Showing papers in "Tissue Antigens in 2001"
TL;DR: It is demonstrated that the generation of sHLA-G molecules is associated to certain HLA-G alleles and imply that sHLa-G levels are under genetic control, which suggests different levels of functionality in immune regulation.
Abstract: Soluble HLA-G (sHLA-G) molecules are found in the peripheral blood of healthy females and males, in cord blood and in amniotic fluids and discussed to be a mediator in maternal-fetal tolerance. In this study we investigated whether there are allele-specific differences in expression of sHLA-G molecules. For this, the sHLA-G plasma concentrations of 94 healthy unrelated individuals were measured by ELISA and correlated to their HLA-G genotypes, as determined by sequence analysis of exon 2 and 3 of the HLA-G gene. Mean sHLA-G levels in individuals with the most common HLA-G alleles G*01011 (27.0+/-2.1 SEM ng/ml, n=66), G*01012 (28.4+/-3.2 SEM ng/ml, n=34) were very similar. In contrast, individuals carrying the HLA-G*01013 (8.1+/-1.7 SEM ng/ml, n=17) or the "null" allele HLA-G*0105N (8.2+/-3.2 SEM ng/ml, n=7) presented significantly (P(c)=0.001 and P(c)<0.01, resp.) reduced sHLA-G levels. Furthermore, individuals with the HLA-G*01041 allele had significantly (P(c)=0.004) increased sHLA-G levels (42.5+/-4.6 SEM ng/ml, n=14). These results demonstrate that the generation of sHLA-G molecules is associated to certain HLA-G alleles and imply that sHLA-G levels are under genetic control. As low and high sHLA-G plasma levels did not segregate with HLA haplotypes including the HLA-G*01013 or *01041 allele, additional mechanisms may be involved in the regulation of the individual sHLA-G levels. Nevertheless, the existence of "low" and "high secretor" HLA-G alleles further suggests different levels of functionality in immune regulation.
202 citations
TL;DR: It is demonstrated that different associations and putative KIR haplotypes could be distinguished in different populations, and no correlation was found between the polymorphism of the KIR genes and the HLA specificities of the tested samples.
Abstract: We report the distribution of genes encoding 11 killer cell immunoglobulin-like receptors (KIR) and 2 CD94:NKG2 receptors, in 32 Caucasians, 67 Australian Aborigines and 59 Vietnamese. The inhibitory and the activating KIR genes were found at different frequency in the three populations. No correlation was found between the polymorphism of the KIR genes and the HLA specificities of the tested samples. The most significant KIR associations were 2DL2 with 2DS2; 2DL2 with 2DS3 and 3DL1 with 2DS4 in all three study groups. In Caucasians and Vietnamese 2DS2 was associated with 2DS3 and 2DS1with 3DS1. KIR 2DL1 was strongly associated with three other KIRs: 2DL3, 3DL1 and 2DS4 in Aborigines. The distribution of the KIR phenotypes was different in the three populations. The AA1 phenotype was frequent in Vietnamese (42.4%) and Caucasians (31.2%), but very rare in Aborigines (1.5%). In contrast, the BB7 phenotype was very common for Aborigines (22.4%) and was absent in the two other groups. Our data demonstrate that different associations and putative KIR haplotypes could be distinguished in different populations.
183 citations
TL;DR: Genetic distances are closer between Greeks and Ethiopian/ sub-Saharan groups than to any other Mediterranean group and Greeks cluster with Ethiopians/sub-Saharans in both neighbour joining dendrograms and correspondence analyses.
