ABSTRACT
The allelic frequencies of TaqI, PstI, and variable number of tandem repeat (VNTR) polymorphisms of the IL-1beta, IL-1 receptor (IL-1Re), and IL-1 receptor antagonist (IL-1Ra) respectively, were investigated in black and white patients with inflammatory bowel diseases (IBD) and compared with control individuals. Plasma concentrations of IL-1beta and IL-1Ra were also determined in these individuals. The IL-1beta TaqI(-) allele was significantly more frequent in 50 white IBD patients (60%) compared with 47 white controls (17%), and 20 black patients (20%) (P=0.00001 and P=0.0001, respectively). The IL-1Re PstI(-) allele was significantly more frequent in 20 black patients (75%) compared with 50 white patients (44%) (P=0.0001). The frequency of the IL-1Ra 240-bp allele was lower in black (12%) compared with white controls (25%), (P=0.0151), and the 410-bp allele was more frequent in black (87%) compared with white (73%) controls (P=0.0096). Linkage disequilibrium was found in black individuals homozygous for the 410-bp allele of IL-1Ra, and the PstI(-) allele of IL-1Re (84%) (P=0.0032). There was a significantly increased level of IL-1Ra in black patients compared with white patients and black controls (P=0.0006 and P=0.0008, respectively). The population differences in allelic frequencies of the IL-1 gene cluster and IL-1Ra concentrations suggest that genetic and environmental factors play an important role in susceptibility to IBD.
Subject(s)
Alleles , Ethnicity/genetics , Inflammatory Bowel Diseases/genetics , Interleukin-1/genetics , Multigene Family/genetics , Receptors, Interleukin-1/genetics , Adolescent , Adult , Black or African American , Black People , Case-Control Studies , Deoxyribonucleases, Type II Site-Specific , Female , Gene Frequency/genetics , Homozygote , Humans , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/epidemiology , Interleukin-1/blood , Introns/genetics , Linkage Disequilibrium/genetics , Male , Middle Aged , Minisatellite Repeats/genetics , Polymorphism, Restriction Fragment Length , Receptors, Interleukin-1/blood , South Africa/epidemiology , White People , alpha 1-Antitrypsin/analysisSubject(s)
Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/immunology , Therapeutic Irrigation/methods , Alanine Transaminase/metabolism , Albumins/metabolism , Body Fluids/immunology , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/etiology , Colitis, Ulcerative/immunology , Crohn Disease/diagnosis , Crohn Disease/etiology , Crohn Disease/immunology , Evaluation Studies as Topic , Humans , Immunity, Mucosal , Immunoglobulin G/metabolism , Inflammatory Bowel Diseases/etiology , Intestinal Mucosa/immunology , Prospective Studies , Proteins/metabolismABSTRACT
Management strategies in Crohn's disease and ulcerative colitis should be based on up-to-date information on disease distribution, extent, activity and complications. A system of structured analysis is suggested, with separate consideration of destructive ulceration, inflammatory activity and other factors. Direct investigation of gut immunity by using whole gut lavage fluid (WGLF) is a valuable new technique of clinical investigation in IBD and related disorders. Recent studies have shown that the concentrations of plasma-derived proteins in WGLF provide objective measures of disease activity; and that this activity is a separate phenomenon from destructive ulceration and fibrosis. Neutrophils in the lumen can be in- investigated by cytology, or by assay of neutrophil elastase in WGLF. Cytokines and other immuno-regulatory mediators can also be detected. These new techniques can provide a description of intestinal immunity and inflammation, based on a non-invasive test of 2-4 h duration. Work in progress shows that patients who respond clinically to elemental diet treatment have unusually high concentrations of soluble IL2 receptor in WGLF; cytokine profiles may facilitate the selection of patients suitable for other new treatment modalities.
Subject(s)
Inflammatory Bowel Diseases/diagnosis , Child , Cytokines/metabolism , Female , Gastrointestinal Hemorrhage/etiology , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/immunology , Intestines/immunology , Intestines/pathology , Leukocyte Elastase/metabolism , Male , Neutrophils/enzymology , Pancreatic Elastase/metabolism , Protein-Losing Enteropathies/etiology , Therapeutic IrrigationABSTRACT
BACKGROUND: Fluid obtained by whole gut lavage normally contains traces of immunoglobulin (Ig) G, albumin, and alpha-1-antitrypsin; higher concentrations have been found in patients with inflammatory bowel disease (IBD). METHODS: In a prospective study, 53 lavages were performed in 45 IBD patients (27 Crohn's disease, 18 ulcerative colitis), in whom disease activity was simultaneously assessed by Crohn's Disease Activity Index or Powell Tuck index. Concentration of IgG in lavage fluid was measured by enzyme-linked immunosorbent assay, and of albumin and alpha-1-antitrypsin by immunoturbidimetry. RESULTS: For IgG, concentrations in lavage fluid correlated closely with activity indices: in Crohn's disease, r = 0.723 (P < 0.0001), in ulcerative colitis, r = 0.714 (P < 0.0001). Results for albumin and alpha-1-antitrypsin concentrations were similar to those for IgG, but they were less sensitive in detecting active disease. However, this method cannot be used as a diagnostic test for IBD; normal results were obtained for IgG in 6 (all inactive) of 42 lavages in patients who had unequivocal radiological or endoscopic abnormalities. CONCLUSIONS: Assay of protein concentrations in gut lavage fluid is a simple, objective means of grading disease activity in patients with IBD; its potential uses are likely to be in the evaluation of complex cases and in clinical trials.
