Antibody markers in the diagnosis of inflammatory bowel disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD.

Possible diagnostic role of antibodies to Crohn's disease peptide (ACP): results of a multicenter study in a Japanese cohort.

BACKGROUND: Various noninvasive tests have been studied to screen for patients with Crohn's disease (CD), and were found to have limited accuracy and sensitivity, particularly in Asian populations. The aim of our study was to explore the possible diagnostic utility of antibodies to the CD peptide (ACP) in patients with CD. METHODS: In a multicenter study using enzyme-linked immunosorbent assay, serum ACP levels were determined in 196 patients with CD, 210 with ulcerative colitis, 98 with other intestinal diseases, 132 with other inflammatory diseases, and 183 healthy controls. and then examined for correlation to clinical variables. The diagnostic utility of ACP was evaluated by receiver operating characteristics analysis and compared with anti-Saccharomyces cerevisiae antibodies (ASCA). RESULTS: ACP levels were significantly elevated in the CD patients, but not in the other groups that included UC, other intestinal diseases, other inflammatory diseases and the healthy controls. Among these other groups, ACP levels were not significantly different. In the CD patients, ACP had a higher sensitivity and specificity (63.3 and 91.0 %, respectively) than ASCA (47.4 and 90.4 %). ACP levels were negatively associated with disease duration, but not with CDAI, disease location, or medical treatment. CONCLUSIONS: ACP, a newly proposed serologic marker, was significantly associated with CD and was highly diagnostic. Further investigation is needed across multiple populations of patients and ethnic groups, and more importantly, in prospective studies.

Efficient isolation of cDNA clones encoding rheumatoid arthritis autoantigens by lambda phage surface display.

Bacteriophage lambda surface display was used to isolate cDNA clones encoding autoantigens recognized by synovial fluid (SF) or sera from patients with rheumatoid arthritis (RA). We constructed cDNA libraries from human synovial sarcoma cells and synovial tissue, using the surface display vector lambdafoo. The cDNA libraries were screened by affinity selection using 40 SF and 44 sera as probes separately immobilized in microtiter wells. Phage clones isolated encode 13 different autoantigens; an unknown protein, two proteins previously unanalyzed as autoimmune antigens, three proteins previously unknown to be recognized by RA sera, and seven known RA antigens. When analyzed their sensitivity and specificity for RA by phage enzyme-linked immunosorbent assay, frequencies of sera that recognize the newly-isolated autoantigens ranged from 20.5 to 6.8% of a panel of RA sera, and 13.6-0% of other autoimmune disease sera. These results indicate that the lambda phage surface display may be powerful for the isolation of cDNA clones encoding autoantigens recognized by SF or sera from patients with not only RA but also other autoimmune diseases.

CD147 and matrix metalloproteinase-2 protein expression as significant prognostic factors in esophageal squamous cell carcinoma.

BACKGROUND: The authors investigated whether the presence of matrix metalloproteinase-2 (MMP-2) and its inducer, CD147, in cancerous esophageal lesions and surrounding tissue might help to predict patient prognosis. METHODS: Tissue samples from 101 patients with esophageal squamous cell carcinoma were stained with anti-CD147 and anti-MMP-2 antibodies for immunohistochemical analysis. RESULTS: CD147 was expressed in cancerous and dysplastic lesions, but not in normal tissue. In contrast, MMP-2 was detected mainly in normal interstitial tissue adjacent to cancerous lesions, but it was detected also in cancerous lesions in some patients. Pathologic findings demonstrated that the intensity of MMP-2 staining in normal tissue was associated positively with the depth of tumor infiltration and the stage of disease, whereas MMP-2 staining in cancerous tissue was associated positively with vascular and lymphatic vessel invasion as well as with immature differentiation of cancer cells. Using a proportional hazard model, including information on CD147 staining patterns within cancerous lesions along with clinical cancer staging, improved the accuracy of predicting patient prognosis. CONCLUSIONS: These results suggested that measurement of CD147 and MMP-2 expression with simple immunohistochemical staining may enhance further the understanding of the pathophysiology of invading tumor cells and, when used in combination with cancer staging, may increase the ability of investigators to predict prognosis in patients with esophageal squamous cell carcinoma.