Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for in...Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity.However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/ MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient’s specific genetic background, thus improving on efficacy and safety rates.展开更多
In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-in...In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-individual differences in their efficacy and side effects have been reported.The effectiveness of these drugs is indeed very variable and side effects,particularly severe in pediatric patients,are common and often unpredictable:the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability.In this context,microRNAs(miRNAs)represent a new and promising field of research.miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level,and are fine-tuning regulators of diverse biological processes,including the development and function of the immune system,apoptosis,metabolism and inflammation.Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases,such as IBD.There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response;however,the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study.The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis,represents an important innovative approach that could be translated into clinical practice.In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs,and their potential role as molecular markers useful for predicting in advance GC response.展开更多
AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate(5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase(NAT) 1 and 2. METHODS: Concentrations...AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate(5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase(NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides(TGN) and methymercaptopurine nucleotides(MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients(3 females and 9 males, median age 16 years) with inflammatory bowel disease(6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines(7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase(ITPA) and thiopurine methyl transferase(TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 108 erythrocytes(range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations(absolutemean reduction 109 pmol/8 × 108 erythrocytes) was observed(median 221 pmol/8 × 108 erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration(P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study.展开更多
Takayasu’s arteritis(TA)and Crohn’s disease(CD)are two rare autoimmune disorders;however some reports describe the presence of both diseases in the same patient.This finding has suggested the possibility that both d...Takayasu’s arteritis(TA)and Crohn’s disease(CD)are two rare autoimmune disorders;however some reports describe the presence of both diseases in the same patient.This finding has suggested the possibility that both diseases could share some common etiologic origin.We describe a case of a 13-year-old male affected by CD characterized by fever,diarrhea,weight loss,abdominal pain and elevation of inflammatory markers.Clinical and histological features from colonic specimens were consistent with CD.Treatment with steroids and azathioprine was started,however disease flared every time steroids were tapered.One year later,while still on treatment,he came back to our attention for dyspnea at rest and at night,tiredness and weakness.At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit.A transthoracic echocardiography showed mild aortic valve insufficiency,left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch.A computed tomography scan showed abdominal aortathickening,dilated thoracic aorta and the presence of a thoracic aortic aneurysm.TA associated with CD was diagnosed and medical treatment with cyclophosphamide,steroids and aminosalicylic acid was started,with good clinical response at 6 mo follow-up.We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease.展开更多
Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease(IBD).In vivo it is active after reaction with reduced glutathione(GSH)and conversion to mercaptopurine.Although this react...Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease(IBD).In vivo it is active after reaction with reduced glutathione(GSH)and conversion to mercaptopurine.Although this reaction may occur spontaneously,the presence of isoforms M and A of the enzyme glutathione-S-transferase(GST)may increase its speed.Indeed,in pediatric patients with IBD,deletion of GST-M1,which determines reduced enzymatic activity,was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites.In addition to increase the activation of azathioprine to mercaptopurine,GSTs may contribute to azathioprine effects even by modulating GSH consumption,oxidative stress and apoptosis.Therefore,genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.reserved.展开更多
AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha...AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the disease.RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC.CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.展开更多
AIM To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide(MDP)-induced inflammation in Crohn's disease(CD) and ulcerative colitis(UC).METHODS Colonic mucosal biopsies were collected from...AIM To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide(MDP)-induced inflammation in Crohn's disease(CD) and ulcerative colitis(UC).METHODS Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments(in patients with active disease) or from noninflamed mucosa [in patients in remission or in healthy controls(HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria(LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups. RESULTS We demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor(G-CSF), interleukin(IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence of LB. Only with the addition of antibiotics, likely reducing the contribution of LB, multivariate statistical analysis could identify the combination of measures of G-CSF, tumor necrosis factor alpha, IL4 and IL17 as a good discriminator between CD and UC.CONCLUSION We showed that the presence of LB or antibiotics can significantly influence the inflammatory response ex vivo in inflammatory bowel diseases.展开更多
Celiac disease (CD) is an autoimmune enteropathy character- ized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concent...Celiac disease (CD) is an autoimmune enteropathy character- ized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concentration of IgA serum anti- transglutaminase (anti-tTG) antibodies together with mucosal damage at intestinal biopsy.展开更多
文摘Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity.However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/ MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient’s specific genetic background, thus improving on efficacy and safety rates.
