Beta2 integrin/ICAM expression in Crohns disease.
Bernstein CN. Sargent M. Gallatin WM.
Department of Medicine, University of Manitoba, Winnipeg, Manitoba, R3A 1R9, Canada.
We have previously reported on the expression of the beta2 integrin family of adhesion molecules and their ligands, the ICAM molecules, in the normal human intestine. These molecules likely have a role to play in the inflammatory response and, therefore, were studied in a group of patients with Crohn's disease. A comprehensive study was undertaken in both colon (n = 8) and ileum (n = 10) specimens from 15 patients who underwent surgical resections. Immunohistochemistry was performed for CD18, CD11a, CD11b, CD11c, alphad, ICAM-1, ICAM-2, and ICAM-3. Each of the mucosal, submucosal, muscle, and adventitial layers were scored for expression. Specimens from normal colon (n = 15), normal ileum (n = 6), and ulcerative colitis (n = 7) were used for comparisons. Compared with normal, the expression in the colon mucosa and submucosa in Crohn's disease was increased for all beta2 integrins. Mucosal CD11c expression was significantly greater in Crohn's disease than in ulcerative colitis. In the colon muscle and adventitial layers the expression in Crohn's disease was similar to normal but increased compared with ulcerative colitis. In Crohn's disease ileum, the beta2 integrin mucosal and submucosal expression was similar to normal; however, muscle and adventitial expression was increased, particularly for CD11c. Colon ICAM-1, ICAM-2, and ICAM-3 expression in Crohn's disease was similar to that seen in ulcerative colitis. ICAM-1 was predominantly expressed on endothelium but in the inflammatory bowel diseases was also evident on mucosal mononuclear cells. ICAM-1 and ICAM-2 expression was increased in Crohn's disease colon and ileum compared with normals. This was most notable in ileal mucosa since ICAM-2 is typically absent in normal ileal mucosa. In summary, we are reporting a comprehensive immunohistochemical study of the differential expression of beta2 integrins, including the newly described alphad molecule, and the ICAM molecules in all layers of the colon and ileum from patients with Crohn's disease. The increased expression of these molecules may have implications for therapeutic interventions in Crohn's disease.
Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection.
Tsai JF. Margolis HS. Jeng JE. Ho MS. Chang WY. Hsieh MY. Lin ZY. Tsai JH.
Department of Internal Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
For assessing the role of circulating immune complexes (CIC) in chronic hepatitis B virus (HBV) infection, CICs containing IgM, IgG, and HBsAg were determined by C1q and conglutinin (K) assays in 216 patients with chronic HBV infection and 54 healthy controls. The concentration of each type of CIC in patients is higher than in controls (P = 0.0001). CIC is a common feature of chronic HBV infection with 95.8% of cases having at least one abnormal test result. At least one type of HBsAg-CIC is positive in 54.2% of patients. HBsAg-CIC positivity is associated with HBeAg positivity (P = 0.0001), higher aminotransferase levels (P < 0.002), and younger age (P = 0.001). IgG-CIC or IgM-HBsAg-CIC correlates with higher aminotransferase activity (P = 0.001). In conclusion, HBsAg-CIC correlates with HBV replication. IgG-CIC and/or IgM-HBsAg-CIC correlate with disease activity. Immune-mediated injury may play a role in the pathogenesis of chronic HBV infection.
Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders.
Longombardo G. Ferri C. Marchi S. Costa F. Lombardini F. Vacri L. Bombardieri S. Migliorini P.
Clinical Immunology and Rheumatology Unit, University of Pisa, Italy.
NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.