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In Chan Baek,1 Kyungeun Park,1 Tae Lim Kim,1 Jehoon O,2 Hun-Mu Yang,2,* Shin Hyung Kim1,* 1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work. Purpose: The spread patterns between different injectate volumes have not yet been investigated in ultrasound-guided greater occipital nerve (GON) block at the C2 level. This cadaveric study was undertaken to compare the spread pattern and nerve involvements of different volumes of dye using this technique. Materials and methods: After randomization, ultrasound-guided GON blocks with 1 or 5 mL dye solution were performed at the C2 level on the right or left side of five fresh cadavers. The suboccipital regions were dissected, and nerve involvement was investigated. Results: Ten injections were successfully completed. In all cases of 5 mL dye, we observed the deeply stained posterior neck muscles, including the suboccipital triangle space. The suboccipital and third occipital nerves, in addition to GONs, were consistently stained when 5-mL dye was used in all injections (100%). Although all GONs were successfully stained in the 1-mL dye cases, three of five injections (60%) concomitantly stained the third occipital nerves. Conclusion: The clinical efficacy of this technique using the 5-mL injectate seems unlikely to arise from the blockade of GON alone. Instead, its efficacy likely arises from the blockade of most nerves originating from the dorsal ramus of the upper cervical spinal nerve at the suboccipital area. Even using 1 mL of injectate may not guarantee blockade of the GON alone. Keywords: obliquus capitis inferior, third occipital nerve, suboccipital nerve, Cruveilhier plexus, suboccipital triangle region, headache

Background: The reactivation and loss of mosaicism hypothesis due to X chromosome inactivation (XCI) skewing and escape could influence gender differences in autoimmune diseases. XCI selectively inactivates one of the two X chromosomes in females., Methods: To estimate XCI skewing and the occurrence of XCI escape, we conducted a normal female (NF) without a history of autoimmune thyroid disease (AITD) and a patient with Grave's disease (GD) based on a thyroid diagnosis. After single-cell RNA sequencing, heterozygous variants were converted and transformed. XCI skewing was calculated using the formula and the skewing degree was defined. NF/GD genes were compared using correction methods. Positions are heterozygous within a single cell as indicated by a unique barcode., Results: XCI skewing showed 45.8%/48.9% relatively random, 29.4%/27.0% skewing, 24.6%/23.7% severe skewing, and 0.2%/0.4% extreme severe skewing. 24.8%/24.1% in NF/GD exhibited severe skewing or higher. A total of 13 genes were significantly associated with XCI skewing ratios in NF/GD cells. In total, 371/250 nucleotide positions with only one barcode (representing a unique cell) were identified for XCI escape. A total of 143/52 nucleotide positions spanned 20/6 genes, and 12/1 genes were identified as XCI escapes., Conclusions: These results could aid in understanding the immunogenetics of gender differences in various autoimmune disease pathophysiologies., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided informed consent for this genetic study. This study was approved by the Institutional Review Board (IRB) of The Catholic University of Korea (IRB Number: VC17TESI0129), Seoul, Korea, and the study was conducted in accordance with the Declaration of Helsinki. Consent for publication: The authors have nothing to disclose. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Turner syndrome (TS) can be determined by karyotype analysis, marked by the loss of one X chromosome in females. However, the genes involved in autoimmunity in TS patients remain unclear. In this study, we aimed to analyze differences in immune gene expression between a patient with TS, a healthy female, and a female patient with Graves' disease using single-cell RNA sequencing (scRNA-seq) analysis of antigen-specific CD4(+) T cells. We identified 43 differentially expressed genes in the TS patient compared with the healthy female and the female patient with Graves' disease. Many of these genes have previously been suggested to play a role in immune system regulation. This study provides valuable insights into the differences in immune-related gene expression between TS patients, healthy individuals, and those with autoimmune diseases.