Abstract: HLA alleles have been determined in individuals from the Republic of Macedonia by DNA typing and sequencing. HLA-A, -B, -DR, -DQ allele frequencies and extended haplotypes have been for the first time determined and the results compared to those of other Mediterraneans, particularly with their neighbouring Greeks. Genetic distances, neighbor-joining dendrograms and correspondence analysis have been performed. The following conclusions have been reached: 1) Macedonians belong to the "older" Mediterranean substratum, like Iberians (including Basques), North Africans, Italians, French, Cretans, Jews, Lebanese, Turks (Anatolians), Armenians and Iranians, 2) Macedonians are not related with geographically close Greeks, who do not belong to the "older" Mediterranenan substratum, 3) Greeks are found to have a substantial relatedness to sub-Saharan (Ethiopian) people, which separate them from other Mediterranean groups. Both Greeks and Ethiopians share quasi-specific DRB1 alleles, such as *0305, *0307, *0411, *0413, *0416, *0417, *0420, *1110, *1112, *1304 and *1310. Genetic distances are closer between Greeks and Ethiopian/sub-Saharan groups than to any other Mediterranean group and finally Greeks cluster with Ethiopians/sub-Saharans in both neighbour joining dendrograms and correspondence analyses. The time period when these relationships might have occurred was ancient but uncertain and might be related to the displacement of Egyptian-Ethiopian people living in pharaonic Egypt.
119 citations
TL;DR: It is concluded that this invasion had a relatively few invaders in comparison to the already settled populations, i.e. Anatolian Hittite and Hurrian groups (older than 2000 B.C.), which may have given rise to present-day Kurdish, Armenian and Turkish populations.
Abstract: Turkish and Kurdish HLA profiles are studied for the first time. The comparative study of their allele frequencies, characteristic haplotypes, genetic distances with other Mediterraneans is complemented by neighbor-joining dendrograms and correspondence analyses. Turks, Kurds, Armenians, Iranians, Jews, Lebanese and other (Eastern and Western) Mediterranean groups seem to share a common ancestry: the older "Mediterranean" substratum. No sign of the postulated Indo-European (Aryan) invasion (1200 B.C.) is detected by our genetic analysis. It is concluded that this invasion, if occurred, had a relatively few invaders in comparison to the already settled populations, i.e. Anatolian Hittite and Hurrian groups (older than 2000 B.C.). These may have given rise to present-day Kurdish, Armenian and Turkish populations.
93 citations
TL;DR: A polymerase chain reaction-sequence-specific primer (PCR-SSP) method which distinguishes all B 27 alleles described at present (B*2701-23) has been developed and two novel B27 alleles were found in this study.
Abstract: A polymerase chain reaction-sequence-specific primer (PCR-SSP) method which distinguishes all B27 alleles described at present (B*2701–23) has been developed. The distribution of B27 alleles was characterised in six different Asian populations. HLA-B*2705, 02, 04, 07, 22 (formerly B*2706) subtypes found in Asian populations differ in their ethnic distribution, which may be the result of different genetic and geographic origins. Furthermore, two novel B27 alleles were found in this study. B*2714 was identified in two Siberians, one of whom was a patient with ankylosing spondylitis. B*2715 was found in two patients with ankylosing spondylitis in Thais. These associations have not previously been reported in either ethnic group.
90 citations
TL;DR: A33-B58-DRB1*03 as discussed by the authors is the most common haplotype among "Taiwanese" with a haplotype frequency of 6.3%, which corresponds to the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese.
Abstract: The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggests that this haplotype is the most well-conserved ancient haplotype of the Yueh.
89 citations
TL;DR: Abundant expression of CD97 was detected on all types of macrophages and dendritic cells, except for microglia, and within the lymphoid lineage, most T cells but only a few B cells express CD97.
Abstract: CD97 is a founding member of the EGF-TM7 family of class II seven-span transmembrane (7-TM) receptors. CD97 has an extended extracellular region with several N-terminal epidermal growth factor (EGF)-like domains, which mediate binding to CD55. Previous studies demonstrated the expression of CD97 on activated lymphocytes, monocytes, macrophages, granulocytes, and numerous haematopoietic and nonhaematopoietic cell lines. Here, we determined the cellular distribution of human CD97 in situ by immunohistochemistry (IH) and immunofluorescence (IF). Abundant expression of CD97 was detected on all types of macrophages and dendritic cells, except for microglia. Within the lymphoid lineage, most T cells but only a few B cells express CD97. Germinal centre B cells do not express the molecule. Except for smooth muscle cells, no staining was found on other cells outside the immune system. However, analysis of a restricted set of epithelial tumors revealed CD97 expression on the malignant cells in thyroid and gastrointestinal tract cancer.
