Dasnayanee Chandanayingyong

Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs), which interact with HLA class I expressed by target cells and consequently regulate cytolytic activity. The number of KIR loci can vary and so a range of genetic profiles is observed. We have determined the KIR genetic profiles from one African (n = 62) and two South Asian (n = 108, n = 78) populations. Several of the KIRs are present at significantly different frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82 African, 0.47 S Asian. Pc < 1 × 10−6) and this is due to uneven distribution of two KIR haplotype families ‘A’ and ‘B’. All three populations described here displayed a greater degree of diversity of KIR genetic profiles than other populations investigated, which indicates further complexity of underlying haplotypes; in this respect we describe two individuals who appear homozygous for a large deletion including the previously ubiquitous 2DL4. We have also reanalysed three populations that we studied previously, for the presence of a KIR which is now known to be an indicator of the ‘B’ haplotype. South Asians had the highest overall frequencies of all KIR loci characteristic of ‘B’ haplotypes (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in the linkage disequilibrium were apparent between populations.

T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221–232 of the DV NS3 protein, in 10 HLA-B*07+ Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF than in those who had experienced DF. We also detected peptide-specific T cells in PBMC obtained at the time of the acute DV infection in 2 of 5 subjects. These data suggest that the NS3 (221–232) epitope is an important target of CD8+ T cells in secondary DV infection and that the activation and expansion of DV-specific T cells is greater in subjects with DHF than in those with dengue fever. These findings support the hypothesis that activation of DV-specific CD8+ T cells plays an important role in the pathogenesis of DHF.

HLA-A, -B, -DRB1, -DQA1, and -DQB1 polymorphism in thais

In this study we examined HLA-A, -B, -DRB1, -DQA1, and -DQB1, gene allele, and haplotype frequencies in two ethnic Thai populations. We compared these frequencies to the known HLA class I and II allele profiles of non-Thai mainland and insular Southeast (SE) Asians. HLA-A locus gene and allele frequencies, are comparatively homogeneous in both Thai and non-Thai SE Asians. In contrast, HLA-B; -DRB1, -DQA1, and -DQB1 gene and allele frequencies, show more ethnic and geographic variation in SE Asians. Conserved haplotypes, or combinations of linked HLA class I and II alleles were detected in Thais, but at relatively low frequencies. It would appear that ethnic Thais, reflect an admixture of peoples from both the northern mainland and southern island groups of SE Asia.

SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex

The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Watterson’s F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wright’s FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them.

Studies on the Miltenberger complex frequency in Thailand and family studies.

Abstract. In studies of Thai blood donors, 243 of 2,500 subjects (9.7%) were Mia positive. All but two were of class Mi III. Family studies established that Mi III is probably inherited as an autosomal dominant character and usually accompanies the Ms gene complex of the MNSs blood group system.

Association of HLA and T-cell receptor gene polymorphisms with semple rabies vaccine-induced autoimmune encephalomyelitis

Semple rabies vaccine is derived from brain tissue infected with rabies virus that is subsequently inactivated with phenol. Semple rabies vaccine–induced autoimmune encephalomyelitis (SAE) occurs in 1 in 220 immunized individuals. The immune response to myelin basic protein and pathological changes of demyelination in SAE suggest that this disease is the human homologue of experimental autoimmune encephalomyelitis (EAE). SAE and EAE are frequently studied as models for the human demyelinating disease multiple sclerosis. Major histocompatibility complex (MHC) class II and T‐cell receptor (TCR) gene polymorphisms play important roles in rodent susceptibility to EAE and were analyzed to determine if the same was true in humans with SAE. HLA‐DRB1, HLA‐DQB1, and TCRBV gene polymorphisms were studied in Thai individuals with SAE (n = 18), with vaccination without neurological complications (n = 43), and without vaccination (n = 140). The allele frequencies of HLA‐DR9 (DRB1*0901) and HLA‐DR17 (DRB1*0301) were increased in SAE patients (DR9 = 22%, DR17 = 14%) compared with vaccinated controls (DR9 = 13%, DR17 = 6%) and with unvaccinated controls (DR9 = 9%, DR17 = 4%). The allele frequency of HLA‐DQ7 (DQB1*0301) was decreased in SAE patients (8%) compared with vaccinated controls (15%) and with unvaccinated controls (25%). These susceptibilities are distinct from those associated with multiple sclerosis. The frequencies of TCRBV alleles and haplotypes were similar in SAE patients and vaccinated controls. These data suggest that genetic susceptibility associated with MHC class II alleles may have a role in the pathogenesis of SAE and its mechanism may be different from those involved in multiple sclerosis. Ann Neurol 1999;45:595–600

The incidence of HLA antigens in leprosy.

Abstract. HLA antigens were studied in 36 patients, with leprosy, 20 cases of lepromatous and 16 cases of tuberculoid type. Eleven out of 36 (30.55%) had BW40 as compared to 9.33% of 150 controls. The frequency of BW40 in tuberculoid patients (31.25%) was not different from that in lepromatous cases (30%).

A comparison of molecular HLA-DR and DQ allele profiles forming DR51-, DR52-, and DR53-related haplotypes in five ethnic Thai populations from Mainland Southeast Asia

Using PCR-SSOP typing we have deduced the composition and frequency of HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, and -DQB1 alleles present in DR51-, DR52-, and DR53-related haplotypes, in 519 individuals representative of five ethnic Thai populations recruited in central, northeastern and northern Thailand. In total, we have unequivocally detected at varying frequencies, 17 DR51-related haplotypes, 24 DR52 haplotypes, and 12 DR53 haplotypes in the study groups. We document evidence of north-south gradients of DR51-related haplotypes, whereby the overall frequency of DR51-containing haplotypes is relatively more common in the northern Thai groups. Similarly, within DR53-related haplotypes the frequency of DRB1*0901-containing haplotypes increases in the more northerly groups, and an inverse effect was observed with DRB1*0701-containing haplotypes that were relatively more common in the northeastern and central Thais. We have also compared the class II haplotype profiles of the Thais with the equivalent profiles reported in other non-Thai ethnic groups from mainland and insular SE Asia. One DR51-related haplotype DRB1*1502x, DRB5*0102x, DQA1*0101/4, DQB1*0501, would appear to be characteristic of Thai populations, as it was the most common DR2 haplotype in all five study groups and is also prevalent in other mainland southeast Asians, but is much less evident in the more northern populations of eastern Asia or China.

Three Antibodies of the MNSs System and Their Association with the Miltenberger Complex of Antigens

Abstract. A new antibody in Anek serum reacts with 7% of Thai Mi III donor samples.

Studies on anti-Mi-a and the MiIII complex.

Abstract. Some Ms/Ms Milll red cells react weakly with rabbit anti‐N but not with human anti‐N sera. Specificities of different anti‐Mia within the Miltenberger complex have been defined by absorbtion studies with different Mi classes.