Human leukocyte antigen (HLA) is a group of glycoproteins encoded by the major histocompatibility complex (MHC) that plays a pivotal role in the host's immune defense. Given that the MHC represents the most polymorphic region in the human genome, HLA typing is crucial in organ transplantation. It significantly influences graft rejection, graft-versus-host disease, and the overall patient outcome by mediating the discrimination between self and nonself. HLA typing technology began with serological methods and has evolved rapidly alongside advances in molecular technologies, progressing from DNA-based typing to next- or third-generation sequencing. These advancements have increased the accuracy of HLA typing and reduced ambiguities, leading to marked improvements in transplantation outcomes. Additionally, numerous novel HLA alleles have been identified. In this review, we explore the developmental history and future prospects of HLA typing technology, which promises to further benefit the field of transplantation.

HLA-B*27:264 differs from HLA-B*27:05:02:01 in codon 49 in exon 2., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*31:217 differs from HLA-A*31:01:02:01 in codon 37 in exon 2., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Major histocompatibility complex class I chain-related genes A and B (MICA and MICB) play a role as ligands in activating the NKG2D receptor expressed in natural killer cells, γδ T-cells and αβ CD8 T-cells and have been defined in human diseases and haematopoietic stem cell transplantation (HSCT). MICA and MICB alleles were genotyped at the three-field level by amplicon-based next-generation sequencing (NGS) using a MiSeqDx system and compared with the results from previous studies in healthy South Korean donors. Exons 2-5 of MICA and exons 2-4 of MICB were amplified using a multiplex polymerase chain reaction (PCR). Sequence reads of ≥ 51 depth counts were consistently obtained for each sample exon, and target exons were determined to match reference sequences contained in the IPD-IMGT/HLA database. MICA and MICB alleles were tested using exon combinations. The program was designed to recognise specific sequences and discriminate between the MICA*008:01:01/*027 alleles. A total of 22 alleles were found in MICA and MICB. We observed 1 HLA-C ~ HLA-B ~ MICA ~ MICB ~ HLA-DRB1 haplotype with significant linkage disequilibrium between alleles at all neighbouring HLA loci. These results are consistent with previous microarray results. Genotyping of MICA and MICB was possible using 11-loci HLA genes. We updated the distribution of MICA and MICB based on three-field allele and haplotype frequencies containing linkage disequilibrium in South Koreans using amplicon-based NGS. These data suggest that high-resolution MICA and MICB typing data obtained using NGS may aid in performing HSCT and disease association studies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans., Methods: KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes., Results: KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group ( p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases., Conclusion: Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

