Reduced mucosal antimicrobial activity in Crohn's disease of the colon

OBJECTIVES: In order to maintain the mucosal barrier against luminal microorganisms the intestinal epithelial cells synthesise various broad-spectrum antimicrobial peptides including defensins and cathelicidins. Recent studies indicate that both may be deficient in Crohn's disease. To elucidate the possible functional consequences of this deficiency antimicrobial activity in colonic mucosa from patients with inflammatory bowel disease and healthy controls was investigated. METHODS: A flow cytometric assay was established to quantitate bacterial killing and test the antibacterial activity of cationic peptide extracts from colonic biopsies taken from patients with active or inactive ileocolonic or colonic Crohn's disease (n = 22), ulcerative colitis (n = 29) and controls (n = 13) against clinical isolates of Bacteroides vulgatus and Enterococcus faecalis or the reference strains Escherichia coli American Type Culture Collection (ATCC) 25922 and Staphylococcus aureus ATCC 25923. RESULTS: Compared with controls and ulcerative colitis there was a reduced antimicrobial effect in Crohn's disease extracts that was most evident against B. vulgatus. The antimicrobial effect against E. coli and E. faecalis was significantly lower in Crohn's disease compared with ulcerative colitis. Activity against S. aureus disclosed a similar pattern, but was less pronounced. The differences were independent of the inflammation status or concurrent steroid treatment. Bacteria incubated with biopsy extracts from ulcerative colitis patients frequently showed a characteristic change in cell size and granularity, compatible with more extensive membrane disintegration, compared with bacteria incubated with extracts from controls or Crohn's disease. CONCLUSION: Crohn's disease of the colon is characterized by a diminished functional antimicrobial activity that is consistent with the reported low antibacterial peptide expression.     

Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer

BACKGROUND & AIMS: Altered mucosal glycosylation in inflammatory bowel disease and colon cancer could affect mucosal bacterial adherence. This study aimed to quantify and characterize mucosa-associated and intramucosal bacteria, particularly Escherichia coli, in these conditions. METHODS: Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn's disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis. RESULTS: Mucosa-associated and intramucosal bacteria were cultured more commonly in Crohn's disease (79%, P = 0.03; and 71%, P < 0.01, respectively), but not ulcerative colitis (38% and 48%), than in noninflamed controls (42% and 29%) and were commonly cultured from colon cancers (71% and 57%). Mucosa-associated E. coli, which accounted for 53% of isolates, were more common in Crohn's disease (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramucosal E. coli: Crohn's disease, 29%; controls, 9%. E. coli expressed hemagglutinins in 39% of Crohn's cases and 38% of cancers but only 4% of controls, and this correlated (P = 0.01) with adherence to the I407 and HT29 cell lines. Invasion was cell-line dependent. E. coli, including nonadherent isolates, induced interleukin-8 release from the cell lines. E. coli adhesins showed no blood group specificity, excepting 1 cancer isolate (HM44) with specificity for the Thomsen-Friedenreich antigen, but they could be blocked by soluble plantain fiber. CONCLUSIONS: These studies support a central role for mucosally adherent bacteria in the pathogenesis of Crohn's disease and colon cancer. Soluble plant fibers that inhibit their adherence have therapeutic potential.     

Properties of strains of Escherichia coli carried in different phases of ulcerative colitis

Strains of E. coli from the faeces of patients with active ulcerative colitis and with colitis in remission were examined for haemolysin and necrotoxin production. Cultures from 63 patients with active colitis grew haemolytic E. coli in 23 (37%) as compared with 24 (21%) from 115 patients whose disease was in remission (p < 0.05). The corresponding proportions for necrotoxin-producing strains were 22% and 12%. Of 35 patients investigated both in relapse and remission of the colitis, 14 changed their carriage of haemolytic E. coli. Thirteen of these carried haemolytic organisms in relapse but not in remission, and one carried haemolytic organisms in remission but not in relapse (p < 0.01).Strains of E. coli were also examined from specimens of faeces obtained at weekly intervals for 28 weeks from 19 patients. The acquisition of haemolytic or necrotoxic E. coli strains tended to follow rather than precede the onset of the attack in the four patients who developed a relapse of the disease during this period. Among these 19 patients haemolytic and necrotoxic strains were found most commonly when blood was regularly present in the faeces. These facts suggest that conditions in the bowel during a relapse of colitis tend to favour the presence of haemolysin- and necrotoxin-producing organisms, rather than that these organisms cause the relapse.Of 50 strains of E. coli from patients treated with sulphasalazine tested for sensitivity to sulphapyridine 49 were resistant. There was no clear relation between the activity of the colitis and the presence of any of the 27 serotypes of E. coli examined.     

Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography

BACKGROUND: To study the vascularization in the diseased bowel wall by power Doppler sonography in patients with inflammatory bowel disease. PATIENTS AND METHODS: The diseased bowel wall was investigated in 99 patients with inflammatory bowel disease (60 patients with Crohn's disease and 39 patients with ulcerative colitis) either with active disease or in remission by B-mode and power Doppler sonography. Disease activity was determined by clinical indices. Twenty healthy age and sex matched individuals served as controls. RESULTS: Bowel wall was thickened in active Crohn's disease (mean 7 mm, range 4-14) and ulcerative colitis (mean 5 mm, range 2-15) as compared to healthy controls (mean 2 mm, range 1-3), p < 0.001. In contrast to healthy controls blood vessels were detected in the bowel wall in 100 % of patients with active Crohn's disease and 91 % with active ulcerative colitis. Vascularization was significant decreased in patients with quiescent versus active disease in ulcerative colitis (p < 0.05), while in Crohn's disease there was no significance between active and remission phase. CONCLUSIONS: Thickened and hypervascularized bowel wall are characteristic findings in inflammatory bowel disease. A combination of B-mode and power Doppler sonography offers an additional noninvasive procedure for the determination of activity in patients with inflammatory bowel disease.     

Colicinogeny in chronic inflammatory bowel disease

There are several indirect arguments for a possible role of colicins in chronic inflammatory bowel disease (IBD). Colicinogeny was therefore investigated in 54 patients with ulcerative colitis, 39 patients with Crohn's disease, and 160 clinically healthy controls. No significant difference was found among the examined groups. The leukocyte migration inhibition test (with colicins as antigens) was performed to estimate cellular hypersensitivity to colicins. Migration indices not exceeding the normal range in controls contrasted with abnormal values found in 36% of ulcerative colitis and 80% of Crohn's disease patients. The results are believed to be proof of cellular hypersensitivity of IBD patients to colicins of their own Escherichia coli strains. The importance of this finding must be further clarified.     

Influence of inflammatory bowel disease on intestinal microflora.

The microflora of the jejunum, ileum, and colon has been studied from operative samples in Crohn's disease (n = 30), ulcerative colitis (n = 15), and controls (n = 40). There was no significant difference in the flora of patients with ulcerative colitis compared with controls. In Crohn's disease there was a significant increase in E. coli (P less than 0.001) and B. fragilis (P less than 0.001) in the ileum and of E. coli (P less than 0.001) and lactobacilli (P less than 0.01) in the colon. The abnormal ileal flora in Crohn's disease was unrelated to serological evidence of disease activity (indices: ESR, serum albumin, serum seromucoids), diameter of the ileum, or excision of the ileocaecal valve. The abnormal colonic flora in Crohn's disease was not related to presence of macroscopic colitis.     

Agglutinins to bacteria in Crohn's disease.

Sera from patients with Crohn's disease were tested for antibodies against organisms which are thought to cause inflammatory bowel disease in animals, or have been implicated in human Crohn's disease. Control sera were collected from healthy individuals and patients with ulcerative colitis. Sera from Crohn's disease and controls failed to agglutinate Clostridium colinum or Campylobacter sputorum subsp. mucosalis and two strains of Mycobacterium paratuberculosis (M26 and M27). Most of the sera agglutinated a Citrobacter freundii variant, Mycobacterium paratuberculosis (M28) and Mycobacterium avium (M41) but Crohn's disease sera did not differ from controls. A complement fixation test against Chlamydia gave more positive reactions in patients with Crohn's disease and colitis than in healthy controls. There was a clear difference between the sera from patients with Crohn's disease and other sera, including ulcerative colitis, in agglutination tests with the commensal coccoid rods of the genera Eubacterium and Peptostreptococcus; in these tests 54% of sera from Crohn's disease were positive compared with 11% in ulcerative colitis and none of the sera from healthy controls. All the results were essentially negative with the exception of those from Eubacterium and Peptostreptococcus and these bacteria merit investigation.     

Cytokine production in patients with inflammatory bowel disease.

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn's disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn's disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn's disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn's disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn's disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn's disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn's disease, or both.     

