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Leucocyte Antigen (leucocyte + antigen)
Kinds of Leucocyte Antigen Selected AbstractsINDUCTIVE RISK AND JUSTICE IN KIDNEY ALLOCATIONBIOETHICS, Issue 8 2010ANDREA SCARANTINO ABSTRACT How should UNOS deal with the presence of scientific controversies on the risk factors for organ rejection when designing its allocation policies? The answer I defend in this paper is that the more undesirable the consequences of making a mistake in accepting a scientific hypothesis, the higher the degree of confirmation required for its acceptance. I argue that the application of this principle should lead to the rejection of the hypothesis that ,less than perfect' Human Leucocyte Antigen (HLA) matches are an important determinant of kidney graft survival. The scientific community has been divided all along on the significance of partial antigen matches. Yet reliance on partial matches has emerged as one of the primary factors leading blacks to spend a much longer time than whites on the waiting list for kidneys, thereby potentially impacting the justice of the kidney allocation policy. My case study illustrates one of the legitimate roles non-epistemic values can play in science and calls into question the ideal of a value-free science. [source] Hypocretin/orexin and narcolepsy: new basic and clinical insightsACTA PHYSIOLOGICA, Issue 3 2010S. Nishino Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source] The clinical impact of pharmacogenetics on the treatment of epilepsyEPILEPSIA, Issue 1 2009Wolfgang Löscher Summary Drug treatment of epilepsy is characterized by unpredictability of efficacy, adverse drug reactions, and optimal doses in individual patients, which, at least in part, is a consequence of genetic variation. Since genetic variability in drug metabolism was reported to affect the treatment with phenytoin more than 25 years ago, the ultimate goal of pharmacogenetics is to use the genetic makeup of an individual to predict drug response and efficacy, as well as potential adverse drug events. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication. This article reviews the published work with particular emphasis on pharmacogenetic alterations that may affect efficacy, tolerability, and safety of antiepileptic drugs (AEDs), including variation in genes encoding drug target (SCN1A), drug transport (ABCB1), drug metabolizing (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins. Although the current studies associating particular genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions, several results, for example that Asian patients with a particular HLA allele, HLA-B*1502, are at a higher risk for Stevens-Johnson syndrome when using carbamazepine, are helpful to increase our knowledge how genetic variation affects the treatment of epilepsy. Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with epilepsy. [source] Alpha B-crystallin is not a dominant peripheral T-cell autoantigen in multiple sclerosis amongst SardiniansEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2003S. Sotgiu The heat shock protein alpha B-crystallin appears to be the dominantly recognized autoantigen in the early demyelinative process of multiple sclerosis (MS) in brain of patients. In Sardinia, MS is linked to human leucocyte antigen (HLA)-DR alleles that might influence the production of cytokines from peripheral lymphocytes. We tested the nature of peripheral anti-alpha B-crystallin-specific T-cell response in the context of predisposing HLA haplotypes both in MS patients and healthy controls. The alpha B-crystallin specific T-cell lines were generated by using the ,split-well' technique. The results indicate that the presence of short-term T-cell lines towards alpha B-crystallin is numerically comparable between the two groups and not restricted to MS-predisposing HLA-DR alleles. As for the T-cell characterization, CD4+ anti-alpha B-crystallin T cells secreting high levels of interferon- , are similarly identified in MS and healthy donors. In conclusion, the peripheral response towards the myelin antigen alpha B-crystallin is neither quantitatively nor qualitatively peculiar to MS, in contrast to the theoretical paradigm suggesting peripheral activation of myelin-reactive T cells to be the prerequisite for MS induction. [source] Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy1EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2002S. Sotgiu Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population. [source] Major histocompatibility complex class I binding predictions as a tool in epitope discoveryIMMUNOLOGY, Issue 3 2010Claus Lundegaard Summary Over the last decade, in silico models of the major histocompatibility complex (MHC) class I pathway have developed significantly. Before, peptide binding could only be reliably modelled for a few major human or mouse histocompatibility molecules; now, high-accuracy predictions are available for any human leucocyte antigen (HLA) -A or -B molecule with known protein sequence. Furthermore, peptide binding to MHC molecules from several non-human primates, mouse strains and other mammals can now be predicted. In this review, a number of different prediction methods are briefly explained, highlighting the most useful and historically important. Selected case stories, where these ,reverse immunology' systems have been used in actual epitope discovery, are briefly reviewed. We conclude that this new generation of epitope discovery systems has become a highly efficient tool for epitope discovery, and recommend that the less accurate prediction systems of the past be abandoned, as these are obsolete. [source] The extensive polymorphism of KIR genesIMMUNOLOGY, Issue 1 2010Derek Middleton Summary The functions of human natural killer (NK) cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin-like receptors (KIR), a family of genes clustered in one of the most variable regions of the human genome. Within this review we discuss the vast polymorphism of the KIR gene complex which rivals that of the human leucocyte antigen (HLA) complex. There are several aspects to this polymorphism. Initially there is presence/absence of individual KIR genes, with four of these genes, termed framework genes, being present in all individuals tested to date, except on those very occasional instances when the gene has been deleted. Within each gene, alleles are present at different frequencies. We provide details of a new website that enables convenient searching for data on KIR gene, allele and genotype frequencies in different populations and show how these frequencies vary in different worldwide populations and the high probability of individuals differing in their KIR repertoire when both gene and allele polymorphism is considered. The KIR genes present in an individual may be classified into A and/or B haplotypes, which respectively have a more inhibitory role or a more activating role on the function of the NK cell. Family studies have been used to ascertain the make-up of these haplotypes, inclusion of allele typing enabling determination of whether one or two copies of a particular gene is present. In addition to genetic diversification the KIR gene complex shows differences at the functional level with different alleles having different protein expression levels and different avidity with their HLA ligand. [source] Neuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancerIMMUNOLOGY, Issue 1 2008Alessandra Battaglia Summary We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25high T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1, Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1+ Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1, Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25int and CD25, CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1, counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1+ CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy. [source] HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2009G. Sulcebe Summary Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor,recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2-digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy,Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA-A-B-DRB1 haplotypes were A*02,B*18,DRB1*11 (5.60%), A*02,B*51,DRB1*16 (4.74%), A*01,B*08,DRB1*03 (3.48%), A*24,B*35,DRB1*11 (2.77%), A*02,B*51,DRB1*13 (2.21%), A*24,B*35,DRB1*14 (1.89%). Interestingly, 12 HLA-A-B-Cw-DRB1-DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area. [source] Analysis of high-resolution HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor,recipient confirmatory typingsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2009A.-L. Hei Summary High-resolution human leucocyte antigen (HLA)-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor,recipient confirmatory typings. A total of 28 HLA-A, 61 HLA-B, 30 HLA-Cw, 40 HLA-DRB1 and 18 HLA-DQB1 alleles were identified, and HLA-A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple-locus haplotype analysis by the maximum-likelihood method revealed 45 A,B, 38 Cw,B, 47 B,DRB1, 29 DRB1,DQB1, 24 A,B,DRB1, 38 A,Cw,B, 23 A,Cw,B,DRB1, 33 Cw,B,DRB1,DQB1 and 22 A,Cw,B,DRB1,DQB1 haplotypes with frequencies >0.5%. The most common two-, three-, four- and five-locus haplotypes in this population were: A*0207,B*4601 (7.34%), Cw*0102,B*4601 (8.71%), B*1302,DRB1*0701 (6.19%), DRB1*0901,DQB1*0303 (14.27%), A*3001,B*1302,DRB1*0701 (5.36%), A*0207,Cw*0102,B*4601 (7.06%), A*3001,Cw*0602,B*1302,DRB1*0701 (5.36%), Cw*0602,B*1302,DRB1*0701,DQB1*0202 (6.12%) and A*3001,Cw*0602,B*1302,DRB1*0701,DQB1*0202 (5.29%). Presentation of the high-resolution alleles and haplotypes data at HLA-A, -B, -Cw, -DRB1 and -DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population. [source] Comparison of IL10 and IL2 genotypes of Turkish population with other populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2009A. C. Yaz Summary The human genome has been shaped by evolutionary and historical forces. Therefore, genetic polymorphisms are useful tools not only to understand the susceptibility to disease in modern populations, but the history of ancestral populations as well. For this purpose, data on genetic polymorphisms such as human leucocyte antigen, mitochondrial DNA sequence variability and the frequencies of TAP1 and TAP2 gene variants in Turkey have been reported previously. Here we have used interleukin (IL)-10 (,592C/A, ,819T/C, ,1082G/A) and IL-2 (,330T/G) as genetic markers to study the relationship between Turkish population and other populations. [source] HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance?INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2008E. Albanidou-Farmaki Summary The aim of this study was to investigate the genetic association between recurrent aphthous stomatitis (RAS) and human leucocyte antigen (HLA) class I and II alleles and HLA haplotypes. Families selected had at least one child suffering from recurrent aphthous stomatitis in addition to one or both of the parents. HLA-A, -B and -DR alleles were typed in 29 families, 27 nuclear and two extended (121 subjects). HLA haplotypes of all family members with RAS were compared with those who were RAS negative. Although major histocompatibility complex class I and II gene analysis failed to demonstrate any significant association between RAS and HLA antigens, the study of HLA haplotypes revealed a significant association between HLA haplotypes and susceptibility to RAS. The results indicate that susceptibility to RAS segregates in families in association with HLA haplotypes. [source] Sequence-based characterization of the eight SLA loci in Korean native pigsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008Y. J. Lee Summary Eight swine leucocyte antigen (SLA) gene (SLA-1, SLA-2, SLA-3, SLA-6, DRA, DRB1, DQA, DQB1) alleles were identified using sequence-based typing method in three Korean native pigs used for breeding at the National Institute of Animal Science in Korea. Six new alleles in class I genes and three new alleles in class II genes have been identified in this breed and can give valuable information for xenotransplantation and disease resistance. [source] Distribution of killer cell immunoglobulin-like receptor genes in PolesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008E. Majorczyk Summary Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leucocyte antigen (HLA) molecules on the surface of target cells. Humans differ by the presence or absence of some KIR genes on their chromosomes. As KIRs are important for the outcome of tissue transplantation (particularly for haematopoietic stem cell transplantation) and possibly for pregnancy and autoimmune diseases, knowledge of the KIR gene distribution in a given human population is of practical value. Therefore, we tested 363 healthy individuals from Western Poland for the presence or absence of KIR genes. Results are compared with those published for other human populations. KIR gene frequencies in Poles are close to these in other Caucasoids but different from those in Asian and African populations, and particularly distant from those in Australian Aborigines. [source] Discovery of HLA-B*480102 in TaiwaneseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008M. J. Chen Summary Human leucocyte antigen (HLA)-B48, an antigen within 7C CREG (cross-reacting group) (Steiner et al., 2001) that cross-reacts frequently with HLA-B40 (i.e. HLA-B60 and -B61) group of antibodies serologically, can be found in Alaskan Natives (Leffell et al., 2002), Amerindians (Martinez-Naves et al., 1997), African Americans, Caucasians, and Oriental ethnicities (Mori et al., 1997; Schipper et al., 1997; Cao et al., 2001; Middleton et al., 2004; Hong et al., 2005; Itoh et al., 2005; Lee et al., 2005; Ogata et al., 2007). Sequencing investigations demonstrated that the common allele encoding the B48 antigen is B*4801 (Belich et al., 1992). To date, there are at least 16 WHO recognized B*48 alleles according to the most recent report from the WHO nomenclature committee (Marsh et al., 2005). Here we report a newly discovered allele B*480102, a variant of