Killer-cell immunoglobulin-like receptors (KIR) control natural killer (NK) cell functions by recognizing HLA molecules and modulating the activity of NK cells. The KIR gene cluster contains polymorphic and highly homologous genes. Diversity of the KIR region is achieved through differences in gene content, allelic polymorphism, and gene copy number, which result in unrelated individuals having different KIR genotypes and individualized immune responses that are relevant to multiple aspects of human health and disease. Therefore, KIR genotyping is increasingly used in epidemiological studies. Here, we developed multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP) to compensate for the shortcomings of the conventional PCR-SSP method, which is most commonly used for KIR analysis. Multiplex PCR-SSP method involves six multiplex reactions that detect 16 KIR genes and distinguish variant types of some KIR genes by adding two reactions. The assay was evaluated in a blind survey using a panel of 40 reference DNA standards from the UCLA KIR Exchange Program. The results are 100% concordant with the genotype determined using Luminex-based reverse sequence-specific oligonucleotide typing systems. Additionally, we investigated the currently known 16 KIR genes and their common variants in 120 unrelated Korean individuals. The results were consistent with the KIR genotype previously reported by Hwang et al. This multiplex PCR-SSP is an efficient method for analyzing KIR genotypes in both small- and large-scale studies with minimal labor, reagents, and DNA. Furthermore, by providing a better definition of KIR polymorphisms it can contribute to developments in immunogenetics., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chemokines are chemotactic cytokines that can cause directed migration of leukocytes. The aim of this study was to examine differences in single nucleotide polymorphisms (SNP) of chemokine in AITD patients compared to normal controls. A total of 86 Korean pediatric patients were included in the patient group and 183 adults were included in the normal control group. To compare influences of several chemokine gene polymorphisms, 25 SNPs in 16 chemokine genes were analyzed. Genotype frequencies of CCL11(rs3744508)AA(OR = 6.9) and CCR2(rs1799864)AA(OR = 3.8) were higher in the AITD patients than in the controls, whereas CCL17(rs223828)CC was lower in the AITD patients than in the controls(OR = 0.4). In comparison between Graves' disease (GD) patients and controls, genotype frequency of CCL17(rs223828)CC(OR = 0.4) was lower in the GD group, whereas those of CCR2(rs1799864)AA(OR = 4.8) were higher in the GD group. The genotype frequency of CCL11(rs3744508)AA(OR = 11.3) was higher in Hashimoto's thyroiditis (HT) patients, whereas that of CXCL8(rs2227306)CC(OR = 0.4) was lower in HT patients. Polymorphisms of CCL11(rs3744508), CCL17(rs223828), and CCR2(rs1799864) might be associated with AITD, with CCL17(rs223828), CCR2(rs1799864) and CXCR2(rs2230054, rs1126579) affecting GD and CCL11(rs3744508) and CXCL8(rs2227306) affecting HT in Korean children., (© 2023. Springer Nature Limited.)

Purpose: The immune responses of natural killer (NK) cells against cancer cells vary by patient. Killer Ig-like receptors (KIRs), which are some of the major receptors involved in regulating NK cell activity for killing cancer cells, have significant genetic variation. Numerous studies have suggested a potential association between the genetic variation of KIR genes and the risk of development or prognosis of various cancer types. However, an association between genetic variations of KIR genes and glioblastoma (GB) remains uncertain. We sought to evaluate the association of genetic variations of KIRs and their ligand genes with the risk of GB development in Koreans., Methods: A case-control study was performed to identify the odds ratios (ORs) of KIR genes and Classes A, B, and, C of the human leukocyte antigen (HLA) for GB. The GB group was comprised of 77 patients with newly diagnosed IDH-wildtype GB at our institution, and the control group consisted of 200 healthy Korean volunteers., Results: There was no significant difference in the frequency of KIR genes and KIR haplotypes between the GB and control groups. Genetic variations of KIR-2DL1, 3DL1, and 3DS1 with their ligand genes (HLA-C2, HLA-Bw4/6, and Bw4, respectively) had effects on the risk of GB in Korean patients. The frequency of KIR-2DL1 with HLA-C2 (OR 2.05, CI 1.19-3.52, p = 0.009), the frequency of KIR-3DL1 without HLA-Bw4 (80I) (OR 8.36, CI 4.06-17.18, p < 0.001), and the frequency of KIR-3DL1 with Bw6 (OR 4.54, CI 2.55-8.09, p < 0.001) in the GB group were higher than in the control group. In addition, the frequency of KIR-2DL1 without HLA-C2 (OR 0.44, CI 0.26-0.75, p = 0.003), the frequency of KIR-3DL1 with HLA-Bw4 (80T) (OR 0.13, CI 0.06-0.27, p < 0.001), the frequency of KIR-3DL1 without Bw6 (OR 0.27, CI 0.15-0.49, p < 0.001), and the frequency of KIR-3DS1 with Bw4 (80I) (OR 0.03, CI 0.00-0.50, p < 0.001) in the GB group were lower than in the control group., Conclusions: This study suggests that genetic variations of KIRs and their ligand genes may affect GB development in the Korean population. Further investigations are needed to demonstrate the different immune responses for GB cells according to genetic variations of KIR genes and their ligand genes.