Antineutrophil cytoplasmic autoantibodies in inflammatory bowel diseases.

Antineutrophil cytoplasmic autoantibodies have been recently reported in sera from patients with inflammatory bowel disease. We report our experience based on 90 patients with ulcerative colitis, 148 patients with Crohn's disease, and 60 controls. Determination of antineutrophil cytoplasmic autoantibodies was performed by the indirect immunofluorescence technique on ethanol fixed leucocytes. The specificities for proteinase 3, myeloperoxidase, and lactoferrin were tested by enzyme-linked immunosorbent assay. Forty-three out of 90 (48%) patients with ulcerative colitis, 10 out of 148 (7%) patients with Crohn's disease, and none of controls were positive by indirect immunofluorescence technique. All patients but two with positive immunofluorescence exhibited a perinuclear staining pattern. Among patients with ulcerative colitis, there was no relationship between the presence of perinuclear antineutrophil cytoplasmic autoantibodies and disease location or activity. Seven out of 20 (35%) patients with ulcerative colitis who had a previous colectomy (including 1 with ileoanal anastomosis) had perinuclear antineutrophil cytoplasmic autoantibodies. Antineutrophil cytoplasmic autoantibody specificity was not directed against myeloperoxidase, proteinase 3 or lactoferrin in sera from patients with inflammatory bowel diseases. Inflammatory bowel diseases are associated with a new subset of antineutrophil cytoplasmic autoantibodies. Among patients with Crohn's disease and ulcerative colitis, the sensitivity and specificity of the presence of perinuclear antineutrophil cytoplasmic autoantibodies for ulcerative colitis was 46% and 93%, respectively. Their presence reinforces the likelihood of underlying immunologic dysregulation in ulcerative colitis. Identification of the autoantigen(s) to which these antibodies are directed might facilitate the understanding of inflammatory bowel disease pathophysiology.     

Pulmonary function tests, high-resolution computed tomography findings and inflammatory bowel disease

AIM: The association between inflammatory bowel disease and pulmonary involvement has not been clearly established. The aim of this prospective study was to define the features of pulmonary function tests and high resolution computed tomography in inflammatory bowel disease patients and the relation between these and disease activity. METHOD: Fifty-two patients with inflammatory bowel disease (20 with Crohn's disease and 32 with ulcerative colitis) were enrolled. The standard pulmonary function tests and thorax high resolution computed tomography findings were investigated with respect to inflammatory bowel disease activity. Crohn's disease activity index and the Rachmilewitz endoscopic activity index for ulcerative colitis were used to assess disease activity. Medications used and smoking status were also documented. RESULTS: Among the patients with ulcerative colitis, 6.25% had an obstructive and/or restrictive ventilatory defect compared with 25% of the patients with Crohn's disease. Fifty percent of the patients with ulcerative colitis and 60% of the patients with Crohn's disease showed abnormal findings in high resolution computed tomography. Pulmonary function tests and high resolution computed tomography abnormalities did not differ significantly between Crohn's disease and ulcerative colitis. No significant difference related to inflammatory bowel disease activity was found (P > 0.05). CONCLUSION: Findings of high resolution computed tomography and the pulmonary function tests did not differ between ulcerative colitis and Crohn's disease. Bowel disease activity did not seem to affect these measurements.     

Loss of interleukin-2-producing intestinal CD4+ T cells in inflammatory bowel disease.

Interleukin-2 activity of intestinal lamina propria mononuclear cells is decreased in Crohn's disease and ulcerative colitis patients compared with control patients with noninflammatory bowel disease. Factors that might be responsible for this phenomenon were investigated. Most interleukin-2 activity was produced by helper (CD4+) T cells. These were present in comparable numbers in both inflammatory bowel disease and control cultures, but the frequency of interleukin-2-producing cells was significantly (3-4 times) lower among Crohn's disease and ulcerative colitis than control cells. In agreement with this finding, levels of interleukin-2 messenger RNA were substantially decreased in both forms of inflammatory bowel disease compared with controls. Mucosal CD8+ T cells and plastic-adherent cells were unable to suppress interleukin-2 activity by autologous or allogeneic CD4+ T cells. The rate of interleukin-2 absorption was similar for inflammatory bowel disease and control cells. Induction of interleukin-2 by different stimuli (phorbol ester, phytohemagglutinin, or anti-CD3 monoclonal antibody) before or after incubation under basal conditions ("resting") failed to normalize the capacity to generate interleukin-2 by Crohn's disease and ulcerative colitis cells. Prostanoids (prostaglandin E2 and 6-keto-prostaglandin F1 alpha) were produced in large amounts in cultures of inflammatory bowel disease cells, but inhibition by indomethacin failed to restore interleukin-2 activity to control levels. Finally, supernatants from Crohn's disease and ulcerative colitis cell cultures failed to suppress interleukin-2 production by control CD4+ T cells. Our results show that the low interleukin-2 activity detected in inflammatory bowel disease mucosa is not caused by activated suppressor cells, excessive lymphokine utilization or immune stimulation, a defective response to activation signals, or production of inhibitory substances. Rather, the low interleukin-2 activity appears to be related to a loss of interleukin-2-producing mucosal CD4+ T cells. It is concluded that abnormalities of intestinal CD4+ T-cell function are associated with the immunopathogenesis of Crohn's disease and ulcerative colitis.     

