Anti-pancreatic antibody in Turkish patients with inflammatory bowel disease and first-degree relatives

AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces cerevisiae (ASCA) were examined in serum samples of 214 subjects including patients with Crohn’s disease (CD, n = 64), ulcerative colitis (UC, n = 63), first-degree relatives of patients with CD (n = 25), first-degree relatives of patients with UC (n = 28),and a control group with gastrointestinal symptoms other than (IBD) (n = 34) by indirect immunofluorescence Positivity of PAB and ASCA was compared in terms of Vienna classification, disease activity and medications used.RESULTS: In terms of PAB positivity, no difference was found between patients with CD (14.1%) and UC (7.9%) however, significant difference was observed between patients with CD and subjects in the control group (P < 0.05). No difference was found between patients with CD and their relatives in terms of ASCA positivity, whereas a significant difference was found between other groups (P < 0.001). Compared to ASCA, the sensitivity of the PAB was 19% (7/37), its specificity was 93% (25/27), positive predictive value was 77% (7/9) and negative predictive value was 45% (25/55). ASCA was found with significantly higher prevalence in patients with CD activity index > 150 (P < 0.05).CONCLUSION: PAB is valuable in the diagnosis of IBD rather than CD, but cannot be used alone for diagnostic purposes. PAB is not superior to ASCA in CD diagnosis and in detecting CD among relatives of patients with CD.     

Familial occurrence of inflammatory bowel disease in Korea

BACKGROUND: Little information is available about the familial aggregation of inflammatory bowel disease (IBD) in Asian populations. We therefore determined the risk of familial aggregation of IBD among first-degree relatives of patients with ulcerative colitis (UC) or Crohn's disease (CD) in an ethnically distinct Korean population. METHODS: Familial aggregation of IBD was evaluated in terms of family history, prevalence, lifetime risk, and population relative risk in first-degree relatives of 1440 unrelated patients with UC (n = 1043) or CD (n = 397). RESULTS: A positive first-degree family history of IBD was observed in 27 probands (1.88%): 21 of 1043 (2.01%) with UC and 6 of 397 (1.51%) with CD. The crude prevalence of IBD in first-degree relatives of probands with IBD was 0.31%. The lifetime risk of IBD was 0.54% in all first-degree relatives of IBD probands, 0.52% in UC probands, and 0.67% in CD probands, with overall lifetime relative risks of 0.12% in parents, 0.79% in siblings, and 1.43% in offspring. The age- and sex-adjusted population relative risk of IBD was 13.8 in first-degree relatives of probands with IBD. CONCLUSIONS: Although a positive family history, prevalence, and lifetime risk of IBD among first-degree relatives of Korean IBD patients are much lower than among relatives of Western patients, the population relative risk in first-degree relatives is about equal in Koreans and Westerners. This finding indicates that a positive family history is an important risk factor for IBD in Koreans and in Westerners.     

Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease

OBJECTIVES: Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives. METHODS: A cohort of 1,670 individuals (570 CD, 173 UC, 165 healthy controls, 762 first-degree unaffected relatives of CD patients) was genotyped for Arg702Trp, Gly908Arg, and Leu1007fsinsC. Mutant allele and carrier frequencies were compared between groups. Segregation patterns were compared using a bivariate Dale model. RESULTS: The carrier prevalence of CARD15 variants for CD patients was 46.3%, compared to 20.6% for healthy controls and 22.0% for ulcerative colitis (UC) patients (both p < 0.0001). An increased carriage rate of CARD15 variants was observed in unaffected relatives of CD patients (37.3%; p < 0.0001 vs controls), although this was significantly lower than in the CD patients (p = 0.001). Paternal transmission gave a 5.17-fold higher chance for the child to develop the disease compared to maternal transmission (95% CI [1.59, 16.78]; p = 0.0063). UC patients belonging to mixed IBD families carried significantly more mutations (42.3%) compared to other UC patients (18.4%) (p < 0.01). CONCLUSIONS: Maternal transmission of the CARD15 variant allele is associated with a lower proportion of affected individuals compared to paternal transmission. Therefore, maternal transmission does not carry an increased risk of transmission as does paternal transmission. The increased mutation carriage in unaffected siblings of CD patients and in UC patients belonging to mixed families suggests that other factors than CARD15 contribute to the eventual disease expression.     

