ABSTRACT
OBJECTIVES: Crohn's disease (CD) and Behçet's disease (BD) are two autoinflammatory diseases that share clinical and pathogenic features. Furthermore, when BD involves the gastrointestinal tract, it is extremely difficult to distinguish endoscopic lesions from CD lesions. HLA-B*51 allele expression is highly associated with BD diagnosis. In this study we analysed HLA-B*51 status in 70 Argentine patients with confirmed CD diagnosis and compared it to our previous Argentine BD cohort, with the aim of finding similarities or differences between these two diseases regarding HLA-B*51 status. METHODS: This is a multi-centre case-control study, including 70 patients with confirmed CD diagnosis, who underwent HLA-B*51 allele status testing; the results were compared to our previous BD cohort of 34 patients. RESULTS: Among patients with CD, 12.85% were positive for the HLA-B*51 allele, compared with 38.24% patients with BD (OR=0.238; 95% CI=0.089-0.637; p=0.004). CONCLUSIONS: Our finding suggests that determination of HLA-B*51 allele status may contribute to the differential diagnosis between CD and BD.
Subject(s)
Behcet Syndrome , Crohn Disease , Humans , Case-Control Studies , Crohn Disease/diagnosis , Crohn Disease/genetics , Alleles , HLA-B Antigens/genetics , Behcet Syndrome/diagnosis , Behcet Syndrome/genetics , HLA-B51 Antigen/geneticsABSTRACT
Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a ß-galactoside-binding protein, promotes homeostasis by reprogramming innate and adaptive immunity. Here, we identify a glycosylation-dependent "on-off" circuit driven by Gal1 and its glycosylated ligands that controls intestinal immunopathology by targeting activated CD8+ T cells and shaping the cytokine profile. In patients with inflammatory bowel disease (IBD), augmented Gal1 was associated with dysregulated expression of core 2 ß6-N-acetylglucosaminyltransferase 1 (C2GNT1) and α(2,6)-sialyltransferase 1 (ST6GAL1), glycosyltransferases responsible for creating or masking Gal1 ligands. Mice lacking Gal1 exhibited exacerbated colitis and augmented mucosal CD8+ T cell activation in response to 2,4,6-trinitrobenzenesulfonic acid; this phenotype was partially ameliorated by treatment with recombinant Gal1. While C2gnt1-/- mice exhibited aggravated colitis, St6gal1-/- mice showed attenuated inflammation. These effects were associated with intrinsic T cell glycosylation. Thus, Gal1 and its glycosylated ligands act to preserve intestinal homeostasis by recalibrating T cell immunity.
ABSTRACT
Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are immunologically mediated disorders. Several therapies are focused on activated T cells as key targets. Although Lactobacillus kefiri has shown anti-inflammatory effects in animal models, few studies were done using human mucosal T cells. The aim of this work was to investigate the immunomodulatory effects of this bacterium on intestinal T cells from patients with active IBD. Mucosal biopsies and surgical samples from IBD adult patients (n = 19) or healthy donors (HC; n = 5) were used. Lamina propria mononuclear cells were isolated by enzymatic tissue digestion, and entero-adhesive Escherichia coli-specific lamina propria T cells (LPTC) were expanded. The immunomodulatory properties of L. kefiri CIDCA 8348 strain were evaluated on biopsies and on anti-CD3/CD28-activated LPTC. Secreted cytokines were quantified by ELISA, and cell proliferation and viability were assessed by flow cytometry. We found that L. kefiri reduced spontaneous release of IL-6 and IL-8 from inflamed biopsies ex vivo. Activated LPTC from IBD patients showed low proliferative rates and reduced secretion of TNF-α, IL-6, IFN-γ and IL-13 in the presence of L. kefiri. In addition, L. kefiri induced an increased frequency of CD4+FOXP3+ LPTC along with high levels of IL-10. This is the first report showing an immunomodulatory effect of L. kefiri CIDCA 8348 on human intestinal cells from IBD patients. Understanding the mechanisms of interaction between probiotics and immune mucosal cells may open new avenues for treatment and prevention of IBD.
