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PubMed1979

In vitro testing of immunoresponsiveness in patients with inflammatory bowel disease: prevalence and relationship to disease activity immunoresponsiveness in IBD.

Abnormalities in the numbers and function of thymus and function of thymus-derived and bone marrow-derived lymphocytes (T and B cells) and K cells were determined in sixty-nine consecutive patients with Crohn's disease or ulcerative colitis. Rosetting techniques to identify subpopulations of lymphocytes showed a significant decrease in E-rosettes (T cells) and significant increase in EA- and EAC-rosettes (B cells) in patients with inflammatory bowel disease when compared to normals. In vitro lymphocyte transformation responses to mitogens and antigens were depressed to a variable degree. Mean levels of K cell activity were not significantly different from normal controls. A considerable degree of individual variation was noted in all groups. When the results of each groups were considered, none of the laboratory variables correlated with the site, duration or activity of disease, therapy, presence of iron deficiency anemia, weight loss or hypoalbuminaemia. Thus, in vitro evidence of abnormal immune responses in patients with inflammatory bowel disease cannot be directly related to clinical or laboratory variables and probably reflects a multi-factorial aetiology.

Adolescent↗
PubMed1995

Usual therapy improves perianal Crohn's disease as measured by a new disease activity index. McMaster IBD Study Group.

Troublesome perianal disease occurs in approximately 35% of patients with Crohn's disease, yet conventional disease activity indices do not reflect the severity of this feature. To assess the degree of impairment and response to therapy, we identified five simple elements and graded each on a 5-point Likert scale in 37 patients at 124 visits. At each visit a Crohn's Disease (CDAI) or Simple Activity Index (HBDAI), Perianal Disease Activity Index (PDAI), and treatment were recorded. The PDAI was validated against physician (MDGA) and patient (PGA) global assessments, and treatment was prescribed for the perianal disease. Measurement error was evaluated in 19 patients who were clinically stable at two consecutive visits. The ability of the PDAI to detect important clinical change was tested in 20 subjects exhibiting a change on PGA at consecutive visits. There were strong correlations between PDAI, MDGA, and PGA scores at all visits (R = 0.66-0.72; p < 0.001), whereas the CDAI and HBDAI correlated poorly with PDAI (R < 0.23). Physicians prescribed more aggressive therapy for higher PDAI scores (r = 0.53). Mean PDAI scores between visits in clinically stable subjects were not significantly different [5.58 +/- 2.79 (initial); 5.42 +/- 2.55 (follow-up); p = 0.63]. PDAI significantly improved between visits when the perianal disease had improved (PDAI score difference 3.05 +/- 2.96; P = .0002). We conclude that the PDAI is simple and clinically useful for patient management. It should now be assessed in a clinical trial.

Adolescent↗
PubMed1996

Evidence of genetic heterogeneity in IBD: 1. The interleukin-1 receptor antagonist in the predisposition to suffer from ulcerative colitis.

OBJECTIVE: To investigate a polymorphism within intron 2 of the interleukin-1 receptor antagonist (IL-1ra) gene in a Dutch white population of patients with ulcerative colitis and Crohn's disease. DESIGN: Genotype and allele frequencies of the polymorphic region in the IL-1ra gene were determined in 111 unrelated patients with ulcerative colitis, 92 patients with Crohn's disease, and 86 healthy controls. METHODS: The polymorphic region on the IL-1ra gene was amplified by the polymerase chain reaction (PCR). The resultant products were analyzed by electrophoresis on 2% agarose gels and stained with ethidium bromide. Amplification of the second exon of HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes was performed by PCR, and Dot-blot analysis with biotin-labelled sequence-specific oligonucleotide probes was used for HLA typing. The standard perinuclear antineutrophil cytoplasmic antibodies (pANCA) indirect immunofluorescence assay was performed according to the protocol described by the First International Workshop on ANCA. RESULTS: The frequency of allele 2 of the IL-1ra gene in ulcerative colitis (27.0%) and Crohn's disease patients (25.5%) did not differ significantly from healthy controls (23.8%). However, the estimate of the relative risk for carriers of allele 2 for ulcerative colitis [odds ratio (OR): 1.35, 95%-confidence interval (CI) from 0.73 to 2.49] was in agreement with a previous British study. The exact test for homogeneity of odds ratios provided no evidence for heterogeneity between both populations (P = 0.35) and therefore confirmed the genetic associated between ulcerative colitis and the IL-1ra allele 2 in a different population. Our data confirm that, in ulcerative colitis, the presence of this allele is a genetic marker for severity of the disease. A significant association was demonstrated between the carriership of allele 2 of the IL-1ra gene and the trend over the three localizations in ulcerative colitis (P = 0.023). The same approach for Crohn's disease when compared with healthy controls did not provide evidence for a similar association. The meta-analysis, based on the British data and our data, yielded: OR = 1.06, 95%-CI from 0.71 to 1.59, and P = 0.767. No association between IL-1ra gene polymorphism, and pANCA and the HLA-DR2 allele was found in ulcerative colitis.

Alleles↗