A comparative study of goblet cell and pancreatic exocine autoantibodies combined with ASCA and pANCA in Chinese and Caucasian patients with IBD

BACKGROUND: The incidence of Crohn's disease (CD) and ulcerative colitis (UC) is increasing, but differentiating between them is often extremely difficult. Pancreatic (PAB) and goblet cell autoantibodies (GAB) are specific for CD and UC, respectively, but with low sensitivity. In combination with anti-Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic antibodies (pANCA) testing, these antibodies may improve differentiation between the diseases. This study determined the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of PAB and GAB +/- ASCA and pANCA testing in Chinese and Caucasian IBD populations. RESULTS: Patients were recruited from Caucasian and Chinese populations (CD, n = 100; UC, n = 99; controls, n = 100). PAB was highly specific for CD, and detection was greater in patients less than 35 years old and in Chinese compared with Caucasian patients with CD (CD, 46% versus 22%, P = 0.018; UC, 2% versus 6%; controls, 0% versus 2%). GAB detection was poor in all groups (<2%). PAB showed a PPV of 93% to differentiate all patients with CD from patients with UC, but only 62% for those with isolated colonic disease. The PPV of PAB increased to 100%, specificity was 100%, and sensitivity was 21% for isolated colonic disease when combined with pANCA and ASCA. PAB expression was not associated with stricturing or perforating CD. CONCLUSIONS: This study identified that GAB was not useful in our patients with IBD. PAB expression was highly specific for CD and more sensitive in Chinese than Caucasian patients with CD. The combination of PAB, pANCA, and ASCA testing improved the differentiation between UC and CD, particularly in isolated colonic disease, compared with pANCA and ASCA testing alone.     

Cigarette smoking and age at diagnosis of inflammatory bowel disease

OBJECTIVES: The incidence and age of onset of inflammatory bowel disease (IBD) appear to be changing. The aim of this study was to determine whether the prevalence of cigarette smoking differs among patients with Crohn's disease (CD) or ulcerative colitis (UC) at the time of diagnosis compared with the general population and whether smoking history is related to the type and age of IBD onset. METHODS: Prevalence rates of smoking at the time of IBD diagnosis were compared between patients with CD and UC from the IBD Center at the University of Pittsburgh Medical Center versus age-, gender-, and time period-adjusted rates in the Pennsylvania general population. Analyses also were stratified by gender and diagnoses before and after 40 years of age, i.e., early and late onset. RESULTS: There were 263 IBD patients (144 UC patients and 119 CD patients) seen in the IBD center between August 2000 and December 2002. The prevalence of active smoking was significantly higher at diagnosis in CD patients compared with the Pennsylvania general population (33% versus 24%, P = 0.04), particularly in those with CD onset at 40 years of age or later (47% versus 27%, P = 0.005). In contrast, smoking prevalence was significantly lower in UC patients than the general population (9% versus 28%, P < 0.0001), particularly among those with UC onset before the age of 40 years (6% versus 27%, P < 0.0001). Smoking cessation was associated with an approximate, but nonsignificant, 3-fold higher likelihood of late-onset UC compared with CD. CONCLUSIONS: Cigarette smoking is associated with the development of late-onset CD and is protective against developing UC at any age, particularly early onset. Former smoking is associated with a high likelihood of developing late-onset UC, but not CD.     

