OBJECTIVES: Immunologic studies have characterized the numbers and types of inflammatory cells in diseased inflammatory bowel disease (IBD) mucosa but have yielded conflicting results regarding intestinal lymphocytes activation in IBD. We investigated the levels of lymphocytes subsets, interleukin-2 receptor, transferrin receptor, and T cell receptors in mainly isolated lamina propria lymphocytes. Including intraepithelial lymphocytes of normal colonic mucosa or IBD (ulcerative colitis and Crohn's disease) mucosa to understand the pathogenesis of IBD. We have results from this study. RESULTS: 1) In comparing ulcerative colitis with control, IL-2R (p < 0.05), TR (p < 0.01), and CD3/HLA-DR (<0.05) showed a significant increase. 2) In comparing Crohn's disease with control, CD3 (P < 0.05), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. 3) In comparing Crohn's disease with ulcerative colitis, CD19 (p < 0.01), TR (p < 0.01), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. CONCLUSION: From these results, there are increased T cell markers, IL-2R, TR, and CD3/HLA-DR in UC, but differently, decreased CD3, TCR alpha/beta and TCR gamma/delta in CD compared with control. In addition, definitive differences in lymphocytes markers, CD19, TR, TCR alpha/beta and TCR gamma/delta, which are higher in UC than in CD, may elucidate the different immunopathogenesis between UC and CD.
Adult ; Antigens, CD3/analysis ; Colitis, Ulcerative/pathology ; Colitis, Ulcerative/immunology ; Colitis, Ulcerative/diagnosis* ; Comparative Study ; Crohn Disease/pathology ; Crohn Disease/immunology ; Crohn Disease/diagnosis* ; Diagnosis, Differential ; Female ; HLA-DR Antigens/analysis ; Human ; Immunophenotyping* ; Intestinal Mucosa/pathology ; Intestinal Mucosa/immunology* ; Male ; Middle Age ; Receptors, Antigen, T-Cell/analysis ; Receptors, Interleukin-2/analysis ; Receptors, Transferrin/analysis ; Sensitivity and Specificity ; Tissue Culture

OBJECTIVE: To investigate the distribution of pulmonary surfactant protein A (SP-A) like molecules and the bridge of frontier host defense and adaptive immune response cell of CD68 positive macrophages in inflammatory bowel disease (IBD). METHODS: Surgical specimens derived from involved areas and normal area of the colon with Crohn disease (CD) and ulcerative colitis (UC) were obtained from Department of Pathology, Rhode Island Hospital, Brown University Medical Center. The distribution of SP-A like molecule in intestine of IBD was detected by immunohistochemistry. RESULTS: SP-A like molecule located in epithelia of intestine, the surface of intestine villi, blood vessels of connective tissue, and some inflammatory cells. The number of macrophages with both SP-A like molecule and CD68 positive was dramatically increased in the inflammatory area than the normal area. Some CD68 positive macrophages expressed SP-A like immunoreactivity by immunofluorescence double labeling. CONCLUSION SP-A is an important host defense molecule in lung, and SP-A expression in large intestine may reflect a close relation between 2 organs in immune response towards inflammation.
Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Colitis, Ulcerative ; immunology ; metabolism ; Colon ; metabolism ; Crohn Disease ; immunology ; metabolism ; Humans ; Immunohistochemistry ; Inflammatory Bowel Diseases ; immunology ; metabolism ; Macrophages ; immunology ; metabolism ; Pulmonary Surfactant-Associated Proteins ; genetics ; metabolism

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9+/-32.5 microg/mL vs 219.8+/-59.0 microg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.
Adolescent ; Antibody Formation/*drug effects ; B-Lymphocytes/metabolism ; Child ; Child, Preschool ; Colitis, Ulcerative/complications/*immunology ; Crohn Disease/complications/*immunology ; Female ; Humans ; Immunoglobulin G/metabolism ; Inflammatory Bowel Diseases/complications/*immunology ; Male ; Pneumococcal Vaccines/*pharmacology ; Polysaccharides/*pharmacology ; Treatment Outcome

OBJECTIVETo evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN).

METHODS32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed.

RESULTSIgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13).

CONCLUSIONSPerioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.

Adult ; Aged ; Body Weight ; Crohn Disease ; immunology ; surgery ; therapy ; Female ; Humans ; Immunoglobulins ; blood ; Male ; Malnutrition ; etiology ; Middle Aged ; Nutritional Status ; Parenteral Nutrition ; Pneumonia ; etiology ; Postoperative Complications ; etiology

BACKGROUND/AIMS: Combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces cereviseae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach to inflammatory bowel disease (IBD) in the pediatric age group. The aim of this study was to test the accuracy of the assay using pANCA and ASCA in diagnosing pediatric ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Sera were collected from 25 patients with IBD (17 with CD, 8 with UC) and 32 healthy controls. The levels of pANCA and ASCA were determined by using a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and an ELISA assay, respectively. RESULTS: In patients with UC, the sensitivity, specificity, and positive predictive value of the pANCA test were 38%, 88%, and 60%, respectively. Such values were not changed significantly in the case of positive pANCA and negative ASCA. The sensitivity, specificity, and positive predictive value of ASCA test in diagnosing CD were 71%, 88%, and 92%, respectively. The combination of pANCA negative and ASCA positive was not significant. CONCLUSIONS: ASCA and pANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions.
Adolescent ; Antibodies, Antineutrophil Cytoplasmic/*analysis ; Antibodies, Fungal/*analysis ; Child ; Child, Preschool ; Colitis, Ulcerative/*diagnosis ; Crohn Disease/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorescent Antibody Technique ; Humans ; Male ; Mannans/immunology ; Predictive Value of Tests ; Saccharomyces cerevisiae/*immunology ; Sensitivity and Specificity