ABSTRACT
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing intestinal inflammation. Galectin-1 (Gal-1) is an endogenous lectin with key pro-resolving roles, including induction of T-cell apoptosis and secretion of immunosuppressive cytokines. Despite considerable progress, the relevance of Gal-1-induced T-cell death in inflamed tissue from human IBD patients has not been ascertained. Intestinal biopsies and surgical specimens from control patients (n = 52) and patients with active or inactive IBD (n = 97) were studied. Gal-1 expression was studied by RT-qPCR, immunoblotting, ELISA and immunohistochemistry. Gal-1-specific ligands and Gal-1-induced apoptosis of lamina propria (LP) T-cells were determined by TUNEL and flow cytometry. We found a transient expression of asialo core 1-O-glycans in LP T-cells from inflamed areas (p < 0.05) as revealed by flow cytometry using peanut agglutinin (PNA) binding and assessing dysregulation of the core-2 ß 1-6-N-acetylglucosaminyltransferase 1 (C2GNT1), an enzyme responsible for elongation of core 2 O-glycans. Consequently, Gal-1 binding was attenuated in CD3+CD4+ and CD3+CD8+ LP T-cells isolated from inflamed sites (p < 0.05). Incubation with recombinant Gal-1 induced apoptosis of LP CD3+ T-cells isolated from control subjects and non-inflamed areas of IBD patients (p < 0.05), but not from inflamed areas. In conclusion, our findings showed that transient regulation of the O-glycan profile during inflammation modulates Gal-1 binding and LP T-cell survival in IBD patients.
Subject(s)
Colitis, Ulcerative/pathology , Crohn Disease/pathology , Galectin 1/metabolism , Intestinal Mucosa/pathology , T-Lymphocytes/pathology , Adolescent , Adult , Aged , Apoptosis/drug effects , Cell Survival , Colitis, Ulcerative/metabolism , Crohn Disease/metabolism , Female , Humans , Inflammation , Intestinal Mucosa/metabolism , Ligands , Male , Middle Aged , Polysaccharides/chemistry , Polysaccharides/metabolism , T-Lymphocytes/metabolism , Young AdultSubject(s)
Inflammatory Bowel Diseases/genetics , Janus Kinase 2/genetics , Mutation , Thromboembolism/genetics , Adolescent , Adult , Argentina/epidemiology , Child , Child, Preschool , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/genetics , Crohn Disease/epidemiology , Crohn Disease/genetics , Female , Gene Expression Regulation , Humans , Incidence , Inflammatory Bowel Diseases/epidemiology , Male , Middle Aged , Risk Assessment , Sensitivity and Specificity , Thromboembolism/epidemiology , Young AdultABSTRACT
BACKGROUND AIMS: Anemia is a common complication of inflammatory bowel diseases (IBD) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation, ferric carboxymaltose (FeCarb), in comparison with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia (IDA) in IBD. METHODS: Two hundred patients were randomized in a 2:1 ratio (137 FeCarb:63 FeSulf) to receive FeCarb (maximum 1,000 mg iron per infusion) at 1-wk intervals until the patients' calculated total iron deficit was reached or FeSulf (100 mg b.i.d.) for 12 wk. The primary end point was change in hemoglobin (Hb) from baseline to week 12. RESULTS: The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). Response (defined as Hb increase of >2.0 g/dL) was higher for FeCarb at week 2 (P= 0.0051) and week 4 (P= 0.0346). Median ferritin increased from 5.0 to 323.5 mug/L at week 2, followed by a continuous decrease in the FeCarb group (43.5 mug/L at week 12). In the FeSulf group, a moderate increase from 6.5 to 28.5 mug/L at week 12 was observed. Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively. CONCLUSIONS: FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Ferric Compounds/administration & dosage , Ferrous Compounds/administration & dosage , Maltose/analogs & derivatives , Administration, Oral , Adult , Aged , Anemia, Iron-Deficiency/blood , Cohort Studies , Colitis, Ulcerative/blood , Crohn Disease/blood , Female , Ferric Compounds/adverse effects , Ferritins/blood , Ferrous Compounds/adverse effects , Germany , Hemoglobinometry , Humans , Infusions, Intravenous , Male , Maltose/administration & dosage , Maltose/adverse effects , Middle AgedABSTRACT
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
Subject(s)
Crohn Disease/diagnosis , Severity of Illness Index , Biomarkers/analysis , HumansABSTRACT
The gold standard to quantify Crohns disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
ABSTRACT
No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia. (AU)
Subject(s)
Humans , Crohn Disease/diagnosis , Severity of Illness Index , Biomarkers/analysisABSTRACT
No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia.