Familial and Sporadic Inflammatory Bowel Disease: Comparison of Clinical Features and Serological Markers in a Genetically Homogeneous Population

Background: The familial occurrence of inflammatory bowel disease (IBD) and the clinical features of familial and sporadic IBD in the genetically homogeneous Finnish population are evaluated. Methods: 257 patients with Crohn disease (CD) and 436 with ulcerative colitis (UC) participated in the study. They were asked whether IBD was present (familial IBD) or absent (sporadic IBD) in their first-degree relatives. Data on the clinical course of the disease were collected from the patient records. Antibodies to Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) were determined from serum samples. Results: Affected first-degree relatives were found in 15.6% of patients with CD and in 13.8% of patients with UC. In familial cases, CD was more often located in the ileum (38% versus 21%) and less often in the ileocolon (35% versus 50%) ( P < 0.05) than in sporadic cases. A greater percentage of CD patients than UC patients were smokers (47% versus 13%; P < 0.01). An elevated level of IgA and/or IgG antibodies for ASCA was found more often in CD patients than in UC patients (59% versus 14%; P < 0.01), while pANCA were found more often in UC than in CD patients (48% versus 12%; P < 0.01). The combination of pANCA-ASCA + yielded a sensitivity, specificity and positive predictive value of 48%, 92% and 90%, respectively, for CD, and the combination of pANCA + ASCAof 55%, 94% and 90%, respectively, for UC. Conclusions: The percentage of familial IBD cases in Finland is comparable to that reported elsewhere in Europe. No important clinical differences between patients with familial and sporadic forms of the disease were found. ASCA is associated with both familial and sporadic CD and pANCA with UC, but low sensitivity diminishes their value as a serological marker of IBD or as a differential diagnostic test between CD and UC.     

Familial and sporadic inflammatory bowel disease: comparison of clinical features and serological markers in a genetically homogeneous population

BACKGROUND: The familial occurrence of inflammatory bowel disease (IBD) and the clinical features of familial and sporadic IBD in the genetically homogeneous Finnish population are evaluated. METHODS: 257 patients with Crohn disease (CD) and 436 with ulcerative colitis (UC) participated in the study. They were asked whether IBD was present (familial IBD) or absent (sporadic IBD) in their first-degree relatives. Data on the clinical course of the disease were collected from the patient records. Antibodies to Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) were determined from serum samples. RESULTS: Affected first-degree relatives were found in 15.6% of patients with CD and in 13.8% of patients with UC. In familial cases CD was more often located in the ileum (38% versus 21%) and less often in the ileocolon (35% versus 50%) (P< 0.05) than in sporadic cases. A greater percentage of CD patients than UC patients were smokers (47% versus 13%; P < 0.01). An elevated level of IgA and/or IgG antibodies for ASCA was found more often in CD patients than in UC patients (59% versus 14%; P < 0.01), while pANCA were found more often in UC than in CD patients (48% versus 12%; P < 0.01). The combination of pANCA-ASCA+ yielded a sensitivity, specificity and positive predictive value of 48%, 92% and 90%, respectively, for CD, and the combination of pANCA + ASCA- of 55%, 94% and 90%, respectively, for UC. CONCLUSIONS: The percentage of familial IBD cases in Finland is comparable to that reported elsewhere in Europe. No important clinical differences between patients with familial and sporadic forms of the disease were found. ASCA is associated with both familial and sporadic CD and pANCA with UC, but low sensitivity diminishes their value as a serological marker of IBD or as a differential diagnostic test between CD and UC.     