83 citations
TL;DR: Results indicate an association between the presence of G at position -2518 in the MCP-1 promoter region and the Presence of cutaneous vasculitis among patients with SLE.
Abstract: The possible role of the functional polymorphism located in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to systemic lupus erythematosus (SLE) was investigated. Two hundred and seventy-six SLE patients (among them, 99 with lupus nephritis and 55 with cutaneous vasculitis) and 194 ethnically matched healthy controls were included in the study. Genotyping for -2518 (A/G) MCP-1 gene polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No association between -2518 (A/G) MCP-1 polymorphism and susceptibility to SLE nor to lupus nephritis was found. However, a significant increase in the frequency of genotype AG and a decrease in the frequency of genotype AA were found among patients with cutaneous vasculitis (51% of AG vs. 32% in individuals without cutaneous vasculitis; P=0.008, OR=2.2, 95% CI: 1.18-4.25; and 47% of AA vs. 64%; P=0.03, OR=0.5, 95% CI: 0.27-0.96, respectively). These results indicate an association between the presence of G at position -2518 in the MCP-1 promoter region and the presence of cutaneous vasculitis among patients with SLE. This polymorphism does not seem to influence the susceptibility to SLE nor the appearance of lupus nephritis. Further studies are necessary in order to elucidate the role of this polymorphism in the pathogenesis of other inflammatory autoimmune diseases.
78 citations
TL;DR: It is demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years, which is not comparable to the adult immune response.
Abstract: The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically, mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants arid children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM. 1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone, Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response.
75 citations
TL;DR: The data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.
Abstract: In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.
74 citations
TL;DR: A novel approach where amplification of the second exon of HLA-DRB1 is performed in a single tube for all alleles, which results in unambiguous typings in 71.1% of cases.
Abstract: The HLA-DRB1 sequencing based typing strategies reported to date require separate amplifications of each sample with a series of group-specific primers followed by sequencing of any resulting polymerase chain reaction (PCR) products. Whilst this results in high resolution typing in the majority of cases, a number of unnecessary amplifications are performed. We report here a novel approach where amplification of the second exon of HLA-DRB1 is performed in a single tube for all alleles. Retrospective analysis of 642 consecutive Western Australian unrelated bone marrow registry donors has shown that this approach results in unambiguous typings in 71.1% of cases. Ambiguities can be readily resolved if necessary with a single additional sequencing reaction on the original PCR product.
TL;DR: Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region.
Abstract: In order to understand the forces governing the evolution of the genetic diversity in the HLA-DP molecule, polymerase chain reaction (PCR)-based methods were used to characterize genetic variation at the DPA1 and DPB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including individuals of African, Asian, Amerindian, Indian and European origin. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger, presumably admixed populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in significant positive linkage disequilibrium in at least one population. Some haplotypes were found in all ethnic groups while others were confined to a single ethnic group or population. Strong positive global linkage disequilibrium (Wn) between DPA1 and DPB1 was present in all 15 populations. The African populations displayed the lowest values of Wn whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses demonstrate the power of haplotype diversity for inferring the relationships between the different populations.
TL;DR: In this article, the number of KIR genes varies with haplotype and individual genes exhibit polymorphism, and the diversity of human KIR diversity remains to be characterized, particularly in non-Caucasoid populations.
Abstract: :
The killer-cell immunoglobulin-like receptors (KIR) expressed by human natural killer (NK) cells are encoded by a family of genes on chromosome 19. The number of KIR genes varies with haplotype and the individual genes exhibit polymorphism. To investigate KIR diversity we studied KIR cDNA and genes of four human donors: two Caucasians, one Black American and one Asian Indian. From analysis of these donors seventeen novel KIR variants were identified and characterized. Fifteen of the new variants appear to have a simple allelic relationship with a known KIR, whereas two of them combine the sequences of two different KIR genes. Fourteen of the seventeen KIR variants were isolated from the two non-Caucasoid blood donors. These data show that much human KIR diversity remains to be characterized, particularly in non-Caucasoid populations.