B*4801, detected in a 55-year-old Taiwanese patient of Minan origin (southern China). [source] Lack of association between HLA-A, -B and -DRB1 alleles and the development of SARS: a cohort of 95 SARS-recovered individuals in a population of Guangdong, southern ChinaINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008P. Xiong Summary Severe acute respiratory syndrome (SARS), caused by infection with a novel coronavirus (SARS-CoV), was the first major novel infectious disease at the beginning of the 21st century, with China especially affected. SARS was characterized by high infectivity, morbidity and mortality, and the confined pattern of the disease spreading among the countries of South-East and East Asia suggested the existence of susceptible factor(s) in these populations. Studies in the populations of Hong Kong and Taiwan showed an association of human leucocyte antigen (HLA) polymorphisms with the development and/or severity of SARS, respectively. The aim of the present study was to define the genotypic patterns of HLA-A, -B and -DRB1 loci in SARS patients and a co-resident population of Guangdong province, southern China, where the first SARS case was reported. The samples comprised 95 cases of recovered SARS patients and 403 unrelated healthy controls. HLA -A, -B and -DRB1 alleles were genotyped using polymerase chain reaction with sequence-specific primers. The severity of the disease was assessed according to the history of lung infiltration, usage of assisted ventilation and occurrence of lymphocytopenia. Although the allelic frequencies of A23, A34, B60, DRB1*12 in the SARS group were slightly higher, and A33, -B58 and -B61 were lower than in the controls, no statistical significance was found when the Pc value was considered. Similarly, no association of HLA alleles with the severity of the disease was detected. Thus, variations in the major histocompatibility complex are unlikely to have contributed significantly to either the susceptibility or the severity of SARS in the population of Guangdong. [source] Determination of HLA-A, -B and -DRB1 haplotypes based on allelic homozygosity data in selected bone marrow donors of the Taiwanese marrow donor registryINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2007K. L. Yang Summary From 120 unrelated Taiwanese marrow stem cell donors with allelic homozygosities at human leucocyte antigen (HLA)-A, -B and -DRB1 loci, we determined 85 distinguishable haplotypes. Using the predetermined haplotype data, we deduced 418 haplotypes from 1903 unrelated individual stem cell donors selected for HLA confirmatory test. Eighteen of the 20 (90%) most frequently observed haplotypes determined in Asian Americans using computer prediction were found in this study. In comparison with haplotypes determined by maximum likelihood algorithm in Korean population, 18 of the 29 (62.07%) Korean haplotypes with a frequency over 0.5% were also among the haplotypes determined in this investigation. Randomized family studies confirmed that over 50% of the haplotypes observed in the families were among the haplotypes deduced based on allelic homozygosity, suggesting that proportionally additional haplotypes can be determined as the number of donors being studied is increased. Haplotypes carrying low incidence allele characteristics of Taiwanese were also observed in this study. This established haplotype information will be beneficial for patients searching for stem cell donors in our registry domestically and internationally. [source] A survey of H2 gene sequences, including new wild-derived genesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2007N. A. Mitchison Summary A comprehensive collection of mouse major histocompatibility complex (MHC) promoter and exon 2 sequences is here presented and analysed. It covers the three best known class II genes and one class I gene, and includes new wild mouse sequences from the ,w' back-cross strains and from the Jackson collection. All sequences are in GenBank, and the new exon sequences largely confirm previous typing by serology and immune function. As in human leucocyte antigen (HLA), the overall nucleotide diversity is higher in the class II genes, in keeping with their more diverse function. Diversity along the promoters is highest in the region of known transcription factor binding, most notably in and around the CRE and rCAAT sequences. This distribution parallels that of maximum single nucleotide polymorphism impact previously obtained with reporter constructs. Taking into account the low nucleotide diversity of the CIITA promoter, we conclude that MHC promoters are likely to have diversified through co-evolution with their exons, while themselves also directly subject to natural