炎症性肠病并发低骨量/骨质疏松的危险因素分析

目的 对炎症性肠病(IBD)患者的骨密度状况进行评估,探讨其下降的危险因素.方法 通过对IBD患者血液学指标、身高、体重及腰椎骨密度进行测量,并与健康志愿者比较,分析IBD患者骨质疏松的危险因素.结果 共收集克罗恩病(CD)77例,溃疡性结肠炎(UC)43例,37例健康志愿者作为对照组.CD组、UC组及对照组的腰椎骨质的T值分别为-1.72±1.20、-1.26±1.12和-0.62±0.87,CD组的T值低于UC组(P=0.045)和对照组(P=0.000),UC组T值低于对照组(P=0.014).CD组、UC组及对照组的腰椎骨质疏松的发生率分别为23.3%、14.0%和0;CD组的腰椎骨质疏松发生率高于对照组,差异有统计学意义(P=0.003);UC组的腰椎骨质疏松发生率有高于对照组的趋势,但差异无统计学意义(P=0.053).多元回归分析显示,低体重(BMI≤18.4kg/m~2)是CD(OR=11.25,95%CI 3.198～39.580,P=0.000)和UC(OR=14.50,95%CI 1.058～88.200,P=0.045)患者骨质疏松的危险因素.年龄、病程、病变部位、CD活动指数(CDAI)、服用糖皮质激素、服用免疫抑制剂、血清25-羟基维生素D浓度等因素与骨质疏松的发生无相关性.结论 骨密度下降的发生在IBD患者中较为普遍,低体重是IBD患者骨质丢失的危险因素.     

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.     

Association of MALTectomy (appendectomy and tonsillectomy) and inflammatory bowel disease: a familial case-control study.

There is some controversy regarding the prevalence of tonsillectomy and appendectomy among patients with Crohn's disease (CD) and a lower rate of appendectomy among patients with ulcerative colitis (UC). However, some environmental and familial factors that could alter those figures have not been studied. OBJECTIVE: To explore the prevalence of MALTectomy (appendectomy and tonsillectomy) among patients with IBD, stressing those factors that may be significantly associated to it. METHOD: Age-and-sex matched case-control study in patients with IBD, their relatives and the general population. Two hundred and eighty seven cases were IBD patients (153 UC, and 134 CD), the "family control" group included 203 siblings and the population-based control group included 570 individuals. Potential confounding factors, such as smoking, educational level, oral contraceptive use, place of birth and residence up to the age of 15 years, were ruled out. RESULTS: Appendectomy and UC: 7% of UC patients had undergone appendectomy versus 20% (OR: 0.23; 95% CI: 0.11-0.5; p < 0.0001) of controls. Appendectomy rates in families with at least one case of UC were 17/153 (6.3%) and 61/306 (20%) in the control group (p < 0.001). Appendectomy and CD: Twelve per cent of CD patients had undergone appendectomy six months before the onset of the disease versus 17% among the control population (OR: 0.43; 95% CI: 0.29-0.95; p < 0.01). The frequency of appendectomy in families with at least one case of CD was 22/221 (10%), which was significantly lower (p < 0.05) than among the control group 45/264 (17%). No differences were found between IBD patients and familial controls. Tonsillectomy and CD: Forty six per cent of CD patients had undergone tonsillectomy versus 39% of control patients (OR: 1.77; 95% CI: 0.92-2.05; p = ns). Tonsillectomy and UC: Twenty eight per cent of UC patients had undergone tonsillectomy versus 39% of the population control group (OR: 1.07; 95 CI: 0.57-1.25: p = ns). In fact, no differences were found regarding the prevalence of tonsillectomies within families with IBD cases as compared to population controls. CONCLUSIONS: Appendectomy is not only less frequent among CD and UC patients, but also among their relatives, thus suggesting the existence of environmental and genetic factors with opposed etiological roles in IBD and appendicitis.     

Studies of Isolated Parietal and Enterochromaffin-Like Cells from the Rat

Background: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. Methods: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC), 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. Results: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years; P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. Conclusions: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor?

BACKGROUND: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. METHODS: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC). 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. RESULTS: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years: P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. CONCLUSIONS: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect.     

Relationship between CARD15, SLC22A4/5, and DLG5 polymorphisms and early-onset inflammatory bowel diseases: an Italian multicentric study

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with several polymorphisms in genes likely involved in innate immune responses and integrity of epithelial mucosal barrier. A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility. METHODS: We analyzed a panel of 6 polymorphisms within these genes in 227 Italian early-onset IBD patients (134 CD, 93 ulcerative colitis [UC]; age at diagnosis 相似文献   

Inflammatory bowel disease serology in Asia and the West

AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences.     