TL;DR: Data indicate that multiple mechanisms play a role in the HLA class I antigen-deficient phenotype of human neuroblastoma, and post-transcriptional events were involved in altered TAP-1 and beta2 m expression in one peculiar neuro Blastoma cell line.
Abstract: We studied the constitutive and the interferon (IFN)-gamma-induced expression of HLA class I antigen heavy chain, beta2-microglobulin (beta2m), TAP-1, TAP-2 and tapasin in a panel of eleven neuroblastoma cell lines. Surface expression of HLA class I antigens was low in eight out of eight neuroblastoma cell lines bearing MYC-N amplification and/or 1p deletion, while two out of three neuroblastoma cell lines lacking these genetic alterations showed normal expression. IFN-gamma treatment restored HLA class I antigen surface expression in all neuroblastoma cell lines. Eight out of 11 neuroblastoma cell lines did not express TAP-1 mRNA and three of them also lacked TAP-2 mRNA. beta2 m mRNA was barely detectable or absent in five neuroblastoma cell lines, while tapasin mRNA was always expressed. IFN-gamma upregulated the expression of HLA class I heavy chain, beta2 m, TAP-1, TAP-2 and tapasin, as detected at mRNA or protein level. Post-transcriptional events were involved in altered TAP-1 and beta2 m expression in one peculiar neuroblastoma cell line. These data indicate that multiple mechanisms play a role in the HLA class I antigen-deficient phenotype of human neuroblastoma.
TL;DR: An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed thatDRB1*03 andDRB3*0101 were associated with Löfgren's syndrome in a combined association fashion.
Abstract: Determination of DRB1 and DRB3 specificities in sarcoidosis patients identified that the presence of DRB1*03 and the absence of DRB1*11 and/or DRB1*12 favors a course of disease that is associated positively with Lofgren's syndrome (DRB1*03) and negatively with stage I disease (DRB1*11 and/or 12). In common with normal controls, DRB1*03 was associated with DRB3*0101 and DRB1*11/12 with DRB3*0201/2. An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed that DRB1*03 and DRB3*0101 were associated with Lofgren's syndrome in a combined association fashion. Conversely, a lack of DRB1*11 and/or DRB1*12 but not DRB3*0201/2 favored the clinical course of sarcoidosis.
TL;DR: A segment of 158,063 nucleotides of the pig major histocompatibility complex (SLA) and corresponding to the junction of the class I and class III regions was sequenced entirely and displayed an overall molecular structure compatible with the expression of membrane-anchored glycoproteins.
Abstract: :
A segment of 158,063 nucleotides of the pig major histocompatibility complex (SLA) and corresponding to the junction of the class I and class III regions was sequenced entirely. The centromeric part of the segment contained six class III genes including the three tumor necrosis factor genes, while the telomeric part contained three genes belonging to the class I region. The order and the molecular organization of these genes were exactly conserved in the SLA and HLA complexes, except for the SC1 gene which displayed a shift of the reading frame in swine. The cluster of the three SLA class I-related genes (Ib) and the MIC1 and MIC2 genes were located in the middle of the segment, in the following order from the centromeric side onwards, SLA-6, SLA-7, SLA-8, MIC-1 and MIC-2. All three SLA Ib genes displayed an overall molecular structure compatible with the expression of membrane-anchored glycoproteins. The SLA-7 and SLA-8 genes bear greater resemblance than to the SLA-6 gene. Six SLA-6 alleles have been previously defined differing each from the other by unique point mutations. One of them, appeared to have arisen through the occurrence of a gene conversion event in which the SLA-7 gene served as template. Only MIC-2 gene might be functional, the second MIC-1 gene being truncated. In all, the 14 genes characterized spans 37% of the total sequence. The remaining 63% nucleotides comprised a number of repeat DNA motives, including LINE fragments, SINEs, microsatellites, and also numerous nucleotide stretches not yet defined in swine.