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
Subject(s)
Humans , Crohn Disease/diagnosis , Severity of Illness Index , Biomarkers/analysisABSTRACT
En el presente trabajo se analizan los aspectos salientes de la enfermedad celíaca del adulto. Se describen las formas clínicas de aparición y se remarcan las características monosintomáticas que pueden tener. Además, se resalta que puede llegarse al diagnóstico en cualquier momento de la vida de un individuo y que, en ocasiones, una complicación orienta hacia esta enfermedad. Llama la atención, en el seguimiento prolongado, el carácter cíclico que puede adoptar. Se puso especial énfasis en describir las influencias genéticas en relación con la enfermedad. Se describieron los resultados de una investigación con antígenos de histocompatibilidad HLA, llegándose a la conclusión de la mayor incidencia del HLA BB y HLA DR 3, sobre todo en pacientes con grupos sanguíneos A y D. Se comenta la efectividad del tratamiento sin gluten, aunque en ocasiones el uso de corticoides favorece la mejoría de los casos muy graves, con mala tolerancia de la alimentación oral. Se puso de manifiesto la variedad de complicaciones, concomitancias con otras enfermedades y la alarmante frecuencia de aparición de enfermedades malignas (linfoma y carcinoma). La probada relación de las mismas con la falta de cumplimiento del régimen sin gluten (en especial en carcinomas), fundamenta la postura de que el tratamiento dietético debe cumplirse en forma absoluta y de por vida. (AU)
Subject(s)
Humans , Male , Female , Adult , Celiac Disease/history , Celiac Disease/diagnosis , Celiac Disease/immunology , Celiac Disease/genetics , Celiac Disease/complications , Celiac Disease/therapy , Celiac Disease/diet therapy , Celiac Disease/drug therapy , Celiac Disease/mortality , Celiac Disease , Signs and Symptoms , Histocompatibility Antigens , Glutens , Lymphoma , Carcinoma , Metabolic Diseases , Hematologic Diseases , Gastrointestinal Diseases , Sexual Dysfunction, Physiological , Skin Manifestations , Calcium Metabolism Disorders , Adrenal Cortex Hormones/therapeutic useABSTRACT
En el presente trabajo se analizan los aspectos salientes de la enfermedad celíaca del adulto. Se describen las formas clínicas de aparición y se remarcan las características monosintomáticas que pueden tener. Además, se resalta que puede llegarse al diagnóstico en cualquier momento de la vida de un individuo y que, en ocasiones, una complicación orienta hacia esta enfermedad. Llama la atención, en el seguimiento prolongado, el carácter cíclico que puede adoptar. Se puso especial énfasis en describir las influencias genéticas en relación con la enfermedad. Se describieron los resultados de una investigación con antígenos de histocompatibilidad HLA, llegándose a la conclusión de la mayor incidencia del HLA BB y HLA DR 3, sobre todo en pacientes con grupos sanguíneos A y D. Se comenta la efectividad del tratamiento sin gluten, aunque en ocasiones el uso de corticoides favorece la mejoría de los casos muy graves, con mala tolerancia de la alimentación oral. Se puso de manifiesto la variedad de complicaciones, concomitancias con otras enfermedades y la alarmante frecuencia de aparición de enfermedades malignas (linfoma y carcinoma). La probada relación de las mismas con la falta de cumplimiento del régimen sin gluten (en especial en carcinomas), fundamenta la postura de que el tratamiento dietético debe cumplirse en forma absoluta y de por vida.