selection. The H2Ebp alleles form a distinct group, associated with their lack of the recombination hot spot located between exon 2 and exon 3. The collection is expected to prove useful in guiding functional and evolutionary studies. [source] Molecular diversity of HLA-A*19 group of alleles in south Indian populationINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2006V. Vettriselvi Summary To determine the genetic diversity of the human leucocyte antigen (HLA)-A*19 group of alleles in the south Indian Tamil population, we studied 100 random healthy unrelated individuals. The frequency of HLA-A*19 was 37% with A*33 (45.9%), A*32 (29.7%), A*31 (16.2%), A*30 (5.4%), A*29 (2.7%) and A*74 (0%). The frequency distribution of the HLA-A*19 alleles was distinct and revealed marked similarities and variations with other populations [source] HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006W. H. Yan Summary Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal,fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal,maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA. [source] Identification of therapeutically relevant mHags and strategies for mHag-based immunotherapy after allogeneic HSCT: where do we stand?ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010B. Eiz-Vesper Minor histocompatibility antigens (mHags) play a major role in graft-versus-host disease (GvHD) and graft-versus-leukaemia (GvL) effect following human leucocyte antigen (HLA)-matched hematopoietic stem cell transplantation (HSCT). These antigens are defined as immunogenic peptides derived from polymorphic proteins and can be recognized by allogeneic cytotoxic T cells (CTLs) in the context of HLA molecules. The tissue distribution of mHags and HLA molecules influences the clinical outcome of T-cell responses to these antigens. Differential T-cell recognition of mHags specifically expressed in hematopoietic cells, including malignant cells from the recipient, may result in a beneficial GvL effect without detrimental GvHD. Furthermore, T-cell responses against proteins solely expressed in hematopoietic cell lineages from which the malignancy is derived may be appropriate mediators of GvL reactivity without GvHD induction. mHags with hematopoiesis-restricted expression may therefore serve as primary targets of the T-cell-mediated GvL/graft-versus-tumour (GvT) effect following HLA-identical HSCT. This paper reviews the recent findings on methods for identification of mHags specifically functioning as GvL/GvT targets and outlines perspectives for the development of novel strategies for mHag-based immunotherapy. [source] Canine diabetes mellitus: from phenotype to genotypeJOURNAL OF SMALL ANIMAL PRACTICE, Issue 1 2008B. Catchpole Breed differences in susceptibility to diabetes mellitus in dogs suggest an underlying genetic component to the pathogenesis of the disease. There is little evidence for an equivalent of human type 2 diabetes in dogs, and it has been proposed that canine diabetes is more comparable to the type 1 form of the disease. Certain immune response genes, particularly those encoding major histocompatibility complex molecules involved in antigen presentation, are important in determining susceptibility to human type 1 diabetes. We tested the hypothesis that canine major histocompatibility complex genes (known as the dog leucocyte antigen) are associated with diabetes in dogs. A total of 530 diabetic dogs and more than 1000 controls were typed for dog leucocyte antigen, and associations were found with three specific haplotypes. The DLA-DRB1*009/DQA1*001/DQB1*008 haplotype shows the strongest association with diabetes in the UK dog population. This haplotype is common in diabetes-prone breeds (Samoyed, cairn terrier and Tibetan terrier) but rare in diabetes-resistant breeds (boxer, German shepherd dog and golden retriever), which could explain differences in the prevalence of diabetes in these different breeds. There is evidence that the DLA-DQA1*001 allele is also associated with hypothyroidism, suggesting that this could represent a common susceptibility allele for canine immune-mediated endocrinopathies. [source] Study on association between polymorphism of HLA-DRB1 alleles and Behçet's diseaseJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 12 2009Y-B Shang Abstract Background, Behçet's disease (BD) is known to be associated with human leucocyte antigen (HLA)-B*51 in many ethnic groups. However, the association of HLA class II gene with BD has been described to be different according to different countries and regions. Objective, This study aims to investigate the association between polymorphism of HLA-DRB1 alleles and BD. Methods, Forty patients with BD and 100 healthy