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.     

Bacterial L-form isolation from inflammatory bowel disease patients

This study was designed to investigate a possible relationship between bacterial L forms and inflammatory bowel disease. Homogenates of intestinal mucosal biopsies from Crohn's disease, ulcerative colitis, and control patients underwent bacterial culture on hypertonic media designed for the recovery of L-form bacteria and parental organisms. L forms were recovered from 24 of 71 Crohn's disease, 51 of 121 ulcerative colitis, and 2 of 140 control biopsy specimens. These isolation rates are significantly different when Crohn's disease biopsy specimens (p less than 0.001) and ulcerative colitis biopsy specimens (p less than 0.001) are compared with controls. Six different L-form types were recovered, of which the most common were Escherichia coli and Streptococcus fecalis. No marked differences were observed in L-form recovery rates or L-form types recovered between Crohn's disease and ulcerative colitis patients. Drug treatment of inflammatory bowel disease patients did not affect L-form recovery rates or the type of L forms recovered. The results suggest either that L forms are involved in the causation of inflammatory bowel disease or that their presence in mucosal biopsy tissues is a result of the disease process.     

Mycobacteria and inflammatory bowel disease. Results of culture

We have been able to isolate mycobacteria from intestinal specimens obtained by surgical resection or endoscopic biopsy from patients with Crohn's disease, ulcerative colitis, and noninflammatory bowel diseases. Nineteen slow-growing (Runyon groups I and III) and 17 rapid-growing (Runyon group IV) mycobacterial isolates were obtained. Slow-growing mycobacteria were recovered from approximately one-third of intestinal biopsy specimens from Crohn's disease, one-quarter of ulcerative colitis biopsies, and 40% of biopsies from noninflammatory bowel disease patients. Isolates were most commonly members of the Mycobacterium avium-complex. One isolate (from an ulcerative colitis patient) was biochemically similar to the Mycobacterium strain previously associated with Crohn's disease, and one from a Crohn's disease patient was Mycobacterium kansasii. The rapid-growing organisms were members of the Mycobacterium fortuitum-complex. In addition to conventional mycobacteria, spheroplasts (cell wall-defective forms) were isolated from 12 patients with Crohn's disease (most often from surgically resected colon) and 3 patients with ulcerative colitis; none were isolated from non-inflammatory bowel disease patients. We have been unable to identify a consistent relationship between the presence, or the species, of Mycobacterium and Crohn's disease. Our results do not support the proposed role of a specific mycobacterium in the pathogenesis of Crohn's disease. The cause of Crohn's disease remains unclear.     

Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis.

The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2 enzymatic activity were measured for colonic mucosal biopsy samples obtained from patients with either Crohn's disease of the colon or ulcerative colitis, and control patients without inflammatory bowel disease. Immunoreactive group II PLA2 (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of Crohn's disease patients were significantly higher than those in inactively inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls. IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative colitis patients were significantly higher than those in the colonic mucosa of the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These results suggest that an increase in PLA2 enzymatic activity in inflamed colonic mucosa of Crohn's disease and ulcerative colitis was mainly attributed to increased protein content of group II PLA2, and that an increase in mucosal group II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's disease and ulcerative colitis.     

Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls. RESULTS: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01). CONCLUSION: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.     

Serum antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease are mainly associated with ulcerative colitis. A correlation study between perinuclear antineutrophil cytoplasmic autoantibodies and clinical parameters, medical, and surgical treatment.

