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The introduction of new sensitive assays for the detection of HLA antibodies on basis of their binding to isolated HLA molecules has got an enormous impact on the decision-making process with respect to donor selection for sensitized patients. In the past, when only complement-dependent cytotoxicity was used as a tool to define HLA alloantibodies, the presence of donor specific antibodies (DSA) before transplantation was considered a contraindication for renal transplantation with that donor. The interpretation of the current DSA results is far more difficult and leads to a lot of discussions and controversy. The problems associated with the use of solid phase assays for clinical decision making and possible solutions are discussed. [ABSTRACT FROM AUTHOR]

In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/ B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27IB*57, they target similar conserved areas of HIV1/SlVcpz. In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HlV-1/SlVcpz Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic. [ABSTRACT FROM AUTHOR]

Background: The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short-and long-term outcome in surviving children. Methods/Design: We set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion. The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR). All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness. Discussion: The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance [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]