TL;DR: Investigation of the genetic diversity of HLA-A*02 in the North Indian population revealed a high occurrence of A*0211 in this population along with increased frequencies of the common Oriental alleles and an unexpectedly low frequency of A-0201 in contrast to its distribution in Western Caucasians in whom it constitutes 95% of the Hla-A2 repertoire.
Abstract: The North Indians are considered predominantly Caucasoid with an admixture of genes from the Mongoloid and Aryan races. The present study was undertaken to investigate the genetic diversity of HLA-A*02 in the North Indian population and determine the frequency distribution of its molecular subtypes at the population level. The study revealed a high occurrence of A*0211 (33.8%) in this population along with increased frequencies of the common Oriental alleles, A*0206 (7.5%) and A*0207 (32.5%) and also of HLA-A*0205 (15%) commonly observed in negroid populations. HLA-A*0211 has only been reported with very low frequencies among the Ticuna Jews, Thai population, and Colombian Blacks in the malaria endemic areas of Africa. Significantly, we observed an unexpectedly low frequency of A*0201 (3.8%) in contrast to its distribution in Western Caucasians in whom it constitutes 95% of the HLA-A2 repertoire. Prevalence of HLA-A*0211 at very high frequencies among North Indians may be a consequence of the founder effect, racial admixture or selection pressure due to environmental factors in this population.
TL;DR: In this paper, the constitutive and cytokine-regulated expression pattern of tapasin in malignant cells of distinct histology was found in small-cell lung carcinoma, pancreatic cancer, colon cancer, head an neck squamous cell carcinoma and renal cell cancer cell lines.
Abstract: Human tumor cells frequently exhibit abnormalities in the major histocompatibility complex (MHC) class I surface expression which can be due to structural alterations and/or dysregulation of various components of the MHC class I antigen processing machinery, such as HLA class I heavy and light chains, the peptide transporter and the proteasome subunits. Although several cofactors critical for proper MHC class I assembly have been identified, their contribution to the immune escape phenotype of tumor cells has not been analyzed. In order to determine whether tapasin deficits are an integral part of immune escape mechanisms of human tumors, we studied the constitutive and cytokine-regulated expression pattern of tapasin in malignant cells of distinct histology. Heterogeneous and reduced expression levels of tapasin were found in small-cell lung carcinoma, pancreatic carcinoma, colon carcinoma, head an neck squamous cell carcinoma and renal cell carcinoma cell lines. Tapasin downregulation was also prominent in surgically removed tumor lesions when compared to normal controls. The impaired tapasin expression is often associated with low MHC class I cell surface expression. In addition, various cytokines, including interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, but not granulocyte-macrophage colony stimulating factor (GM-CSF), transcriptionally upregulate to a distinct extent and in a time-dependent manner tapasin expression in tumor cells. Thus, deficient tapasin expression appears to be a frequent event in human tumor cells. Its restoration by cytokines further suggests that impaired tapasin expression in tumors is rather due to dysregulation than to structural alterations.
TL;DR: The distribution of DQ genes in the Saharawi population only provides a partial explanation for the high prevalence of CD, and other factors, such as rapidly changing dietary habits and/or non-DQ genes, may also play some role.
Abstract: Celiac disease (CD) is a multifactorial disorder of the small intestine caused by a permanent dietary intolerance to gluten. The combined presence of the HLA class II DQA1 * 0501 and DQB1 * 0201 alleles represents the majorgenetic component for disease predisposition. It has been shown that the Saharawi refugees living in northern Africa have a very high frequency of CD. In the present study we analysed this population to evaluate the degree of association with CD of the haplotypes and genotypes at the main HLA-DQB1 and DQA1 disease loci. We found a strong association of the DR3, DQB1*0201-DQA1*0501-positive haplotypes and genotypes. A very high frequency of DR3, DQB1 * 0201-DQA1 * 0501 was also observed in the general Saharawi population. These results indicate that there is a good correlation between disease prevalence and frequency of the main predisposing haplotype in the background population. However, the correlation is incomplete because similar frequencies of DR3 are also observed in populations such as the Sardinians showing a much lower prevalence of CD. We can conclude that the distribution of DQ genes in the Saharawi population only provides a partial explanation for the high prevalence of CD. Other factors, such as rapidly changing dietary habits and/or non-DQ genes, may also play some role.
