Search PubMed⌕ Search

Biomedical subjects

S Vermeire

Publications and source records attributed to S Vermeire.

At least 37 records · Page 2Linked to original sources
PubMed2004

Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab.

BACKGROUND: The role of tumour necrosis factor-alpha in the pathogenesis of inflammatory bowel disorders is well-known and is underscored by the effectiveness of antitumour necrosis factor-alpha treatment. Tumour necrosis factor-alpha exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci. AIMS AND METHODS: Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients. RESULTS: The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946). CONCLUSION: The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.

Adolescent↗
PubMed2004

The risk of post-operative complications associated with infliximab therapy for Crohn's disease: a controlled cohort study.

BACKGROUND: By temporarily suppressing the immune response, the anti-tumour necrosis factor agent, infliximab, may increase the risk of peri-operative complications. AIM: To test this hypothesis for intestinal resection in a cohort of 313 Crohn's disease patients treated with infliximab. Forty received one or more infusions prior to intestinal resection (31/40 within 12 weeks). METHODS: The post-operative events of these patients were compared with those of a control group (infliximab naive) of 39 patients adjusted for age, gender and surgical procedure. Early (10 days) and late (3 months) major or minor complications were identified. RESULTS: The incidence of early minor (15.0% vs. 12.8%) and major (12.5% vs. 7.7%) and late minor (2.5% vs. 5.1%) and major (17.5% vs. 12.8%) complications and the mean hospital stay after surgery (10.3 +/- 4.0 days vs. 9.9 +/- 5.5 days) were similar in both groups. A trend towards an increased early infection rate was found in infliximab pre-treated patients (6 vs. 1; P = 0.10), but more patients in this group received corticosteroids and/or immunosuppressives (29 vs. 16 patients; P < 0.05). CONCLUSION: The use of infliximab before intestinal resection does not prolong the hospital stay and does not increase the rate of post-operative complications.

Adolescent↗
PubMed2004

Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease.

AIM: To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcgammaRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody-dependent cell-mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non-Hodgkin's lymphomas) and response to infliximab in Crohn's disease. METHODS: FCGR3A-158 polymorphism was determined using an allele-specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C-reactive protein levels) were assessed in 200 and 145 patients, respectively. RESULTS: There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C-reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27-1.61). In the sub-group of patients with elevated C-reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003). CONCLUSION: Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab.

Adult↗
PubMed2004

Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease (CD) and/or ulcerative colitis (UC). METHODS: Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients (cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios. RESULTS: The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD (cohort 1: 11% v 5%, odds ratio (OR) 2.31 (95% confidence interval (CI) 1.28-4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 (95% CI 1.24-4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 (95% CI 1.07-3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p = 0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately. CONCLUSION: We have reported on a novel association of the TLR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD.

Adolescent↗
PubMed2004

Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis.

BACKGROUND AND AIMS: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. METHODS: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. RESULTS: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint non-parametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. CONCLUSION: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population.

Chromosomes, Human, Pair 14↗
PubMed2002

Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease.

Both genetic and environmental factors have been implicated in the etiology of inflammatory bowel diseases (IBD) i.e., Crohn's disease (CD) and ulcerative colitis (UC). Polymorphisms in cytokine genes are likely to influence an individual's predisposition to IBD. In intron 2 of the interleukin-1 receptor antagonist (IL-1ra) gene, a variable number of an 86-bp tandem repeat (VNTR) polymorphism leads to the existence of five different alleles. In order to analyze the association between certain IL-1ra VNTR-alleles and IBD, we investigated the IL-1ra genotype and allele frequencies in 342 unrelated IBD patients and in 401 healthy control individuals. CD patients were also genotyped for the three main associated variants in the NOD2/CARD15 gene. In the IBD group, a significant decrease in the frequency of IL-1ra allele 1 (P=0.048) compared to controls was observed. The frequency of IL-1ra genotype 1/1 was significantly lower in the IBD population vs the control group (P=0.018). Analysis of the CD population without NOD2 homozygotes and compound heterozygotes revealed a more significant decrease in IL-1ra genotype 1/1 compared to controls (P=0.038). These results support the hypothesis that the IL-1ra VNTR-polymorphism could be among the genetic factors that are of importance in IBD susceptibility.

Adolescent↗
PubMed2002

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease.

OBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNF have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CD patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease.

Adolescent↗
PubMed2002

A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.

BACKGROUND: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. METHODS: Two-hundred-and-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal disease, and as either complete fistula healing (complete) or a decrease of at least 50% of the number of draining fistulas on two consecutive visits between weeks 0 and 18, for fistulizing disease. CRP and serum TNF-alpha levels were measured at week 0 before treatment and were compared between responders and non-responders. Patients were genotyped for the -308 TNF gene polymorphism, and allelic as well as genotype frequencies were compared between responders and non-responders. RESULTS: There were 73.2% responders (46.4% complete and 26.8% partial) and 26.8% non-responders. Response rates were similar in luminal and fistulizing diseases. CRP level before treatment was significantly higher in responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P = 0.02). Furthermore, response rate was significantly higher in patients with elevated CRP (>5 mg/l) than in patients with a normal CRP value (<5 mg/l) before treatment (76% versus 46%; P=0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphism were not significantly different between responders and non-responders--with the exception of a slightly higher TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. CONCLUSION: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment.

