD and no studies on long-term effectiveness of CBT.

Methods

The present two-arm pragmatic randomised controlled trial aimed to establish the impact of CBT on disease course after 24 months of observation. The study compared standard care plus CBT (+CBT) with standard care alone (SC). CBT was delivered over 10 weeks, face-to-face (F2F) or online (cCBT). The data were analysed using linear mixed-effects models.

Results

CBT did not significantly influence disease activity as measured by disease activity indices at 24 months (Crohn’s Disease Activity Index (CDAI), p?=?0.92; Simple Clinical Colitis Activity Index (SCCAI), p?=?0.88) or blood parameters (C-reactive protein (CRP), p?<?0.62; haemoglobin (Hb), p?=?0.77; platelet, p?=?0.64; white cell count (WCC), p?=?0.59) nor did CBT significantly affect mental health, coping or quality of life (all p?>?0.05).

Conclusions

Therefore, we conclude that CBT does not influence the course of IBD over 24 months. Given the high rate of attrition, particularly in the CBT group, future trials should consider a personalised approach to psychotherapy, perhaps combining online and one-to-one therapist time.

     

Catalase and α-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in large groups of patients with ulcerative colitis (UC) and Crohn's disease (CD). Apart from antibodies against lactoferrin and bactericidal/permeability-increasing protein (BPI), which have been reported before, antibodies against two novel granulocyte antigens were identified: antibodies against a 57/56-kD doublet were found in 38% of samples from UC patients and in 26% of samples from CD patients, whereas antibodies against a 47-kD protein were found in 10% of samples from UC patients and in 18% of samples from CD patients. Partial purification and amino acid sequence analysis identified the 57-kD protein as catalase and the 47-kD protein as α-enolase. This study is the first to report catalase and α-enolase as granulocyte antigens for autoantibodies in IBD.     

Infliximab Biosimilar (CT-P13; Infliximab-dyyb): A Review in Autoimmune Inflammatory Diseases

Infliximab biosimilar (CT-P13/infliximab-dyyb; Remsima^®, Inflectra^®) is approved in several countries for use in all indications for which reference infliximab (Remicade^®) is approved, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis. Clinical data contributing to the EU approval of infliximab biosimilar were obtained from two pivotal double-blind clinical trials in patients with AS (PLANETAS) or RA (PLANETRA). Infliximab biosimilar demonstrated equivalence to reference infliximab in terms of its pharmacokinetic profile in patients with AS, patients with RA, and in healthy volunteers, and in terms of its efficacy in patients with RA. Clinical response rates in patients with RA or AS were maintained over the longer term (up to 102 weeks). In addition, the efficacy of infliximab biosimilar in patients with RA or Crohn’s disease and ulcerative colitis [i.e. inflammatory bowel disease (IBD)] has been demonstrated in the real-world setting. Infliximab biosimilar was generally well tolerated, with a tolerability profile similar to that of reference infliximab. Switching from reference infliximab to infliximab biosimilar had no detrimental effect on efficacy, safety, or immunogenicity compared with continuous infliximab biosimilar therapy, according to the extensions of PLANETAS and PLANETRA, and real-world data in IBD. Current evidence therefore suggests that infliximab biosimilar is a useful alternative to reference infliximab in patients with autoimmune inflammatory diseases.     

PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis

Inflammatory bowel diseases (IBDs; both ulcerative colitis [UC] and Crohn’s colitis [CC]) are well-established predisposing pathological conditions for colorectal cancer (CRC) development. In IBDs, both the endoscopy and the histology assessment of CRC precursors (i.e., dysplasia, also defined as intraepithelial neoplasia) are associated with low interobserver consistency, and no reliable dysplasia-specific biomarker is available. The programmed cell death 4 (PDCD4) tumor suppressor gene is involved in sporadic colorectal oncogenesis, but scanty information is available on its involvement in IBD-associated colorectal oncogenesis. One hundred twenty tissue samples representative of active and inactive IBD and of flat dysplasia were obtained from 30 cases of UC and 30 of CC who undergone colectomy. Twenty additional biopsy samples obtained from patients with irritable bowel syndrome acted as normal controls. PDCD4 expression was assessed by immunohistochemistry; the expression of miR-21 (a major PDCD4 regulator) was investigated by quantitative real-time PCR and in situ hybridization in different series of a hundred samples. Tissue specimens from both controls and inactive IBD consistently featured strong PDCD4 nuclear immunostain; conversely, lower PDCD4 nuclear expression was featured by both active IBD and IBD-associated dysplastic lesions. Significant PDCD4 down-regulation distinguished IBD-associated dysplasia (p?<?0.001) versus active IBD. In both active IBD and dysplasia, PDCD4 down-regulation was significantly associated with miR-21 up-regulation. PDCD4 nuclear down-regulation (which parallels miR-21 up-regulation) is involved in the molecular pathway of IBD-associated carcinogenesis. PDCD4 nuclear expression may be usefully applied as ancillary maker in the histological assessment of IBD-associated dysplastic lesions.     

