This study demonstrates not only the differential association between HLA markers and types of psoriasis according to age at onset, but also a newly found high-risk and a protective haplotype in Thai psoriasis patients.
MICA or PERB11.1 is a polymorphic major histocompatibility complex (MHC) class I-related gene located 46 kb centromeric of the HLA-B gene in the HLA class I region. It is expressed mainly in gut epithelial cells, keratinocytes, endothelial cells, fibroblasts and monocytes, and is upregulated by heat stress. MICA has been found to interact with gamma delta T cells, alpha beta CD8(+) and natural killer (NK) cells bearing the NKG2D/DAP10 receptor. The MICA gene displays a high degree of polymorphism with at least 54 alleles. In the present study, polymorphic exons 2, 3 and 4 of the MICA gene were analyzed using sequencing based typing (SBT) in 255 unrelated healthy northeastern Thais. Thirteen previously reported MICA alleles were detected. MICA*008, *010, *002 and *019 were highly predominant with the allele frequencies of 21.4%, 18.2%, 17.6% and 15.3%, respectively. Five of these 13 MICA alleles show significantly different frequencies from those of the Japanese and Caucasian populations. Interestingly, MICA052, which is a very rare allele in other populations, was prevalent with the allele frequency of 8.2%, mainly on the HLA haplotype carrying HLA-B*13 in this population. Strong linkage disequilibria were observed between MICA and HLA-B, as similarly observed in other populations, namely MICA*010-B*4601, MICA052-B*13, MICA*002-B*5801, and MICA*019-B*15 (1502, 1508, 1511, 1515, 1528, 1530). A large variety of three-locus (MICA - HLA-B - HLA-Cw) and six-locus (HLA-DQB1 - HLA-DRB1 - MICA - HLA-B - HLA-Cw - HLA-A) haplotypes were recognized in the northeastern Thai population. This is the first report on MICA allelic distribution in Southeast Asian populations. These data will provide the important basis for future analyses on the potential role of the MICA gene in disease susceptibility and transplantation matching in Southeast Asian populations.
Unique long 16 (UL-16)-binding proteins (ULBP) or retinoic acid early transcripts-1 (RAET1) are ligands to the activating receptor, NKG2D. The human RAET1/ULBP gene family is identified as ten members (RAET1E to N) with six loci encoding for potentially functional proteins. These are ULBP1 or RAET1I, ULBP2 or RAET1H, ULBP3 or RAET1N, and RAET1L, which are glycosylinositol phospholipid (GPI)-linked glycoproteins and ULBP4 or RAET1E and ULBP5 or RAET1G, which are transmembrane glycoproteins. The RAET1 products contain the alpha1 and alpha2 domains but lack the alpha3 domain and do not associate with beta2-microglobulin. RAET1/ULBPs have tissue-specific expressions, and some of them are also polymorphic. In the present study, polymorphic exons 2 and 3 of the RAET1E, G, H, I, L, and N were analyzed using sequence-based typing. One hundred and seventy-six unrelated healthy Northeastern Thais were included in this study. For RAET1E, RAET1G, RAET1H, and RAET1L, there were seven, two, five, and four single nucleotide polymorphisms (SNPs), respectively. Six of these are new SNPs, which are rare in this population. Of these, six new SNPs, two of two in RAET1E, two of three in RAET1H, and none of one in RAET1L are nonsynonymous substitutions. Interestingly, although the RAET1N is polymorphic in Caucasians, RAET1N and RAET1I had no variation in Thais indicating diverse RAET1 genes in different ethnic groups. These data provide the important basis for future analysis on the role of RAET1 genes in immune responses especially in cancer and infectious diseases.
HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype other than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.
The prevalence, alloimmunization risk factors, antigenic exposure, and evaluation of antigen-matched red blood cells for thalassemia transfusions: a 10-year experience at a tertiary care hospital BACKGROUND: Hemoglobin E-β 0 thalassemia and homozygous β 0 -thalassemia are the most common chronic transfusion-dependent thalassemias in Thailand. Patients with these conditions can experience clinical complications such as RBC alloimmunization. In this study we aimed to determine the prevalence, alloimmunization risk factors, antigenic exposure, and evaluation of antigen-(C, c, E, e, Mi a ) matched RBC transfusion. STUDY DESIGN AND METHODS: Thalassemia patients were recruited from a tertiary care hospital for 10 years from 2008 to 2017. The medical records of transfusion history were reviewed for red cell phenotype both of patients and donors, number of units transfused, and type of alloantibodies. RESULTS: A total of 383 thalassemia patients were identified (178 males and 205 females). The frequency of RBC alloantibodies was 19.3%. Some patients tested positive for more than one antibody type. Autoantibodies were detected in nine individuals. Anti-E (49 [39.5%]), anti-Mi a (24 [19.4%]), and anti-c (19 [15.3%]) were the most common antibodies detected. A high rate of alloimmunization was found in splenectomized patients. Risk of alloimmunization increased when more total units of blood had been transfused. A trend toward low alloimmunization rates was noted in the antigen-matched RBC group, where 3.5% (5/143) of patients were alloimmunized. Anti-E and anti-Mi a , which may be naturally occurring, were identified in this group.CONCLUSION: Thai patients are more prone to develop antibodies against the Rh and Mi a than to the Kell blood group antigens.
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