TL;DR: It is found that Taiwan's indigenous tribes are more or less genetically related to both northern and southern Asians, possibly as well as Amerindians, and also to Oceania, Australian aborigines, south and north east Asians and American Indians.
Abstract: Taiwan's indigenous tribes, especially the east coast tribes are not only closely related to Oceania but also with the Australian aborigines The Ivatans of the Batan Islands in the Philippines are closely related to the Yami tribe of Taiwan as cultural and anthropological studies have shown Many DRB1 alleles (*15021, *16021, *0404, *04051, *11011, *12021, *1401, *08032) have high allele frequencies (20%) in certain tribes, suggesting Taiwan's in- digenous tribes are homogeneous populations These high frequency DRB1 alleles and also some HLA-A-B-DR haplotypes found in Taiwan's indigenous tribes are also found in Oceania, Australian aborigines, south and north east Asians and American Indians, lending further support to our previous findings that Taiwan's indigenous tribes are more or less genetically related to both northern and southern Asians, possibly as well as Amerindians HLA-A*2402 with a remarkably high frequency among Taiwan's indigenous tribes (521%¶863%), especially the central mountain tribes, possibly represents not only founder effects and population bottlenecks, but also positive selec- tion of the allele Although the Ami tribe has the highest ever reported frequen- cies of the DRB1*0404 and DRB1*0405, these alleles have not been found to be associated with rheumatoid arthritis as previously described for Caucasi- ans In addition, DRB1*1401 has a high frequency in most tribes but is not associated with psoriasis as previously indicated in some studies, suggesting the involvement of some additional genetic and/or environmental factors mechanism in the development of these diseases Taiwan's indigenous peoples although comprising only 15% of Tai- wan's total population are homogeneous within each tribe but sig- nificantly different between tribes, yet have affinities to make a clus- ter together in the population dendrogram as reported in our pre- vious HLA class I study (1) Many of the HLA class I haplotypes found in Taiwan's indigenous tribes are observed not only in Oceania (PNG Highlanders, Maori) but also in northern Asians (In- uit, Orochons, Mongolians, Japanese, Man and Buryat) and North Amerindians (Tlingit), suggesting Taiwan's indigenous tribes are more or less genetically related to both northern and southern Asi- ans, and supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place Authors' affiliations: 2 , 4
TL;DR: This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the SOTA-B*5101 allele.
Abstract: Behcet’s disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA-B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101–B*5121. Further, not only HLA-B*5101 but also HLA-B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. Ninety-six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; Pc=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51-positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51-positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA-B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA-B*5101 allele.
TL;DR: In this article, the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria.
Abstract: To investigate the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria. Two hundred and forty-three Myanmar patients with falciparum malaria at Mae Sot Malaria clinic and Mae Sot General Hospital located at the border between Thailand and Myanmar, were included in this study. Among the patients (128 from Karen, 115 from Burma), 200 were uncomplicated and 43 had cerebral malaria. The TNF-alpha 5'- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles (TNFP-A, B, C, D, M1, M4, M7) found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc<0.0001, OR=124.86) and Burma (Pc<0.0001, OR=34.50). TNFP-D showed no significant linkage disequilibrium with any alleles of HLA-B or HLA-DRB1, suggesting that TNFP-D was primarily associated with cerebral malaria in Myanmar.
TL;DR: It is suggested that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.
Abstract: RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P<0.01) with the frequency of those in AA genotype being elevated (P<0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was significantly increased (P<0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.
TL;DR: It is suggested that the HLA DR/DQ haplotype/genotype frequencies observed could in part explain the low incidence of type 1 diabetes registered in Lazio region.