Review of Saccharomyces boulardii as a treatment option in IBD

Abstract

Context: Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn’s disease.

Objective: IBD is caused by an inappropriate immune response to gut microbiota. Treatment options could therefore be prebiotics, probiotics, antibiotics and/or fecal transplant. In this review, we have looked at the evidence for the yeast S. boulardii as a treatment option.

Material and methods: Searches in PubMed and the Cochrane Library with the MeSH words ‘Saccharomyces boulardii AND IBD’, ‘Saccharomyces boulardii AND Inflammatory Bowel Disease’, ‘Saccharomyces boulardii AND ulcerative colitis’ and ‘Saccharomyces boulardii AND Crohn’s disease’ gave total a total of 80 articles. After exclusions because of irrelevance, articles in other languages and some articles that were not available, 16 articles were included in this review.

Results: Three of the clinical trials showed a positive effect of S. boulardii in IBD patients (two Crohn’s disease, one ulcerative colitis), while there was one trial that didn’t prove any effect (Crohn’s disease). Included Animal trials and cell assays describes different anti-inflammatory mechanisms of S. boulardii supporting a possible effect when treating IBD patients.

Discussion: The number of studies of S. boulardii as treatment for IBD is limited. Furthermore, the existing trials have small populations and short duration.

Conclusion: We do not have enough evidence to prove the effect of S. boulardii in IBD. Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn’s disease are needed.     

Adalimumab: A Review of Its Use in the Treatment of Patients with Ulcerative Colitis

Adalimumab is a fully human, recombinant, monoclonal IgG1 antibody specific for the cytokine tumor necrosis factor-α. It is approved for the treatment of patients with inflammatory diseases, including adults with moderately to severely active ulcerative colitis who are refractory to, or intolerant of, corticosteroids and/or immunomodulators. In two well-designed 8- and 52-week clinical trials in patients with moderately to severely active ulcerative colitis despite treatment with corticosteroids and/or immunomodulators, subcutaneous adalimumab (160 mg, week 0; 80 mg, week 2; 40 mg every other week starting at week 4) was more effective than placebo for inducing and maintaining clinical remission. A statistically significant effect size (albeit <10 %) over placebo for the remission per Mayo score (primary endpoint) was observed with adalimumab at 8 weeks in both trials and at 52 weeks in one trial. Compared with placebo, adalimumab was associated with reductions in hospitalizations and improvements in other secondary endpoints, including clinical response, mucosal healing, corticosteroid-sparing, and health-related quality of life measures. Additionally, an early response to adalimumab was shown to be predictive of long-term efficacy. Adalimumab was generally well tolerated, compared with placebo, during clinical trials in patients with ulcerative colitis; the adverse event profile was similar to that in patients with Crohn’s disease or other approved indications. Adalimumab provides a new treatment option for patients with moderately to severely active ulcerative colitis who are refractory to, or intolerant of, corticosteroids and/or immunomodulators.     

Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease

Background

Immunoglobulin A (IgA) and IgG are major components in human intestinal mucosal surface and sera, and IgA- or IgG-coated bacteria play a vital role in the intestinal homeostasis. However, the correlation of IgA, IgG and their coated bacteria with the clinical characteristics of inflammatory bowel disease (IBD) has not been fully clarified.

Methods

The levels of soluble IgA and IgG in sera and feces were detected by ELISA, and the percentage of IgA- and IgG-coated bacteria in feces was analyzed by flow cytometry. Crohn’s disease activity index (CDAI) and Simple Endoscopic Score for Crohn’s disease (SES-CD) for Crohn’s disease (CD) or Mayo score and ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis (UC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the disease activity.

Results

178 patients with CD, 75 patients with UC and 41 healthy donors were recruited in this study. We found that the concentrations of soluble IgA and IgG in feces of active IBD patients were significantly higher than those in healthy controls and that the levels of soluble IgA and IgG in feces from IBD patients were positively correlated with CRP, ESR, Mayo score, UCEIS, SES-CD, and CDAI, respectively. Moreover, we also observed that the percentage of IgA- and IgG-coated bacteria markedly increased in feces of IBD patients, especially in CD patients at the age of 17 to 40 years old, with terminal ileal lesions and perianal lesions, as well as from E2 UC patients, and was closely associated with disease activities.

Conclusions

The levels of soluble IgA and IgG and the percentage of IgA- and IgG-coated bacteria strikingly increase in feces of IBD patients and correlate with disease activity.

     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

2020 international consensus on ANCA testing beyond systemic vasculitis

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.     

Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n?=?191) were positive by toxigenic culture and 61 % (n?=?129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p?<?0.0001). Forty percent of patients (n?=?85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p?<?0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p?=?0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p?=?0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR?=?1.1), intensive care unit treatment (OR?=?2.7), CI (OR?=?1.2), 027 CDI (OR?=?2.1), white blood cell count (OR?=?1.0), albumin level (OR?=?0.1), and stool toxin-positive 027 CDI (OR?=?2.5) were significantly associated with 100-day mortality (p?<?0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.