The range of HLA typing for successful hematopoietic stem cell transplantation (HSCT) is gradually expanding with the next-generation sequencing (NGS)-based improvement in its quality. However, it is influenced by the allocation of finances and laboratory conditions. HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 alleles were genotyped at the 3-field level by amplicon-based NGS using MiSeqDx system and compared to our previous study employing long-range PCR and NGS using TruSight HLA v2 kit, in healthy donors from South Korea. Exon 2, exons 2/3, exons 2/3/4 or 5 of 11-loci were amplified by multiplex PCR. The sequence reads of over 53 depth counts were consistently obtained in each sample exon, depending on the target exon determined to match the reference sequence contained in the IPD-IMGT/HLA Database. HLA alleles were investigated by combinations of the determined exons. A total of 18 alleles with a frequency over 10% were found at the 11 HLA loci. Three ambiguities of HLA-A, -C, and -DRB1 were resolved. We observed a total of 26 HLA-A ~ C ~ B and 6 HLA-DRB1 ~ DQA1 ~ DQB1 ~ DPA1 ~ DPB1 haplotypes having significant linkage disequilibrium between alleles at all neighboring HLA loci. This result was compatible with the previous one, using TruSight HLA v2 kit. Advantages are simple and short progress time because one plate is used for each PCR step in one PCR machine and 11-loci HLA typing is possible even if only eight samples. These data suggested that expanded 11-loci HLA typing data by amplicon-based NGS might help perform HSCT., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Autoimmune thyroid disease (AITD) manifests with a female predominance, and much attention has been directed towards the integral membrane protein 2 A (ITM2A) gene located on the X chromosome., Methods: In a study of 166 pediatric patients with autoimmune thyroid disease (AITD), the ITM2A rs1751094 single-nucleotide polymorphism (SNP) was genotyped. The sample comprised 143 females and 23 males, with 67 patients diagnosed with Hashimoto chronic thyroiditis (HD) and 99 with Graves' disease (GD). In the 99 GD patients, 49 (49.5%) exhibited thyroid-associated ophthalmopathy (TAO). Among the 85 GD patients, 70.6% (60/85) were considered intractable GD. The results were compared to those from 198 healthy Korean individuals, including 97 females and 101 males., Results: The frequency of the rs1751094 C allele and CC/AC genotype were higher in AITD, GD and HD patients compared to controls, while the frequency of the A allele and AA genotype were lower. The results were more pronounced in female AITD and GD patients compared to male patients. The association was also found in intractable GD and TAO patients. Target SNP fits Hardy-Weinberg equilibrium., Conclusions: These findings indicate that the ITM2A gene polymorphism on the X chromosome may contribute to the immunological basis of female-predominant AITD in Korean children., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8 + and CD4 + T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8 + T cell responses were significantly higher than CD4 + T cell responses. CD8 + T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4 + T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×10 5 CD8 + or CD4 + T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

Advances in next-generation sequencing (NGS) have improved the resolution of T-cell receptor (TCR) repertoire analysis, and recent single-cell sequencing has made it possible to obtain information about TCR pairs. In our previous study, cytomegalovirus (CMV) pp65-specific T-cell response restricted by a single human leukocyte antigen (HLA) class I allotype was observed in an individual. Therefore, to effectively clone an antigen-specific TCR from these T cells, we developed a TCR cloning system that does not require a single cell level. First, we established the improved Jurkat reporter cell line, which was TCRαβ double knock-out and expressed CD8αβ molecules. Furthermore, functional TCRs were directly obtained by reverse TCR cloning using unique CDR3-specific PCR primers after bulk TCR sequencing of activation marker-positive CD8 T cells by NGS. A total of 15 TCRα and 14 TCRβ strands were successfully amplified by PCR from cDNA of 4-1BB-positive CD8 T cells restricted by HLA-A*02:01, HLA-A*02:06, HLA-B*07:02, and HLA-B*40:06. The panels with combinations of TCRα and TCRβ genes were investigated using Jurkat reporter cell line and artificial antigen-presenting cells (APCs). In two TCR pairs restricted by HLA-A*02:01, one TCR pair by HLA-A*02:06, four TCR pairs by HLA-B*07:02, and one TCR pair by HLA-B*40:06, their specificity and affinity were confirmed. The TCR pair of A*02:01/1-1 showed alloreactivity to HLA-A*02:06. The one TCR pair showed a higher response to the naturally processed antigen than that of the peptide pool. This reverse TCR cloning system will not only provide functional information to TCR repertoire analysis by NGS but also help in the development of TCR-T therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hong, Pyo, Baek and Kim.)