controls were typed for HLA-DRB1 alleles by the LABTypeTM SSO method. Results, The frequency of HLA-DRB1*14 was significantly higher in BD patients than in controls (P < 0.05), while the frequency of HLA-DRB1*15 was markedly lower in BD patients (P < 0.05). Regarding clinical manifestations, the frequency of HLA-DRB1*15 was significantly decreased in BD patients with genital ulcerations compared with controls (P < 0.05); the frequency of HLA-DRB1*14 was significantly increased in BD patients with erythema nodosum,like lesions and in BD patients with folliculitis-like lesions when compared to controls (P < 0.05, respectively). Moreover, the frequency of HLA-DRB1*14 was significantly increased in BD patients under 20 years of age at the onset of disease (P < 0.01), while the frequency of HLA-DRB1*15 was significantly decreased in them (P < 0.05), compared with controls. Conclusion, The results suggested that HLA-DRB1 alleles might play an important role in the onset and clinical manifestations of BD. [source] Clinical features of Japanese male patients with type 1 autoimmune hepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006Y. MIYAKE Summary Background Recently, unusual patients with autoimmune hepatitis, such as male patients, have increased. Aim To assess clinical feature of Japanese males with type 1 autoimmune hepatitis compared with females. Methods We investigated consecutive 160 patients with type 1 autoimmune hepatitis, who consisted of 20 males and 140 females, with a median age of 55 (16,79) years. Results Compared with females, males had a lower frequency of definite diagnosis according to the revised scoring system proposed by the International Autoimmune Hepatitis Group (40% vs. 85%) and lower serum levels of immunoglobulin G [1932 (1085,3850) mg/dL vs. 2624 (1354,6562) mg/dL]. However, they were similar in age, form of clinical onset, symptomatic concurrent autoimmune disease, human leucocyte antigen DR status and frequency of cirrhosis at the time of diagnosis. The normalization of serum alanine aminotransferase levels within 6 months after the introduction of corticosteroid treatment was lower in males compared with females (73% vs. 93%). Conclusions In male patients, a diagnosis of autoimmune hepatitis should be made carefully. In Japanese patients with a dominant frequency of human leucocyte antigen DR4, gender may affect the response to corticosteroid treatment. [source] Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006K. HOLM Summary Background The exclusion of oats from the diet in coeliac disease is controversial. Aim To study the long-term safety of oats in the treatment of children with coeliac disease. Methods Altogether 32 children with coeliac disease were enrolled in a 2-year controlled trial. Twenty-three children in remission were randomized either to oats or gluten challenge; when small bowel histological relapse was evident after gluten challenge, a gluten-free diet including oats was started. Furthermore, nine newly detected coeliac patients adopted an oat-containing gluten-free diet. Small bowel mucosal morphology, CD3+, ,,+ and ,,+ intraepithelial lymphocytes, human leucocyte antigen (HLA) DR expression and coeliac serology were determined. After the trial, the children were allowed to eat oats freely; follow-up was extended up to 7 years. Results In coeliac children in remission, oats had no detrimental effect on intestinal histology or serology during the 2-year trial. In contrast, the gluten-challenge group relapsed after 3,12 months. Complete recovery from the disease was accomplished in all relapsed and newly detected patients on an oat-containing gluten-free diet. After the trial, 86% of the children preferred to consume oats and they all remained in remission. Conclusion In most children with coeliac disease, long-term consumption of oats is well tolerated, and it does not result in small bowel mucosal deterioration or immune activation. [source] Review article: Luminex technology for HLA antibody detection in organ transplantationNEPHROLOGY, Issue 2 2009BRIAN D TAIT SUMMARY Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection. [source] Pneumatosis intestinalis in an infant undergoing bone marrow transplantation for Wiskott,Aldrich syndromePEDIATRIC TRANSPLANTATION, Issue 5 2001Duygu Uçkan Abstract: A 7-month-old patient with Wiskott,Aldrich syndrome (WAS) developed pneumatosis intestinalis (PI) in the immediate post-transplant period after receiving paternal human leucocyte antigen (HLA) phenotypically matched bone marrow (BM). PI has been described in patients with congenital or acquired immunodeficiency states and after bone marrow transplantation (BMT). To our knowledge, the condition has not been described in