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CCR5 is a chemokine receptor expressed on T-cells and macrophages. A 32-base pair deletion in the chemokine receptor 5 gene (CCR5-Δ32) leads to a non-functional receptor. Conflicting evidence exists whether this deletion is associated with primary sclerosing cholangitis (PSC). We genotyped the CCR5-Δ32 variant in 363 PSC patients and 366 controls. No significant increase in the Δ32 allele frequency was detected in the PSC patients compared to controls (12.7% vs 10.7% OR = 1.22, 95% CI [0.88, 1.68], P = 0.23). Survival analysis did not reveal any significant effects from CCR5-Δ32 genotypes on disease progression. Thus, in this study (power > 90%, given OR = 2, α = 0.05), we were unable to replicate previous findings and our results do not support an involvement of CCR5-Δ32 in either PSC susceptibility or progression. [ABSTRACT FROM AUTHOR]

First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1*03 and DRB1*04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.Genes and Immunity (2006) 7, 130–140. doi:10.1038/sj.gene.6364272; published online 5 January 2006 [ABSTRACT FROM AUTHOR]

Background: The prevalence of hereditary hemochromatosis in Norway is one of the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patients with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. Methods: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum transferrin and ferritin concentrations were measured in all patients, and a percutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4[sup +] and fibrosis from 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was performed by PCR-RFLP. Results: Forty-eight (40%) of the patients suffered from tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 105 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patients referred from a blood bank had significantly less symptoms and signs compared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mutation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When excluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) were homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. Conclusions: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis in a majority of the C282Y mutation negative patients was associated with excessive oral iron intake for several years. [ABSTRACT FROM AUTHOR]

T cells from sensitized individuals react with a proliferative response to herpes simplex virus antigen (HSV-Ag) in vitro, when antigen is presented together with autologous macrophages (Mo). We here report that this T-Mo co-operation is restricted by self HLA-D/R molecules of the sensitized T cell donor. Furthermore, it is shown that the lack of co-operation between T cells and HLA-D/R disparate macrophages, is due neither to suppression nor to generation of cytotoxic T cells in the allogeneic mixture. [ABSTRACT FROM AUTHOR]

The abilities of human epidermal Langerhans cells and peripheral blood macrophages to induce specific T-lymphocyte responses to purified protein derivative (PPD), herpes simplex virus and nickel sulphate were compared. On a cell to cell basis the Langerhans cells were found to be about as potent as adherent cells in inducing T-cell responses to PPD, more potent in inducing responses to herpes simplex virus, and several times more potent in inducing responses to nickel. These data indicate that human epidermal Langerhans cells are highly specialized in antigen presentation, particularly for nickel sulphate. They may play an important role in inducing contact sensitivity dermatitis. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy is a heart muscle disease with an obscure aetiology. Data from four generations of a large family (71 members) are presented. The occurrence of hypertrophic cardiomyopathy among members of the two oldest generations was compatible with a pattern of autosomal dominant inheritance. Seven out of 14 siblings in the second generation had definite signs of or were clinically suspected of having hypertrophic cardiomyopathy. The severity and distribution of left ventricular hypertrophy varied, but three (21%) brothers in generation II showed the classic picture of left ventricular outflow obstruction. Four siblings (29%) died suddenly aged 11, 22, 38, and 40 years. A high incidence of the disease would have been expected in the two younger generations (41 members, aged 1-31 years), but only two, a 16 year old boy and a 17 year old girl had signs of asymmetric septal hypertrophy. Current diagnostic procedures, including M mode and cross sectional echocardiography, are not sufficiently sensitive to identify young family members who may have preclinical hypertrophic cardiomyopathy. No evidence for close genetic linkage between a postulated locus for hypertrophic cardiomyopathy and the major histocompatibility complex (antigens HLA-A, HLA-B, and HLA-DR) was found. [ABSTRACT FROM PUBLISHER]

A method is described where superparamagnetic polymer microspheres coated with monoclonal antibodies (MoAb) are used for the direct and fast quantification of the absolute number of cells of various lymphocyte subsets in blood. Blood samples were incubated with microspheres coated with a subset specific MoAb, Using a magnet the microsphere-rosetted cells were isolated and washed. Following lysis of the cell walls to detach the microspheres, the cell nuclei were stained with acridine orange and counted in a haemocytometer using an immunofluorescence microscope. With MoAb specific for CD2, CD4, CD8 and CD19, reproducible absolute counts of the corresponding lymphocyte subsets were obtained which correlated closely with those obtained by an indirect quantification method. [ABSTRACT FROM AUTHOR]

HLA-DR-like antigens and secretory component (SC) were localized immunohistochemically in adjacent issue sections of ethanol-fixed paraffin-embedded jejunal mucosa from control subjects and patients with coeliac disease (CD) or dermatitis herpetiformis (DH). HLA-DR-like antigens were found in a patchy distribution apically in the columnar epithelial cells facing the gut lumen and in the upper part of the crypt epithelium. The staining pattern was similar in controls and patients with CD or OH, SC was normally most abundant in the crypt epithelium hut the concentration of SC in the surface epithelium increased with increasing villous atrophy both in CD and DEL patients. Despite this sign of immaturity, the surface cells retained their capacity to express ELLA-DR-like antigens in the pathological mucosa. [ABSTRACT FROM AUTHOR]