Artificial antigen-presenting cells (aAPCs) that stably express particular HLA and co-stimulatory molecules by gene transfer have been developed to effectively stimulate T cells. To investigate whether cytochalsin-B-induced membrane vesicles derived from aAPCs (AP-CIMVs) have similar antigen-presenting functions as a cell-free system, T cell responses to different types of antigen presentation were measured using Jurkat reporter cells. First, the aggregation of AP-CIMV, which affects the measurement of function, was inhibited by nuclease treatment to produce uniform AP-CIMVs. The Green fluorescent protein (GFP) expression in Jurkat reporter cells was induced in a dose-dependent manner in groups stimulated with anti-CD3 antibody-coated AP-CIMVs and aAPCs, and anti-CD3/CD28 Dynabead. When Jurkat reporter cells expressing specific T cell receptors were stimulated by AP-CIMVs and aAPCs loaded with CMV pp65 peptide, AP-CIMVs showed similar stimulatory effects to that by aAPC. However, when these Jurkat reporter cells were stimulated by aAPCs endogenously expressing CMV pp65 antigen and their AP-CIMVs, the GFP expression rate by AP-CIMVs was 8.4%, which was significantly lower than 53.2% by aAPCs. Although this study showed a limited T-cell-stimulating effect of AP-CIMVs on endogenously processed antigen presentation, these results provide useful information for the development of improved cell-free systems for T cell stimulation in the future.

HLA-DRB1*12:97 differs from HLA-DRB1*12:02:01:01 in codon 63 in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*07:457 differs from HLA-B*07:02:01:01 in codon 117 in exon 3., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mycobacterium tuberculosis infection is generally asymptomatic as latent tuberculosis, but it is still known as the world's leading bacterial cause of death. The diagnosis of latent tuberculosis infection relies on the evidence of cellular immunity to mycobacterial antigens. Since the association between HLA class II and tuberculosis infection has been reported in several population groups, a detailed study on the CD4 + T cell response to major tuberculosis antigens is needed. To elucidate which HLA class II allotypes in an individual are preferentially used in tuberculosis, CD4 + T cells specific to TB10.4, Ag85b, ESAT-6, and CFP-10 of Mycobacterium tuberculosis antigens were analyzed comprehensively. A total of 33 healthy donors were analyzed by ex vivo and cultured ELISPOT using panels of artificial antigen-presenting cells expressing a single HLA class II allotype. The CD4 + T cell responses were increased by an average of 39-fold in cultured ELISPOT compared with ex vivo ELISPOT. In ex vivo and cultured ELISPOT, CD4 + T cell responses showed significantly higher by HLA-DR than those of HLA-DQ and HLA-DP locus. In cultured ELISPOT, 9 HLA-DR allotypes, 4 HLA-DQ allotypes, and 3 HLA-DP allotypes showed positive CD4 + T cell responses. Among ten donors with positive CD4 + T cell responses when tested for mixed Mycobacterium tuberculosis antigens, seven donors were positive for only a single allotype, and three were positive for two allotypes in an individual. However, only one allotype was used for a single antigen-specific response when a single tuberculosis antigen was used individually. These results on the distribution of HLA class II allotypes showing high CD4 + T-cell responses to Mycobacterium tuberculosis antigens and the intra-individual allotype dominance will provide valuable information for understanding the immunobiology and immunogenetics of tuberculosis, which can contribute to the development of more effective vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Hyun, Jo, Baek, Kim, Sohn and Kim.)