WAS. The underlying bowel mucosa damage as a result of the history of massive rectal bleeding, the effects of the conditioning regimen, immunosuppression, neutropenia, and infection, may all have contributed to the development of PI. Although the condition resolved by conservative management alone, the patient developed Klebsiella pneumonia sepsis, interstitial pneumonitis, failed to engraft, and died on day +66 following a second infusion of stem cells mobilized from his father's peripheral blood. [source] Polyclonal anti-T-cell globulin as part of the preparative regimen for pediatric allogeneic stem-cell transplantationPEDIATRIC TRANSPLANTATION, Issue 4 2001Mats Remberger Abstract: To prevent graft rejection and graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation (ASCT), 56 children were given polyclonal anti-T-cell globulin (ATG) as part of the conditioning regimen. Of the 56 children in the cohort, 27 had a non-malignant disease and 29 had different hematological malignancies. Eight were in first remission of leukemia and the remainder in later stages. Donors were in 16 cases a human leucocyte antigen (HLA)-identical sibling and in 40 a matched unrelated donor (MUD). The control group comprised 16 patients with an HLA-identical donor; the children in this group were not treated with ATG. Side-effects related to the ATG treatment occured in 63% of the patients and included fever, chills, headache, dyspnoea, nausea/vomiting, body pain, fall in blood pressure, and transient respiratory arrest. Engraftment occured in 55 (98%) of the ATG-treated patients at a median of 17 (11,27) days after ASCT. One rejection occured at 23 days post-SCT. The probabilities of acute graft-versus-host disease (GvHD) of grades II,IV were 6% for patients with an HLA-identical donor, 12% for controls, and 26% for the MUD group. Chronic GvHD occured in 20%, 50%, and 50% of patients in the three groups, respectively. Transplant-related mortality rates at 100 days were 6%, 6%, and 7%, respectively. The 5-yr survival rate was 94% and 81% using sibling donors, with and without ATG respectively, and 53% using unrelated donors (p =,0.002). Disregarding donor type, among the ATG-treated patients 5-yr survival rates were 46% in patients with a malignant disease and 77% in non-malignant disorders. Relapse and relapse-free survival rates were 42% and 46%, respectively. Five out of 12 patients who showed an early full donor chimerism in the T-cell lineage developed acute GvHD of grades II,IV, compared to none out of 13 patients being mixed chimeras (p =,0.01). Hence, the use of polyclonal ATG as part of conditioning prior to ASCT in children is safe and the survival rate encouraging. [source] cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA geneANIMAL GENETICS, Issue 2 2001A. Ando cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM , chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes , chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR,restriction fragment length polymorphism (PCR,RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma. [source] Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donorsBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2009Manuel N. Fernández Summary We developed the strategy of umbilical cord blood transplants (UCBT) with co-infusion of a limited number of highly purified mobilized haematopoietic stem cells (MHSC) from a human leucocyte antigen (HLA) unrestricted third party donor (TPD). Short post-transplant periods of neutropenia were usually observed in adults with haematological neoplasms receiving UCBT with a relatively low cell content and 0,3 HLA mismatches after myeloablative conditioning. This resulted from an early and initially predominant engraftment of the TPD,MHSC. After a variable period of double complete TPD + UCB chimerism, final full UCB chimerism was achieved (cumulative incidence >90%) within 100 d. Early recovery of the circulating neutrophils resulting from the ,bridge transplant' of the TPD,MHSC reduced the incidence of serious neutropenia-related infections, also facilitating the use of drugs with myelosuppressive side effects to combat other infections. The observed incidence of graft- versus -host disease and relapses was low, with overall and disease-free survival curves comparable to those of HLA identical sibling transplants. Post-transplant recovery of natural killer cells occurred soon after the transplant and B cells recovered around 6 months, but T-cell recovery took more than 1 year. Available data show that T cell recovery derives from UCB,HSC through thymic differentiation and that cytomegalovirus (CMV)-specific lymphocytes develop following CMV reactivations. [source] | ||||||||||||||||||||||||||||