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There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

Cytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n = 13) and inactive (n = 12) ulcerative colitis (UC), active (n = 11) and inactive (n = 11) Crohn's disease (CD) and in control patients (n = 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P < 0.001) and active CD (P < 0.005) compared with control patients. IFN-gamma mRNA concentrations were also significantly increased both in patients with active UC (P < 0.02) and active CD (P < 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P < 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease.

Background: Genetic susceptibility of celiac disease is primarily associated with a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully account for the genetic predisposition. Therefore, the aim of this study was to examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac disease., Methods: HLA class II typing was performed by polymerase chain reaction amplification in combination with sequence-specific oligonucleotide hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis., Results: Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between patients with celiac disease (n = 53) and control patients (n = 67), and relative risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35 for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at TCRB, showing no significant association. Additionally, linkage analysis was performed in 23 families. The logarithm of odd scores for celiac disease vs. the TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage., Conclusions: These data suggest that the analyzed TCR variable gene segments V alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to celiac disease.

Differentiation between malignant and nonmalignant ascites by means of laboratory parameters has so far not been completely achieved. One hundred and four patients with ascites (34 malignant, 51 cirrhotic, and 19 other) were studied for fibronectin concentration in ascites. The first 47 patients (13 malignant and 34 cirrhotic) were used to determine mean values and standard deviation (178 +/- 96 vs. 8.3 +/- 15.3 micrograms/ml) and to define a cutoff concentration between both groups (75 micrograms/ml). Several other parameters were analyzed simultaneously in these patients (total protein: 3.93 +/- 1.46 vs. 1.50 +/- 1.02 g/dl; white cell count: 2022 +/- 1153 vs. 569 +/- 405/mm3; lactic acid: 3.86 +/- 2.57 vs. 1.83 +/- 0.72 mmol/L; lactic acid dehydrogenase: 357 +/- 329 vs. 61 +/- 35 U/L; serum/ascites ratio of lactic acid dehydrogenase: 1.11 +/- 1.13 vs. 4.06 +/- 2.00; pH: 7.275 +/- 0.229 vs. 7.513 +/- 0.042). Their accuracy (mean of sensitivity and specificity) was always less than 87% due to a considerable overlap between both groups. Five patients with other causes of ascites could not be classified at all. Application of fibronectin determination on the subsequent 57 patients (21 malignant, 17 cirrhotic, and 19 other) revealed a sensitivity, specificity, and negative and positive accuracy for malignant ascites of 100%. Calculation of these parameters for all 104 patients gave identical values. The inclusion of 3 patients without final diagnosis in the group of nonmalignant ascites reduced specificity to 97.1 and positive accuracy to 94.4%. However, these values were superior to all other methods used so far. Fibronectin determination in ascites in combination with other parameters suitable for exclusion of infectious or pancreatic origin of ascites may prove useful in the differential diagnosis of ascites.

By using a four-step procedure (i, solubilization with Triton X-100; ii, affinity chromatography on concanavalin A-Sepharose; iii, affinity chromatography on wheat germ lectin-Sepharose; iv, preparative sodium dodecyl sulfate gel electrophoresis) a glycoprotein was isolated from rat liver plasma membrane. The molecular weight is 110,000 and the isoelectric point is 5.8. It contains L-fucose, N-acetylneuraminic acid, D-galactose, D-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and considerable quantities of aspartate, threonine, serine, and leucine. In pulse-chase experiments the half-lives of methionine and arginine, representing the half-life of the protein, were determined as 70 hr and 78 hr, respectively. The half-lives of the terminal carbohydrates L-fucose and N-acetylneuraminic acid were 12.5 and 33 hr, respectively. The galactose half-life was 20 hr. From this it is concluded that terminal sugars turn over several times in the life-span of this protein molecule. This process may be operative during membrane recycling mechanisms.

Dipeptidylaminopeptidase IV, a plasma membrane-bound glycoprotein, is characterized by an intramolecular heterogeneous turnover of the protein backbone and carbohydrate chain. The faster turnover of the latter is restricted only to the outer sugars. The inner core sugars D-mannose and N-acetyl-D-glucosamine turn over at the same rate as the protein backbone.