Perinuclear antineutrophil cytoplasmic antibodies have recently been demonstrated in the sera of patients with inflammatory bowel disease. Three hundred and sixty six sera obtained from 120 patients with ulcerative colitis, 105 patients suffering from Crohn's disease and 49 non-inflammatory bowel disease controls were tested in two laboratories, using an indirect immunofluorescence assay. In addition, a fixed-neutrophil enzyme linked immunoadsorbent assay (ELISA) was evaluated in one of the two laboratories. The results in the immunofluorescence test showed a high degree of correlation between the two laboratories (Kappa coefficient = 0.8). Ninety five of the 120 (79%) ulcerative colitis patients had a positive test whereas only 14 of the 105 (13%) patients with Crohn's disease were positive. Sera from four patients suffering from primary sclerosing cholangitis were positive as well as four of the 45 control sera (9%). The sensitivity of the perinuclear antineutrophil cytoplasmic antibody immunofluorescence test for the diagnosis of ulcerative colitis was 0.75 with a specificity of 0.88 and a positive predictive value of 0.88 (all sera). In the ELISA technique 37 of 94 ulcerative colitis sera and one of the 68 Crohn's disease sera were positive. In the control group only one of the patients suffering from primary sclerosing cholangitis reacted positively (32 non-inflammatory bowel disease sera tested). The ELISA technique had a high specificity (0.97), but a low sensitivity (0.39). There was no relation of perinuclear antineutrophil cytoplasmic antibodies in ulcerative colitis patients or in Crohn's disease patients with disease activity, duration of illness, localisation, extent of disease, previous bowel operations or medical treatment. The clinical significance of perinuclear antineutrophil cytoplasmic antibody positive and negative subsets in both groups of patients thus remains unexplained. Our study confirms that determination of serum antineutrophil cytoplasmatic antibodies in patients with inflammatory bowel disease may differentiate ulcerative colitis from Crohn's disease. Further immunological studies are needed to explain the absence of these antibodies in a subset of ulcerative colitis patients and their role in the pathogenesis of the disease.     

Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?

OBJECTIVE: Lipoprotein (a) is recognized as a risk factor for arterial and venous thrombosis, a property that might be related to its structural similarity to plasminogen. Since patients with inflammatory bowel disease frequently suffer from thromboembolic events, we studied the role of lipoprotein (a) in conjunction with lipids and apolipoproteins in Greek patients with ulcerative colitis and Crohn's disease. METHODS: Lipoprotein (a), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1 and apolipoprotein B-100 were determined in sera from 129 consecutive fasting Greek patients with inflammatory bowel disease (66 with ulcerative colitis and 63 with Crohn's disease) and from 66 matched healthy controls. RESULTS: In Crohn's disease patients, the mean serum lipoprotein (a) level was significantly higher than in control patients (41.2 mg/dl vs 22.9 mg/dl; P = 0.005). Mean apolipoprotein A-1 and apolipoprotein B-100 levels were significantly lower in Crohn's disease patients than in the controls. In ulcerative colitis patients the mean levels of lipoprotein (a) and apolipoprotein A-1 were not significantly different to the controls, but the levels of apolipoprotein B-100 were significantly lower. Raised levels of lipoprotein (a) of > 30 mg/dl were found in 29 Crohn's disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohn's disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. CONCLUSIONS: Our results suggest that Crohn's disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohn's disease patients may possibly expose them to a higher risk of thrombosis.     

Serum gastrin levels in patients with inflammatory bowel disease

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.     

Anergy to dinitrochlorobenzene and depression of T-lymphocytes in Crohn's disease and ulcerative colitis.

Skin reactivity to dinitrochlorobenzene (DNCB) and levels of circulating T-lymphocytes were measured in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 12 normal control subjects. Diminished reactivity to DNCB was demonstrated in 87% of patients with Crohn's disease (P less than 0-001) and in 53% with ulcerative colitis (P less than 0-02), as compared with only 8-5% of controls; anergy was more frequent in Crohn's disease than in ulcerative colitis (P less than 0-05). Levels of circulating T-lymphoctes were also depressed in both Crohn's disease and ulcerative colitis (P less than 0-001) as compared with controls, with the values lower in Crohn's disease than in ulcerative colitis (P less than 0-02). There were no correlations of DNCB response with extent, duration, or severity of disease nor with T-cell levels within any patient group. These data provide further support for the concept that there is impairment of cell-mediated immunity among many patients with chronic inflammatory bowel disease, including both Crohn's disease and ulcerative colitis.