Adolescent↗
PubMed2001

Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease.

The inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) are complex multifactorial traits involving both environmental and genetic factors. Recent studies have shown the important role of pro-inflammatory cytokines and chemokines, including RANTES, in IBD. RANTES is the natural ligand for the CC-chemokine receptor 5 (CCR5). The chromosomal location of the CCR5 gene on 3p21 coincides with an IBD-susceptibility locus identified by genome-wide scanning. A 32-bp deletion (A32) in the CCR5 gene results in a nonfunctional receptor and is found with high frequency in Caucasians. In this study, we investigated the presence of the CCR5delta32 allele in a large cohort of IBD patients and in a healthy control population. Blood samples were obtained from 538 unselected IBD cases (433 unrelated IBD patients: 289 CD, 142 UC, 2 indeterminate colitis; 105 affected first-degree relatives) and 135 unaffected first-degree family members. Of the IBD patients, 36% had familial IBD with at least two members being affected. There were no significant differences in the CCR5delta32 mutation frequency between IBD patients and healthy controls, nor between CD and UC patients. There was no correlation between the CCR5delta32 genotype and the age at IBD-diagnosis, the frequency of surgical intervention, or disease localization. Only the association between CCR5delta32 homozygosity and the presence of anal lesions in CD patients was statistically significant (P=0.007). Analysis by the transmission/disequilibrium test showed no significant transmission distortion to the probands or their clinically silent siblings. Based on these results, it is unlikely that the CCR5delta32 allele is an important marker for predisposition to IBD.

Adolescent↗
PubMed2001

Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease.

The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC), are complex multifactorial traits involving both environmental and genetic factors. Mannan-binding lectin (MBL) plays an important role in non-specific immunity and complement activation. Point mutations in codons 52, 54 and 57 of exon 1 of the MBL gene are associated with decreased MBL plasma concentrations and increased susceptibility to various infectious diseases. If these MBL mutations could lead to susceptibility to putative IBD-etiological microbial agents, or could temper the complement-mediated mucosal damage in IBD, MBL could function as the link between certain microbial, immunological and genetic factors in IBD. In this study, we investigated the presence of the codon 52, 54 and 57 mutations of the MBL gene in 431 unrelated IBD patients, 112 affected and 141 unaffected first-degree relatives, and 308 healthy control individuals. In the group of sporadic IBD patients (n = 340), the frequency of the investigated MBL variants was significantly lower in UC patients when compared with CD patients (P = 0.01) and with controls (P = 0.02). These results suggest that MBL mutations which decrease the formation of functional MBL could protect against the clinical development of sporadic UC, but not of CD. This could be explained by the differential T-helper response in both diseases.

Adolescent↗
PubMed2001

Evidence for inflammatory bowel disease of a susceptibility locus on the X chromosome.

BACKGROUND & AIMS: The technique of genomewide scanning has been applied successfully in inflammatory bowel disease (IBD). A number of putative susceptibility loci have been identified through genomewide searches including replicated regions of linkage on chromosomes 12, 16, 6 (the HLA region), and 14. We have investigated the contribution of the X chromosome in 145 Belgian affected relative pairs. METHODS: In the first stage of the study, 79 (68 CD, 11 mixed) sibling pairs were genotyped at 12 microsatellite markers covering the X chromosome. In the second stage, 10 additional markers in the X-pericentromeric region were studied in the families involved in stage 1 together with 62 additional families (52 sibling pairs, 14 second-degree relative pairs). RESULTS: In the first stage, evidence for linkage was found over a 30-cM pericentromeric region spanning dXs991, dXs990, and dXs8096 (multipoint maximum LOD score in the CD subgroup, 2.5; P = 0.0003). The remainder of the X chromosome was excluded (exclusion under LOD-2) for a locus with lambda(s) = 2. Fine mapping in the second stage confirmed linkage, and narrowed and shifted the linked region to Xq21.3 around dXs1203 (nonparametric linkage [NPL], 2.90; P = 0.0017). The NPL-1 interval around the linkage peak comprises 19.7 cM. CONCLUSIONS: These data provide suggestive evidence for the presence and chromosomal location of an X-linked susceptibility gene in IBD.

Chromosome Mapping↗
PubMed2001

Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in inflammatory bowel disease.