BACKGROUND/AIMS: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human beta-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn's disease (CD) during infliximab therapy. METHODS: We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals. RESULTS: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008). CONCLUSIONS: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.
Adolescent ; Case-Control Studies ; Colon/immunology ; Crohn Disease/*drug therapy/immunology/*metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Gastrointestinal Agents/*therapeutic use ; Humans ; Infliximab/*therapeutic use ; Intestinal Mucosa/immunology ; Leukocytes, Mononuclear/*metabolism ; Male ; Membrane Proteins/*metabolism ; T-Lymphocytes, Regulatory/immunology ; beta-Defensins/*metabolism

OBJECTIVETo search for differentially expressed proteins in the serum of patients with Crohn's disease.

METHODSSerum protein samples obtained from 4 patients with Crohn's disease and 4 normal adults were cross-labeled with different CyDyes and underwent two-dimensional differential in-gel electrophoresis (2-D DIGE) and imaging analysis. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to identify the differentially expressed proteins.

RESULTS2-D DIGE revealed that the protein on spot 973 was overexpressed by 2.55 folds in the serum of patients with Crohn's disease compared with that in normal adults (P<0.05). The protein was identified as CD45 using mass spectrometry.

CONCLUSIONCD45 overexpression in the serum of patients with Crohn's disease may play a role in the disequilibrium of the immune system.

Amino Acid Sequence ; Case-Control Studies ; Crohn Disease ; blood ; immunology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Leukocyte Common Antigens ; blood ; Male ; Molecular Sequence Data ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Thanks to the introduction of immumomodulators and biologics, therapeutic approaches in Crohn's disease have changed significantly during the past decade. Although new biologic therapy has dramatically improved the treatment of Crohn's disease, a substantial number of patients are refractory to these therapies or lose their initial response. Methotrexate (MTX) is a structural analogue of folic acid that can competitively inhibit the binding of dihydrofolic acid to the enzyme dihydrofolate reductase and has been widely used as immunomodulator in rheumatology area for patients with rheumatoid arthritis and psoriasis. Although MTX has also been shown to be an effective agent for remission induction and maintenance of remission in Crohn's disease, the use of MTX in Crohn's disease has not yet been reported in Korea. Herein, we report a case of Crohn's disease patient who was successfully treated with MTX after treatment failure with thiopurine and anti-tumor necrosis factor.
Adult ; Antibodies, Monoclonal/therapeutic use ; Colonoscopy ; Crohn Disease/diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/*therapeutic use ; Infliximab/therapeutic use ; Male ; Methotrexate/*therapeutic use ; Remission Induction ; Tomography, X-Ray Computed ; Tumor Necrosis Factor-alpha/immunology

Intestinal Behcet's disease (BD) refers to colonic ulcerative lesions documented by objective measures in patients with BD. Although the causes of intestinal BD are unknown, genetic, environmental, and immunological factors have been suggested. Intestinal BD is common in BD patients from Far East, while it is uncommon in those from the Middle East. The reasons for such peculiar geographic distribution in intestinal BD are unknown, but may provide clues for the elucidation of putative etiological agents or genetic factors that might be associated with intestinal BD. Although the treatment of Crohn's disease has improved significantly during past decade, the treatment of intestinal BD is still problematic. Corticosteroids, sulfasalazine, immunomodulators, and colchicines have been used to treat intestinal BD with varying degree of success. Thalidomide and its analogues also appear to be applicable. Monoclonal antibodies to TNF-alpha have recently been focused as a novel therapeutic option for patients with intestinal BD.
Adrenal Cortex Hormones/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Behcet Syndrome/*drug therapy/*etiology ; Colchicine/therapeutic use ; Colitis, Ulcerative/*drug therapy/*etiology ; Crohn Disease/etiology ; Humans ; Immunologic Factors/therapeutic use ; Prognosis ; Sulfasalazine/therapeutic use ; Thalidomide/therapeutic use ; Tumor Necrosis Factor-alpha/immunology

A 66-year-old male with dyspepsia and weight loss was referred to our hospital for evaluation. On laboratory examination, anti-saccharomyces cerevisiae (ASCA)-IgA was positive and iron deficiency anemia was present. PET/CT and abdominal CT scan images showed multiple small bowel segmental wall thickening and inflammation. Capsule endoscopy images showed multiple small bowel ulcerative lesions with exudates. Based on laboratory test results and imaging studies, the patient was diagnosed with Crohn's disease and treated with prednisolone and 5-aminosalicylic acid (5-ASA). However, the patient underwent second operation due to small bowel perforation within 2 month after initiation of treatment. Pathology report of the resected specimen was compatible to primary small bowel diffuse large B cell lymphoma and pertinent treatment was given to the patient after recovery. Herein, we describe a case of primary small bowel diffuse large B cell lymphoma that was mistaken for Crohn's disease.
Aged ; Antibodies/blood ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Capsule Endoscopy ; Crohn Disease/diagnosis/drug therapy ; Diagnostic Errors ; Humans ; Immunoglobulin A/blood ; Intestinal Perforation/surgery ; Lymphoma, Large B-Cell, Diffuse/*diagnosis/drug therapy/pathology ; Male ; Mesalamine/therapeutic use ; Positron-Emission Tomography ; Saccharomyces cerevisiae/immunology ; Tomography, X-Ray Computed