Seroreactivity to microbial components in Crohnʼs disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients
Mária PappI AltorjayGary L. NormanZakera ShumsKároly PalatkaZsuzsanna VitálisIldikó FöldiGabriella LakosJudit TumpekM. UdvardyJolán HársfalviSimon FischerPéter L. LakatosÁgota KovácsLászló BeneTamás MolnárZsolt TulassayPál MihellerGábor VeresJ. PappPéter L. Lakatos
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Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients.In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts.Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC.Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.Keywords:
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ASCA는 크론병에, 그리고 pANCA는 궤양성대장염에 비교적 특이한 자가항체로 알려져 있으나 아직 논란이 있는 실정이다. 본 연구에서는 크론병, 궤양성 대장염, 베체트 장염 그리고 장결핵환자와, 그 가족들을 대상으로 ASCA와 pANCA를 측정하여 진단적 유용성에 대하여 평가하고자 하였다. 1999년 1월부터 2000년 12월까지 서울대학교병원에서 치료를 받고 있는 크론병 85명, 궤양성 대장염 77명, 베체트 장염 36명, 장결핵
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Introduction. The currently known prognostic criteria for biological therapy have limitations and have not been widely used in clinical practice. Aim. Find predictors of the effectiveness of biological therapy with infliximab in patients with ulcerative colitis. Materials and methods. The object of the study was patients (n = 52) diagnosed with Ulcerative Colitis in the active form of the disease, including 27 men and 25 women undergoing therapy with infliximab. Follow-up was carried out for three years from the start of therapy. The age of the examined persons ranged from 19 to 64 years (mean age 34.76 ± 2.13 years). The mean score on the Mayo scale was 6.1 ± 3.49. Results. In the course of our study, we obtained the following data on the effectiveness of infliximab therapy in patients with severe ulcerative colitis: a significant improvement in the dynamics of laboratory and instrumental parameters was recorded in 25 people (43.8%); the onset of stable clinical remission — in 15 people (26.3%); disease progression — in 5 cases (8.7%); lack of dynamics or a less pronounced effect — in 12 cases (21.2%). Conclusions. We have identified a system of clinical and laboratory factors that make it possible to predict the effectiveness of biological therapy with infliximab in patients with ulcerative colitis. The mathematical model in the form of a discriminant function makes it possible to divide patients into groups depending on the possible effect of the use of biological therapy with infliximab before its initiation (the sensitivity of the model is 83.3%, the specificity is 71.4%).
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Rescue therapy
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The measurement of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) has recently been suggested as a valuable and noninvasive diagnostic approach in the differentiation of ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). The aim of the study was to determine the prevalence of pANCA and ASCA in patients with inflammatory bowel disease (IBD) subgroups of different clinical course and to assess their accuracy in differential diagnosis.The study was performed in 109 patients: 50 patients with UC, 17 with CD, 18 with IC and 24 non-IBD controls. Antibodies status has been measured with ELISA, using commercial antibody panel by MedTek kits, confirmed by IIF technique using Euroimmun panels.Sensitivity and specificity of pANCA+/ ASCA- pattern for UC diagnosis was 36% and 98%; pANCA-/ASCA+ for CD: 35% and 88%, pANCA/ASCA- for IC: 72% and 63%, respectively. In addition the significant positive correlation between antibodies profiles: pANCA+/ASCA- and active disease; pANCA-/ASCA+ and number of operations, as well as the negative correlation between pANCA-/ASCA- and patient's age has been found.Our study lends further support to the opinions that serologic assessment identifies a large subset of different subtypes of IBD patients.
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Inflammatory Bowel Diseases
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Objective To determine the prevalence of perinuelear antineutrophil cytoplasmic antibodies(pANCA)and anti-Saccharomyces eerevisiae antibodies(ASCA)in Chinese patients with inflammatory bowel disease(IBD),and to evaluate their diagnostic value in ulcerative colitis(UC)and Crohn's disease(CD).Methods One hundred and fifty-six well-characterized,unrelated,consecutive Chinese patients with IBD(126 with UC,30 with CD),and 60 healthy controls were included.Sera were assayed for pANCA and ASCA by the standardized indirect immunofluoreseenee technique.Results The prevalence of pANCA was 42.9% in UC patients and 46.7% in CD patients respectively,which was significantly higher than in healthy controls(5.0%).Sensitivity,specificity,positive and negative predictive value of the pANCA test were 43%,87%,93%,and 27%,respectively for UC.The combination of positive pANCA and negative ASCA was more accurate than the pANCA alone.Positive pANCA was associated with phenotype of severe UC and surgical procedures.ASCA test yielded sensitivity,specificity,positive and negative predictive value of 47%,95%,82%,and 78%,respectively for CD.The combination of negative pANCA and positive ASCA did not change these values significantly.Conclusion pANCA and ASCA were beneficial to the diagnosis of UC or CD diagnosis,and could be used to evaluate the clinical features of the diseases.
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Inflammatory bowel disease; Ulcerative colitis; Serology; Antibody
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Primary Sclerosing Cholangitis
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Several genetic and subclinical markers have been associated with ulcerative colitis.To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies.HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence.Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones.We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.
Subclinical infection
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HLA-DR
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Objective To study the sensibility and specificity of detection of perinuclear anti-neutrophil cytoplasmic antibodies(pANCA) in diagnosis of ulcerative colitis(UC).Methods Serum samples were obtained from 51 patients with ulcerative colitis(UC),15 patiens with Crohn's disease(CD) and 30 patients without intestinal disease as control.pANCA was detected by indirect immunofluorescence assay.Results The sensibility and specificity of p-ANCA in UC patients were 67.75% and 95.56% respectively,but the positive of pANCA in CD patients was 13.33%(2/15).No patients was positive in control group(P0.05).Conclusion Serum pANCA in patients with UC shows a moderately sensibility and a high specificity,it is useful for the diagnosis of UC and differentiation between UC and CD.
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Immunofluorescence
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