BACKGROUND & AIMS: Anti-Saccharomyces cerevisiae antibody (ASCA) is a serologic marker associated with Crohn's disease (CD). Although there is still discussion on its clinical value, several companies each promote their own ASCA assay to be used in the gastroenterologist's practice at considerable expense. The aim of this study was to determine whether different ASCA assays agree sufficiently well for the results to be used interchangeably. METHODS: Blood obtained from a large cohort of IBD patients with inflammatory bowel disease (IBD; 100 with CD, 100 with ulcerative colitis [UC]) and 178 controls (100 healthy blood donors and 78 patients with non-IBD diarrheal illnesses) was studied with 4 different ASCA assays. Sensitivity, specificity, and positive predictive value were compared. Agreement between assays was evaluated. RESULTS: Sensitivity of ASCA for CD ranged between 41% and 76%. Sensitivity was inversely related to specificity and positive predictive value. Results correlated well overall (range = 0.54-0.90) and the different ROC curves showed good agreement. When recalculated cutoff points were used, interchangeability increased. However, large differences were seen when absolute values were compared. CONCLUSIONS: A large range in sensitivities and specificities of ASCA for CD is seen with different ASCA assays, mainly as a consequence of the cutoff value chosen for each individual assay. Although agreement between and within assays is good, caution is important when absolute values are used. Standardization of ASCA measurements is greatly needed.

Adolescent↗
PubMed2001

Inflammatory bowel disease in spouses and their offspring.

BACKGROUND & AIMS: The rarity of inflammatory bowel disease (IBD) in both husband and wife is often given as an argument against an infectious origin. We registered conjugal instances of IBD in Northern France and in Belgium between 1989 and 2000. METHODS: Couples were assigned to group A if both partners had symptoms of IBD before cohabitation, to group B if one spouse had IBD before cohabitation and the other experienced first symptoms afterwards, and to group C if both partners got the disease after cohabitation. Risk of IBD was assessed in their offspring. RESULTS: Thirty conjugal instances were registered. Seventeen were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed. Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD occurred in the first affected spouse an average of 9 years after cohabitation and in the second spouse an average of 8.5 years later. Group C conjugal forms were more frequent than expected by chance (P < 0.02). Fifty-four children were born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's disease at a median age of 15 years. CONCLUSIONS: The frequency of conjugal forms of IBD suggests an etiologic role for environmental factors. Offspring of 2 affected parents have a high risk of developing IBD.

Adolescent↗
PubMed2001

Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis.

BACKGROUND & AIMS: Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids. METHODS: Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy. RESULTS: Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed. CONCLUSIONS: Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC.

Adult↗
PubMed2001

Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: a study in IBD families.

BACKGROUND: Serologic markers anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies with perinuclear staining (pANCA) have been proposed to study the immunopathogenesis of IBD. Their measurement may allow better phenotyping of the disease and the detection of subclinical disease. AIMS: To test the hypothesis that serological markers identify an immunologic trait related to disease susceptibility. We also wanted to test the hypothesis that ASCA is a marker related to abnormal tissue permeation by common antigens. METHODS: We studied the prevalence of pANCA and ASCA in a large cohort of sporadic and familial inflammatory bowel diseases and their unaffected relatives and spouses. Kinetics of ASCA was studied and the relationship between ASCA and 51Cr-EDTA intestinal permeation was investigated. RESULTS: ASCA was associated with sporadic Crohn's disease (CD) (63%), with Crohn's patients belonging to pure CD families (62%) and also with their unaffected family members (21%). pANCA was associated with UC (58%). The prevalence of ASCA in CD patients belonging to mixed families was strikingly low (33%). ASCA was a stable marker throughout the disease and was not related to an increased small intestinal permeability. CONCLUSION: ASCA is strongly associated with familial CD in Belgium, and 21% of healthy family members also display the marker. The association is much weaker in patients belonging to mixed families. ASCA is a stable marker and is not a secondary phenomenon due to increased intestinal permeability.

Adolescent↗
PubMed2001

Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease.

OBJECTIVES: Correct diagnosis of inflammatory bowel disease (IBD), especially the differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is highly important toward treatment and prognosis. Serological markers are noninvasive diagnostic tools that could be of value in differentiating CD from UC, in cases of indeterminate colitis, and in the identification of subgroups in IBD. The aim of this study was to evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) for IBD. METHODS: ASCA and pANCA were studied in a large cohort of consecutive IBD patients (n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157). An indirect immunofluorescence technique and a standardized ELISA were performed for detection of pANCA and ASCA, respectively. RESULTS: Prevalence of ASCA and pANCA was high in CD patients (59.7%) and UC (49.7%) patients, respectively. Positivity for both markers was significantly lower in healthy and non-IBD controls. Accuracy data (sensitivity, specificity, PPV, and NPV, respectively) for differentiating IBD from controls are as follows: ASCA+: 60% (243/407), 91% (345/378), 88% (243/276), and 68% (345/509); pANCA+: 50% (73/147), 95% (605/638), 69% (73/106), and 89% (605/679); ASCA+/pANCA-: 56% (229/407), 94% (355/378), 91% (229/252), and 67% (355/533); and pANCA+/ASCA-: 44% (65/147), 97% (620/638), 78% (65/83), and 88% (620/702). CONCLUSIONS: Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests. The combination of tests is probably more powerful, although, clinical subgroups still need to be defined. The usefulness of these markers in indeterminate colitis needs to be studied prospectively.

Adolescent↗