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Soluble HLA-DR molecules in patients with HLA class II versus class I associated disorders.

HLA genes have been identified as key genetic factors contributing to many chronic diseases characterized by autoimmune features. The role of HLA encoded molecules in the pathogenesis of these diseases is unresolved. We have now analysed soluble HLA-DR molecules circulating in the serum of patients with different autoimmune diseases and have defined parameters controlling serum levels. Patients with HLA-DR associated diseases were characterized by elevated serum concentrations of HLA-DR molecules and were clearly distinct from patients with HLA-B27 associated disorders. We did not find evidence for a correlation between disease activity, laboratory abnormalities and elevated serum concentrations of soluble HLA-DR molecules. Studies in normal individuals indicated that soluble HLA-DR molecules are at least partially regulated by the HLA haplotype. Highest serum concentrations were found in individuals carrying the HLA-DR3 or HLA-DR4 haplotype raising the possibility that the phenomenon of HLA-disease association reflects differences in the genetic control of soluble HLA-DR molecules. Interferon-gamma treatment caused an increase in serum concentrations of soluble HLA-DR molecules, whereas a decrease of circulating HLA-DR molecules was associated with an immunosuppressive with cyclosporine A. These data suggest that the patient's immunoresponsiveness represents a second important mechanism controlling circulating HLA-DR molecules.

Arthritis, Psoriatic↗

Generation of NY-ESO-1-specific CD4+ and CD8+ T cells by a single peptide with dual MHC class I and class II specificities: a new strategy for vaccine design.

The existence of overlapping CD8+ and CD4+ T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+ T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO:157-170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8+ and CD4+ T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after in vitro stimulations using ESO:157-170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells.

Amino Acid Sequence↗

HLA class I and class II polymorphism in the population of Rijeka, Croatia.

The aim of the study was to examine frequencies of HLA-A, -B, -DR antigens and haplotypes in population of Rijeka and to compare them with general Croatian and European populations. The subjects were 117 unrelated healthy blood donors. The antigens with the highest frequencies were: A2 (27.2%), A9 (16.3%), B5 (14.8%), B12 (11.8%), B18 (11.8%), DR5 (21.6%) and DR6 (13.8%). Comparison of HLA antigens frequencies has shown statistically significant difference in 1 antigen with Croatian population and in 8 antigens with European population. The HLA haplotypes with high frequencies included HLA-A2, B5 (6.84%), HLA-A2, B12 (6.84%), HLA-A2, B18 (6.84%), HLA-B12, DR2 (9.78%) and HLA-B18, DR5 (6.84%). The antigen B5 showed strongest association with DR5 (6.41%; LD = 1.30) as in general Croatian and in some European populations. The results have shown great diversity of HLA haplotypes in Rijeka population which can be the result of admixture with neighborhood immigrating populations during the history.

Croatia↗

Anaerobic microflora under Class I and Class II composite and amalgam restorations.

OBJECTIVES: The microflora around and beneath restorations is an important factor of restoration failure. The aim of this pilot study was to determine and compare the microbial spectrum under composite and amalgam restorations with special attention to the anaerobic flora. METHOD AND MATERIALS: Ten composite and five amalgam restorations scheduled for replacement were clinically evaluated for marginal gaps, fractures, and secondary caries. After their removal and caries diagnosis, a dentin sample just below the restoration was taken under sterile conditions, stored in a prereduced transport medium for anaerobic bacteria, and immediately transferred to a laboratory for microbial diagnosis. RESULTS: The clinical parameters showing mostly moderate marginal imperfections and the ratios of aerobic to anaerobic flora were comparable for composite and amalgam restorations (11.4%:88.6% and 15.4%:84.5%, respectively). The microbial variety under composite restorations was much greater compared to amalgam, and it was similar to that of infected root canals including anaerobic gram-negative rods, such as Fusobacterium species or Porphyromonas species. Beneath amalgam, the microbial flora was similar to the one found in carious dentin and plaque, with anaerobic and facultatively anaerobic gram-positive rods dominating. Quantitatively, there were up to eight times more microorganisms under composite restorations. The number of bacterial strains correlated with the caries activity and the filling material, the number of anaerobic rods correlated highly with caries activity and localization. In a linear regression, caries activity and the filling material had statistically significant influence on the bacterial load. CONCLUSION: Although caries activity and location had the greatest influence on the microbial flora under the restorations, the kind of restoration material seemed to have an additional effect on the composition of the microflora. This pilot study indicates that inadequate composite restorations may promote the growth of cariogenic, as well as obligate anaerobic and potentially pulpopathogenic bacteria, which should be confirmed by further studies.

Bacteria, Aerobic↗