You Did Not Teach Me What You Thought You Did Archambault Carlson, Marie
JAMA : the journal of the American Medical Association,
2019-Oct-22, Letnik:
322, Številka:
16
Journal Article
AIM： To evaluate fecal calprotectin （FC） as a surrogate marker of treatment outcome of relapse of inflammatory bowel disease （IBD） and, to compare FC with fecal myeloperoxidase （MPO） and fecal ...eosinophil protein X （EPX）.
METHODS： Thirty eight patients with IBD, comprising of 27 with ulcerative colitis （UC） and 11 with Crohn＇s disease （CD） were investigated before treatment （inclusion）, and after 4 and 8 wk of treatment. Treatment outcomes were evaluated by clinical features of disease activity and endoscopy in UC patients, and disease activity in CD patients. In addition, fecal samples were analyzed for FC by enzyme-linked immunosorbent assay （ELISA）, and for MPO and EPX with radioimmunoassay （RIA）.
RESULTS： At inclusion 37 of 38 （97%） patients had elevated FC levels （〉 94.7 μg/g）. At the end of the study, 31 of 38 （82%） patients fulfilled predefined criteria of a complete response IUC 21/27 （78%）; CD 10/11 （91%）. Overall, a normalised FC level at the end of the study predicted a complete response in 100% patients, whereas elevated FC level predicted incomplete response in 30%. Normalised MPO or EPX levels predicted a complete response in 100% and 90% of the patients, respectively. However, elevated MPO or EPX levels predicted incomplete response in 23% and 22%, respectively.
CONCLUSION： A normalised FC level has the potential to be used as a surrogate marker for successful treatment outcome in IBD patients. However, patients with persistent elevation of FC levels need further evaluation. FC and MPO provide superior discrimination than EPX in IBD treatment outcome.
CD14+CD33+ intestinal myeloid cells produce CCL11, which recruits eosinophils both in active and quiescent UC; levels of activated (CD66bhigh) eosinophils correlate with disease severity.
This study ...tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL‐5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL‐5 were determined by qRT‐PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66bhigh) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14+CD33+ cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14+CCL11+ mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL‐5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14+CD33+ myeloid cells, CCL11, and eosinophils in adult UC.
Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with ...inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.
Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).
Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.
Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.
Inflammatory bowel disease (IBD) is characterized by activation of both the innate and adaptive immune system in genetically susceptible individuals, resulting in chronic intestinal inflammation. The ...triggers that initiate and perpetuate this continuous inflammation are the subject of much speculation and research, although the central role of the intestinal microbiota is recognized, and is even a target for treatment in some circumstances. The mainstay of modern IBD treatment is suppression of the immune response towards as yet unspecified antigens, and conventional therapy includes corticosteroids, 5‐aminosalicylic acid (5‐ASA), thiopurines and methotrexate. Reducing activity of specific mediators has proven efficacious, including adhesion molecules, such as the gut‐homing integrin α4β7 expressed on the surface of circulating immune cells, and cytokines, such as tumour necrosis factor α (TNF‐α). This has been achieved using biologic agents including monoclonal antibodies. Recent discoveries in immunology and neuroscience have revealed that signals in the peripheral nervous system regulate inflammation, including levels of TNF‐α. The understanding of the mechanisms of the neuro‐immune communication involved in inflammation control in the gut is evolving, but is as yet incomplete. Clinical studies using implanted vagus nerve stimulators for treatment of IBD show encouraging results. Accordingly, the neural reflex control of inflammation is emerging as a potential therapeutic target in treatment of IBD. Here, we review current therapeutic options and neural reflex control of gut immunity in the context of intestinal inflammation.
ABSTRACT
We conducted a longitudinal‐biometric study examining stability and change in personality from ages 17 to 24 in a community sample of male and female twins. Using Tellegen's (in press) ...Multidimensional Personality Questionnaire (MPQ), facets of Negative Emotionality (NEM) declined substantially at the mean and individual levels, whereas facets of Constraint (CON) increased over time. Furthermore, individuals in late adolescence who were lowest on NEM and highest on CON remained the most stable over time, whereas those exhibiting the inverse profile (higher NEM, lower CON) changed the most in a direction towards growth and maturity. Analyses of gender differences yielded greater mean‐level increases over time for women as compared to men on facets of CON and greater mean‐level increases for men than women on facets of Agentic Positive Emotionality (PEM). Biometric analyses revealed rank‐order stability in personality to be largely genetic, with rank‐order change mediated by both the nonshared environment (and error) as well as genes. Findings correspond with prior evidence of a normative trend toward growth and maturity in personality during emerging adulthood.
Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a ...discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.Diagnostic blood-based biomarkers of pediatric IBD are limited. Here, the authors demonstrate a diagnostic lipidomic signature, comprising only of two molecular lipids. Translation of this signature into a scalable test has the potential to support clinical decision making.
Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs. IgG4-RD may show a variety of initial symptoms. In the oral mucosa, ...lesions present as inflammatory fibrosis with a large number of IgG4-positive plasma cells. Evaluating treatment is a well-known problem in IgG4-RD due to the absence of an established assessment system. There are difficulties in defining the severity of the disease, which is why treatment is primarily based on its clinical manifestations. We present a case report of localized IgG4-RD with ulcerative and proliferative manifestations on the tongue, which clinically mimicked oral squamous cell carcinoma. A tumor-like lesion on the tongue can indicate something else other than the malignant or reactive changes commonly found in the oral mucosa. Multiple differential diagnoses of these atypical oral lesions, including localized IgG4-RD, should be considered.
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