Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope.

OBJECTIVE: To investigate the presence of the Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) synovium and its correlation with the HLA genotype in an attempt to elucidate the role of EBV in the pathogenesis of RA. METHODS: EBV DNA/RNA was investigated by polymerase chain reaction (PCR) analysis of synovial tissue from 84 patients with RA and from 81 patients with non-RA arthritis (controls) and was correlated with the patients' HLA genotype. RESULTS: EBV DNA and EBV-encoded RNA 1 transcripts were significantly more frequently present in synovial tissue from the RA patients (29 of 84) than in that from the non-RA patient controls (8 of 81). EBV DNA-positive individuals had a 5.47 times higher risk of presenting with RA than did EBV DNA-negative individuals. In HLA-DRB1*0401,0404,0405,0408-positive or shared epitope-positive patients, the risk was further increased (odds ratio for EBV and HLA-DR4 approximately 41, for EBV and the shared epitope approximately 15) compared with those who lacked both EBV DNA and RA-linked HLA genotypes. CONCLUSION: EBV seems to function as an environmental risk factor for RA, particularly in patients with the RA-linked HLA-DRB1 alleles.

Cytomegalovirus monitoring by polymerase chain reaction of whole blood samples from patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation.

Sensitive screening for cytomegalovirus (CMV) by polymerase chain reaction (PCR) following autologous bone marrow or peripheral blood progenitor cell transplantation has not been evaluated. In a three-center study, 98 autograft transplant recipients were prospectively screened for CMV infection by PCR and culture techniques. At a median of 20 days (range, 3-28) after transplantation, 21 (39.6%) of 53 CMV-seronegative patients were PCR positive for CMV, and at a median of 17 days (range, 7-84) after transplantation, 19 (42.2%) of 45 CMV-seropositive patients were PCR positive for CMV. Low-level DNAemia (1-10 fg CMV DNA/mL blood) occurred for 1 week in 31 patients but was never associated with CMV disease. Of 9 patients who presented with at least two consecutive positive PCR results, 1 developed CMV pneumonia. No patients died because of CMV disease. Screening for CMV infection by PCR had a negative predictive value of 100% (as also observed after allogeneic transplantation), but its positive predictive value was significantly lower.

Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation.

Sixty-three recipients of an allogeneic marrow transplant were screened for the occurrence of cytomegalovirus (CMV) infection and clinical parameters possibly predicting the development of CMV disease in a retrospective study. Blood and urine samples obtained from these patients were screened weekly after bone marrow transplantation (BMT) for the presence of CMV by polymerase chain reaction (PCR) and virus culture technique. Forty-six of the 63 patients studied were found to be CMV-positive by PCR technique in blood and urine samples at a median of 29 days after BMT. In 33 of these 46 patients, CMV could be cultured from urine samples and 16 of the 46 had culture-positive viremia. Twenty-eight of these 46 PCR-positive patients developed CMV disease. Whereas PCR assays showed an optimal negative predictive value and sensitivity for the development of CMV disease, their positive predictive value was 61% and could not be remarkably increased when culture-proven viruria (64%) and viremia (69%) were considered. Acute graft-versus-host disease (GVHD) grade 2 to 4 (P < .05), but not underlying disease, conditioning therapy, or GVHD prophylaxis, was associated with CMV infection. On day +49, a remarkable decrease (P < .001) in the lymphocyte count, as well as in the absolute number of CD4+, CD8+, and CD56+ lymphocytes, occurred only among the patients who later developed CMV disease. The decrease of all of these cell counts, but predominantly the CD4+ T cells, to less than 100/microL on day +49 after BMT showed a very high positive predictive value (100%) for the development of CMV disease in patients with PCR-proven viremia. Persisting CD4 lymphopenia after antiviral therapy was only observed in patients who finally died of CMV disease. Thus, immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.

Data modeling for immunological and clinical data of leukemia and myasthenia patients.

In this study it was investigated whether and to what extent semantic data models and their methods for data modeling are useful for adequate representation and integration of immunological and clinical data. To that end the special research program in leukemia research and immunogenetics (SFB 120) of the University of Tübingen was taken as an example. Based on the semantic data model RM/T we propose the design of a database system, report on its realization, and discuss this approach. Using a semantic data model, the quality of data increased considerably. This means, for instance, that the integration of the molecular-biological knowledge allows a better control of the person-related results. Hence, the decisions based of these data may have greater validity and the treatment on leukemia patients can be improved. Furthermore, the elucidation of immune mechanisms concerning auto-immune diseases could be improved.

On research subsystems and their integration in the computer-supported part of hospital information systems.

Taking as an example the special research programme ('Sonderforschungsbereich') in leukemia research and immunogenetics (SFB120) of the University of Tübingen, we intend to discuss how research subsystems should be built up, which functions they should take over and which network architecture is suitable. Furthermore, we examined to what extent research subsystems can be integrated in the computer-supported part of hospital information systems. It can easily be seen that no general solution exists for the structuring. The structure depends rather upon the specific problems and information requirements of individual research units. The clinical environment must be taken into account if research subsystems are to be integrated into the computer-supported part of a hospital information system. Especially in regard to the data protection aspect, we must keep in mind that the connection between subsystems must not necessarily result in the setup of a network for the corresponding computer systems.