基金Supported by Italian Ministry of Health,No.44/GR-2010-2300447
文摘In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-individual differences in their efficacy and side effects have been reported.The effectiveness of these drugs is indeed very variable and side effects,particularly severe in pediatric patients,are common and often unpredictable:the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability.In this context,microRNAs(miRNAs)represent a new and promising field of research.miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level,and are fine-tuning regulators of diverse biological processes,including the development and function of the immune system,apoptosis,metabolism and inflammation.Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases,such as IBD.There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response;however,the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study.The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis,represents an important innovative approach that could be translated into clinical practice.In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs,and their potential role as molecular markers useful for predicting in advance GC response.
基金Supported by Italian Ministry of Health,and Fondazione Benefica Alberto e Kathleen Casali
文摘AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate(5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase(NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides(TGN) and methymercaptopurine nucleotides(MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients(3 females and 9 males, median age 16 years) with inflammatory bowel disease(6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines(7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase(ITPA) and thiopurine methyl transferase(TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 108 erythrocytes(range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations(absolutemean reduction 109 pmol/8 × 108 erythrocytes) was observed(median 221 pmol/8 × 108 erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration(P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study.
文摘Takayasu’s arteritis(TA)and Crohn’s disease(CD)are two rare autoimmune disorders;however some reports describe the presence of both diseases in the same patient.This finding has suggested the possibility that both diseases could share some common etiologic origin.We describe a case of a 13-year-old male affected by CD characterized by fever,diarrhea,weight loss,abdominal pain and elevation of inflammatory markers.Clinical and histological features from colonic specimens were consistent with CD.Treatment with steroids and azathioprine was started,however disease flared every time steroids were tapered.One year later,while still on treatment,he came back to our attention for dyspnea at rest and at night,tiredness and weakness.At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit.A transthoracic echocardiography showed mild aortic valve insufficiency,left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch.A computed tomography scan showed abdominal aortathickening,dilated thoracic aorta and the presence of a thoracic aortic aneurysm.TA associated with CD was diagnosed and medical treatment with cyclophosphamide,steroids and aminosalicylic acid was started,with good clinical response at 6 mo follow-up.We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease.
文摘Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease(IBD).In vivo it is active after reaction with reduced glutathione(GSH)and conversion to mercaptopurine.Although this reaction may occur spontaneously,the presence of isoforms M and A of the enzyme glutathione-S-transferase(GST)may increase its speed.Indeed,in pediatric patients with IBD,deletion of GST-M1,which determines reduced enzymatic activity,was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites.In addition to increase the activation of azathioprine to mercaptopurine,GSTs may contribute to azathioprine effects even by modulating GSH consumption,oxidative stress and apoptosis.Therefore,genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.reserved.
基金Supported by Institute for Maternal and Child Health,IRCCS"Burlo Garofolo",No.RC 03/2009
文摘AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the disease.RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC.CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.
基金Supported by Institute for Maternal and Child Health-IRCCS"Burlo Garofolo",No.RC 03/09
文摘AIM To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide(MDP)-induced inflammation in Crohn's disease(CD) and ulcerative colitis(UC).METHODS Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments(in patients with active disease) or from noninflamed mucosa [in patients in remission or in healthy controls(HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria(LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups. RESULTS We demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor(G-CSF), interleukin(IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence of LB. Only with the addition of antibiotics, likely reducing the contribution of LB, multivariate statistical analysis could identify the combination of measures of G-CSF, tumor necrosis factor alpha, IL4 and IL17 as a good discriminator between CD and UC.CONCLUSION We showed that the presence of LB or antibiotics can significantly influence the inflammatory response ex vivo in inflammatory bowel diseases.
文摘Celiac disease (CD) is an autoimmune enteropathy character- ized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concentration of IgA serum anti- transglutaminase (anti-tTG) antibodies together with mucosal damage at intestinal biopsy.