Abstract: HLA class II is the primary susceptibility gene to type 1 diabetes and the analysis of HLA class II association could help to clarify the relative weight of genetic contribution to the incidence of the disease. Here we present an extensive typing for HLA class II alleles and their haplotypes in a homogenous population of type 1 diabetic patients (n=134) and controls (n=128) and in simplex (n=100) and multiplex families (n=50) from continental Italy (Lazio region). Among the various haplotypes tested, the DRB1 * 0301-DQA1 * 0501-DQB1 * 0201 was the most frequent found in type 1 diabetic patients and was transmitted in 82% of affected siblings, whereas DRB1 * 0402-DQA1 * 0301-DQB1 * 0302 appeared to have the highest odds ratio (10.4), this haplotype was transmitted in 96.3% of affected siblings, followed by DRB1 * 0405-DQA1 * 0301-DQB1 * 0302, DRB1 * 0405-DQA1 * 0301-DQB1 * 0201, DRB1 * 0401-DQA1 * 0301-DQB1 * 0302 and DRB1 * 0404-DQA1 * 0301-DQB1 * 0302. The following haplotypes showed a significant decreased transmission to diabetic siblings: DRB1 * 0701-DQA1 * 0201-DQB1 * 0303, DR2-DQA1 * 01-DQB1 * 0602, DR5-DQA1 * 0501-DQB1 * 0301. We suggest that the HLA DR/DQ haplotype/genotype frequencies observed could in part explain the low incidence of type 1 diabetes registered in Lazio region (8.1/100.000/year), for a number of reasons: i) the low frequency, in the general control population, of the most susceptible haplotypes and genotype for type 1 diabetes DRB1 * 0301-DQA1 * 0501-DQB1 * 0201 (14%), and DR4-DQA1 * 0301-DQB1 * 0302 (9%) and DRB1 * 0301-DQA1 * 0501-DQB1 * 0201/DR4-DQA1 * 0301-DQB1 * 0302 (0.8%) compared to other countries characterised by high incidence rate of the disease, Sardinia and Finland, respectively; ii) a significant lower ratio, in the control population, between the susceptible DRB1 * 0301-DQA1 * 0501-DQB1 * 0201 and the neutral DRB1 * 0701--DQA1 * 0501-DQB1 * 0201 haplotypes compared to the Sardinian population; iii) the high frequency of protection haplotypes/genotypes as the DR5-DQA1 * 0501-DQB1 * 0301, and DR5-DQA1 * 0501-DQB1 * 0301/DR5-DQA1 * 0501-DQB1 * 0301 very common in the control population of Lazio region and the DRB1 * 1401-DQA1 * 0101-DQB1 * 0503 haplotype.
TL;DR: This study does not suggest the involvement of HLA I in the higher resistance to malaria of Fulani, and confirms a low, if any, Caucasoid component in their gene pool.
Abstract: Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibe. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibe and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibe data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001
University of Minnesota1, American Red Cross2, National Marrow Donor Program3, University of Maryland, College Park4, University of Pennsylvania5, University of California, Los Angeles6, Children's Hospital of Philadelphia7, Memorial Hospital of South Bend8, Fred Hutchinson Cancer Research Center9, Memorial Sloan Kettering Cancer Center10, Georgetown University Medical Center11
TL;DR: DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at H LA-B, and more than 97% at both HLA -A and -B validating this methodology for registry typing.
Abstract: A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and PCR-based typing. The HLA assignments included all of the known serological equivalents. The majority of the individuals (99.9%) were from U.S. minority population groups. The serologic typing was performed between 1993 and 1997 at the time of recruitment for the National Bone Marrow Program (NMDP) registry. The polymerase chain reaction (PCR)-based typing was carried out in two phases. In phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without knowledge of the serologic assignments. Discrepancies were identified between the serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a potential explanation was assigned each discrepant serology/DNA pair. In phase II, a random sampling scheme was used to select a statistically significant number of individuals for repeat DNA typing from each of these categories. The categories included antigens missed by serology, nonexpressed (null) alleles, PCR amplification failures, misassignment of antigens and nomenclature issues. Only a single individual was found to carry a null allele. DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than 97% at both HLA-A and -B validating this methodology for registry typing.