Role of the PXR gene locus in inflammatory bowel diseases

BACKGROUND: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population.METHODS: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls.RESULTS: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005).CONCLUSIONS: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.     

Nutritional status of children with inflammatory bowel disease in Saudi Arabia

AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease(IBD) in Saudi Arabia.METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn’s disease(CD) and ulcerative colitis(UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index(BMI) of each child [weight(kg)/height~2(m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and <-2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older.RESULTS: There were 374 children from 0.33 to 17 years of age, including 119(32%) children with UC and 255(68%) with CD. All of the children were Saudi nationals, and 68(57%) of the UC and 150(59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30(25%) patients with UC and 99(39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC(P = 0.037) only in the age group of 10-17 years(P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years(P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care.     

Are there any differences in phenotype or disease course between familial and sporadic cases of inflammatory bowel disease? Results of a population-based follow-up study

BACKGROUND: The influence of familial IBD on phenotype and course of disease in patients with CD and UC has not been studied in population-based cohorts. AIM: To compare phenotype and course of disease between IBD patients with a first-degree relative with IBD and sporadic cases in a population-based cohort followed prospectively for 5 yr. METHODS: Family history of IBD was registered at diagnosis and after 1 and 5 yr. Phenotype and course of disease were compared between sporadic and familial cases. RESULTS: Data for 200 patients with CD and 454 with UC were sufficient for analysis. A first-degree relative with IBD was registered in 14.5% of CD patients and 10.1% of UC patients. The concordance for type of disease was 82% and 70% for CD and UC, respectively. No differences between familial and sporadic cases as regards localization and behavior of disease in CD patients or disease extent in UC patients were observed. In CD patients with colonic involvement, those in the familial group were significantly younger at diagnosis than the sporadic cases. No difference in disease severity in CD patients was observed between the familial and sporadic groups. In UC patients relapse was more frequent in familial cases, but no difference was observed in the need for surgery or medical treatment. CONCLUSIONS: A family history of IBD does not seem to influence phenotype or to be an important prognostic factor for disease course in IBD patients.     

Evidence for a genetic defect in oral tolerance induction in inflammatory bowel disease

BACKGROUND: Previous studies have suggested that there may be a defect in the control of immune responses locally in the intestines of patients with inflammatory bowel disease (IBD). Recently, we documented a failure to induce oral tolerance to a fed soluble protein antigen, keyhole limpet hemocyanin (KLH), in IBD patients. Both Crohn's disease (CD) and ulcerative colitis (UC) appear to be multigenic disorders with evidence of familial segregation. In this study, we analyzed multiplex IBD families to determine whether the defect in oral tolerance induction is genetically regulated. METHODS: Patients and first-degree relatives from 6 multiplex families were fed KLH 50 mg on days 0 to 5 and 10 to 15, followed by subcutaneous immunizations on days 26 and 35. Blood was obtained and analyzed for KLH-specific T cell proliferative responses and cytokine production. Intestinal permeability was also assessed. RESULTS: In contrast to normal controls, all IBD patients, save 1 (10 patients out of 11 tested P<.0001 versus normal controls), failed to develop oral tolerance to KLH. Furthermore, in 3 of the 4 CD families, at least 1 unaffected family member (total of 5/14 unaffected individuals, P=.002 versus normal controls) also failed to tolerize. This is in sharp contrast to unaffected individuals with no family history of IBD (1/31 tested to date). CONCLUSIONS: This failure of tolerance induction could not be attributed to increased intestinal permeability. In the UC families, the defect in tolerance segregated with disease. These data support a genetic defect in tolerance induction in CD.     

Abnormalities of uterine cervix in women with inflammatory bowel disease

INTRODUCTION Cervical cancer is responsible for almost 4000 deaths annually in the United States[1]. Due in large part to mass screening protocols with papanicolaou (Pap) smears, mortality from cervical cancer has declined by over 70% in the past 50 years…