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Objective. Coeliac disease (CD) is associated with HLA-DQ2 and DQ8. The clinical picture is variable and certain human leucocyte antigen (HLA) DQ/DR combinations have a higher relative risk (RR) for CD than others. Moreover, the HLA-DQ gene-dose effect has an impact on the strength of the gluten-specific T-cell response and thus may correlate with clinical presentation and severity of CD. The aim of this study was to determine the correlation between HLA-DQ/DR-based genotypes and the variation in phenotypes of the disease. Material and methods. A total of 113 non-related Caucasian children clinically diagnosed with CD during the period 1980-2003 with a known HLA type were included in the study. Patients were divided into four categories according to amount of disease expression predisposing to HLA-DQ2 or HLA-DQ8 molecules and the known RR of their HLA-DR/DQ type for CD: high (DR3DQ2 homozygous and DR3DQ2/DR7DQ2), substantial (DR3DQ2/DR5DQ7 and DR5DQ7/DR7DQ2), moderate (DR3DQ2-DR4DQ8 and DR3DQ2/DR*DQ*) and low (DR7DQ2/DR*DQ*, DR4DQ8- DR*DQ* and DR*DQ*- DR*DQ*). The clinical data and HLA genotypes of these patients were compared. Results. The 113 children were diagnosed with CD at a mean age of 4.6 years and boys were significantly older than girls when diagnosed (p=0.01). RR for having CD was highest for the high HLA-risk group (RR 8.1). With the exception of a greater frequency of abdominal distension and fewer non-gastrointestinal symptoms in the substantial HLA-risk group, there were no significant differences in clinical characteristics or degree of severity of the small-bowel histological findings between the children in the different HLA-risk groups. Conclusion. No correlation was found between disease severity and a double HLA-DQ2 gene dose. [ABSTRACT FROM AUTHOR]

The DRB region of the MHC in primate species is known to display abundant region configuration polymorphism with regard to the number and content of genes present per haplotype. Furthermore. depending on the species studied, the different DRB genes themselves may display varying degrees of allelic polymorphism. Because of this combination of diversity (differential gene number) and polymorphism (allelic variation), molecular typing methods for the primate DRB region are cumbersome. All intact DRB genes present in humans and rhesus macaques appear to possess, however, a complex and highly divergent microsatellite. Microsatellite analysis of a sizeable panel of outbred rhesus macaques. covering most of the known Mamu-DRB haplotypes, resulted in the definition of unique genotyping patterns that appear to be specific for a given haplotype. Subsequent examination of a representative panel of human cells illustrated that this approach also facilitates high-resolution HLA-DRB typing in an easy, quick, and reproducible fashion. The genetic composition of this complex microsatellite is shown to be in concordance with the phylogenetic relationships of various HLA-DRB and Mamu-DRB exon 2 gene/lineage sequences. Moreover, its length variability segregates with allelic variation of the respective gene. This simple protocol may find application in a variety of research avenues such as transplantation biology, disease association studies, molecular ecology, paternity testing, and forensic medicine. [ABSTRACT FROM AUTHOR]

The MICA gene encodes for major histocompatibility complex class I chain-related proteins (MIC), which belong to a recently identified new family of nonclassical major histocompatibility complex molecules. The general structure of the MICA molecule resembles that of major histocompatibility complex class I molecules. MIC molecules are considered to be stress-induced antigens that are recognized by cytotoxic T cells and natural killer cells, which play an important role in the surveillance of transformed infected and damaged cells. Associations of major histocompatibility complex class I molecules with skin cancer have been described before. To evaluate the possible association of MICA gene polymorphism with the risk for nonmelanoma skin cancer we evaluated 153 cases with squamous cell carcinoma, 261 cases with basal cell carcinoma, 111 controls with malignant melanoma, and 247 controls without a history of skin cancer. Five distinct MICA alleles A4, A5, A6, A9, and A5.1 were studied. As the MICA 5.1 variant gene contains a four-nucleotide insertion that causes a stop codon in the trans membrane region, the resulting truncated MICA molecule does not reside on the cellular membrane. In the case of individuals who are homozygous for MICA 5.1 this results in cells that are naked for the MICA molecule. We therefore specifically addressed the possible association between MICA 5.1 homozygosity and skin cancer, as these individuals are expected to be at the highest risk for skin cancer if the MICA gene plays a role in skin carcinogenesis. Viral proteins may serve as antigens for recognition of skin cancer by the immune system. Human papillomavirus is the most likely candidate virus to be involved in the carcinogenesis of cutaneous squamous cell carcinoma. Hence, we also assessed the association between MICA polymorphism and squamous cell carcinoma in human-papillomavirus-positive and human-papillomavirus-negative individuals as identified by the presence of human... [ABSTRACT FROM AUTHOR]