TL;DR: No associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis are found and it is unlikely that the Mica and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.
Abstract: MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by gammadelta T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA-B and TNFalpha. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA-B gene, in patients of Caucasoid origin with Crohn's disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis. We could also not discover any associations of specific two-point or three-point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.
TL;DR: It is reported here that a cytolytic T-lymphocyte (CTL) clone, which is restricted by HLA-B*3501, recognizes the same peptide and, importantly, lyses HLA_B* 3501 tumor cells expressing MAGE-3, infer that the current clinical use of peptide EVDPIGHLY can now be extended to HLA*35 01 patients.
Abstract: Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Antigenic peptide EVDPIGHLY encoded by MAGE-3 and known to be presented by HLA-A*0101 is currently being used in therapeutic vaccination trials. We report here that a cytolytic T-lymphocyte (CTL) clone, which is restricted by HLA-B*3501, recognizes the same peptide and, importantly, lyses HLA-B*3501 tumor cells expressing MAGE-3. These results infer that the current clinical use of peptide EVDPIGHLY can now be extended to HLA-B*3501 patients.
TL;DR: This study systematically investigated the accuracy of HLA class I serological AB typing in healthy, bone-marrow registry donors, necrokidney donors, kidney-transplantation patients (on waiting lists), and haematological disorder patients, and recommended that patients with haem atological disorders should be typed using genomic techniques.
Abstract: Until recently, serological typing has been the primary technique used for HLA class I analysis. But because of limitations, molecular-typing techniques have replaced or supplemented the microlymphocytotoxicity test. It has been assumed that HLA class I serological typing was more accurate than serological HLA-DR typing; the latter has been shown to have 10-25% errors. But several studies have shown that HLA-AB typing was poorer than expected, and error frequencies between 5-25% were reported. This study systematically investigated the accuracy of HLA class I serological AB typing in healthy, bone-marrow registry donors, necrokidney donors, kidney-transplantation patients (on waiting lists), and haematological disorder patients. Genomic HLA class I typing, which uses polymerase-chain reaction with sequence-specific primers (PCR-SSP), gave discrepant results in 3-24% of the patients, compared to serological typings. The highest error rate (24%) was found among haematological disorder patients. Among the kidney waiting-list patients and necrokidney donors, 11% discrepancies were found. In the consecutively typed bone-marrow donors group, 3% errors were found. But among those with only one detected HLA-A specificity, 12% discrepancies were found, and among donors with only one detected HLA-B specificity, 19% errors were found. Based on these results, we recommend that patients with haematological disorders should be typed using genomic techniques. In investigations of bone-marrow registry donors and kidney patients, in which only one serological specificity is found, additional typing by genomic methods should be done.
TL;DR: The findings suggest that the novel promoter polymorphism of the NRAMP1 gene may influence susceptibility to IBD in the Japanese population.
Abstract: Inflammatory bowel diseases (IBD) representing both Crohn's disease and ulcerative colitis are characterized by chronic activation of macrophages. Natural resistance-associated macrophage protein 1 (NRAMP1) gene regulates macrophage activation of antimicrobial activity and has many pleiotropic effects on macrophage functions. To explore the role of the NRAMP1 gene in IBD susceptibility, we examined the promoter sequence of the NRAMP1 gene whose polymorphisms have been reported to influence the transcriptional activity of the NRAMP1 gene. One novel allele (allele 7) and two previously reported alleles (alleles 2 and 3) have been determined in a Japanese population. We investigated the association of IBD with these three alleles. The allele frequency of allele 7 was significantly higher in patients with Crohn's disease (11.1%) and ulcerative colitis (11.2%) than those in the healthy control group (4.5%) (Pc=0.015, Pc=0.018, respectively). Therefore, our findings suggest that the novel promoter polymorphism of the NRAMP1 gene may influence susceptibility to IBD in the Japanese population.