Recently, long synthetic peptides or in silico-predicted epitope peptides have been used to identify T cell epitopes, but these approaches may not be suitable for investigating naturally processed epitopes. Here, mRNAs, including fragments or predicted epitope sequences of HCMV pp65 antigen, were generated by in vitro transcription following transcriptionally active PCR. Then, artificial antigen-presenting cells (aAPCs) expressing a single HLA allotype were transfected with mRNAs to identify epitopes in donors with T cell responses that recognize pp65 antigen restricted to HLA-A*02:01, -A*02:06, or -B*07:02. T cells restricted to a particular HLA allotype showed positive responses in some of the 10 fragment antigens. Among predicted epitopes within these positive fragments, three epitopes of HLA-A*02:01, -A*02:06, and -B*07:02 were confirmed. In addition, T cells expanded by anti-CD3 stimulation for two weeks could also be effectively used for the identification of these T cell epitopes, although there were individual differences. These results demonstrated that fragment antigens and epitopes can be rapidly generated using mRNA, and naturally processed antigenic regions can be detected using aAPCs without a T cell cloning procedure. This method will help to identify novel T cell epitopes for developing immunotherapy and vaccines against infectious diseases and cancer.

HLA-B*51:353 differs from HLA-B*51:01:01:01 in codon 95 in exon 3., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Common human coronaviruses have been circulating undiagnosed worldwide. These common human coronaviruses share partial sequence homology with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, T cells specific to human coronaviruses are also cross-reactive with SARS-CoV-2 antigens. Herein, we defined CD4 + T cell responses that were cross-reactive with SARS-CoV-2 antigens in blood collected in 2016-2018 from healthy donors at the single allele level using artificial antigen-presenting cells (aAPC) expressing a single HLA class II allotype. We assessed the allotype-restricted responses in the 42 individuals using the aAPCs matched 22 HLA-DR alleles, 19 HLA-DQ alleles, and 13 HLA-DP alleles. The response restricted by the HLA-DR locus showed the highest magnitude, and that by HLA-DP locus was higher than that by HLA-DQ locus. Since two alleles of HLA-DR, -DQ, and -DP loci are expressed co-dominantly in an individual, six different HLA class II allotypes can be used to the cross-reactive T cell response. Of the 16 individuals who showed a dominant T cell response, five, one, and ten showed a dominant response by a single allotype of HLA-DR, -DQ, and -DP, respectively. The single allotype-restricted T cells responded to only one antigen in the five individuals and all the spike, membrane, and nucleocapsid proteins in the six individuals. In individuals heterozygous for the HLA-DPA and HLA-DPB loci, four combinations of HLA-DP can be expressed, but only one combination showed a dominant response. These findings demonstrate that cross-reactive T cells to SARS-CoV-2 respond with single-allotype dominance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hyun, Lee, Jo, Baek, Kim, Sohn and Kim.)

Introduction: Middle East Respiratory Syndrome (MERS) caused by MERS-coronavirus (CoV) is a lower respiratory tract disease characterized by a high mortality rate. MERS-CoV spread from Saudi Arabia to other countries, including South Korea. Dysfunction of the human leukocyte antigen (HLA) system has many effects due to genetic complexity and its role in the adaptive immune response. We investigated the association of HLA class I and II alleles with MERS-CoV in 32 patients with MERS., Methods: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 were genotyped by polymerase chain reaction sequence-based typing., Results: HLA-DQB1*03:02 are significantly associated with moderate/mild cases of MERS-CoV. Other alleles are no statistical significance., Conclusions: Treatment strategies based on current research on the HLA gene and MERS-CoV will provide potential therapeutic targets., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Purpose: Immune responses for cancer cells can be altered according to genetic variation of human leukocyte antigen (HLA). Association of HLA polymorphism with risk of various cancer types is well known. However, the association between HLA and glioblastoma (GBM) remains uncertain. We sought to evaluate the association of HLA polymorphism with risk of GBM development in Koreans., Materials and Methods: A case-control study was performed to identify the odds ratios (OR) of HLA class I and II genes for GBM. The control group consisted of 142 healthy Korean volunteers, and the GBM group was 80 patients with newly diagnosed GBM at our institution. HLA class I (-A, -B, and-C) and class II (-DR, -DQ, and-DP) genotyping was performed by high-resolution polymerase chain reaction (PCR)-sequence-based typing (PCR-SBT) methods., Results: There were significantly decreased frequencies of HLA-A*26:02 (OR 0.22 CI 0.05-0.98), HLA-C*08:01 (OR 0.29 CI 0.10-0.87), and HLA-DRB1*08:03 (OR 0.32 CI 0.11-0.98), while there was significantly increased frequency of HLA-C*04:01 (OR 2.29 CI 1.05-4.97). In analysis of haplotypes, the frequency of DRB1*14:05-DQB1*05:03 was significantly decreased (OR 0.22 CI 0.05-0.98)., Conclusion: This study suggests that genetic variations of HLA may affect GBM development in Koreans. Further investigations with larger sample sizes are needed to delineate any potential role of the HLA polymorphisms in the pathogenesis of GBM development., Competing Interests: The authors declare no conflicts of interest.

Smartphone is one of the essential items. However, it may negatively affect a user's mental health when it is overused. The study aimed to investigate associations of smartphone overuse with depression, anxiety, and the relationship with other addictive behaviors and disorders. A total of 2,509 subjects were randomly selected through a one-person-per-household method. Smartphone Overuse Screening Questionnaire (SOS-Q) and the Korean version of the Composite International Diagnostic Interview (K-CIDI) were used. Linear regression and Pearson correlation analyses were performed to evaluate associations of smartphone overuse with depression, anxiety, and relationship with other addictive psychiatric disorders respectively. Among 2509 participants, 138 (14.76%) demonstrated smartphone overuse. Participants who used their smartphones for more than three hours a week were more likely to be single and females compared to those who used their smartphones for less than three hours a week. Smartphone overuse showed significant associations with depression, anxiety disorder, and a significant relationship with internet and game overuse, alcohol dependence, and nicotine dependence disorder. Internet-related behavior showed the strongest relationship with smartphone overuse. Although the sample size was adequate, a large number of subjects did not complete the questionnaire. People with psychiatric disorders should be advised to use smartphones in moderation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

HLA-DRB1*09:45 differs from HLA-DRB1*09:01:02:01 in codon 19 in exon 2., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pre- and post-transplantation anti-MICA antibody detection development are associated with an increased rejection risk and low graft survival. We previously generated HLA class I null HEK-293T using CRISPR/Cas9, while MICA and MICB genes were removed in this study. A panel of 11 cell lines expressing single MICA alleles was established. Anti-MICA antibody in the sera of kidney transplant patients was determined using flow cytometric method (FCM) and the Luminex method. In the 44 positive sera, the maximum FCM value was 2879 MFI compared to 28,135 MFI of Luminex method. Eleven sera (25%) were determined as positive by FCM and 32 sera (72%) were positive by the Luminex method. The sum of total MICA antigens, MICA*002, *004, *009, *019, and *027 correlation showed a statistically significant between the two methods (P = 0.0412, P = 0.0476, P = 0.0019, P = 0.0098, P = 0.0467, and P = 0.0049). These results demonstrated that HEK-293T-based engineered cell lines expressing single MICA alleles were suitable for measuring specific antibodies against MICA antigens in the sera of transplant patients. Studies of antibodies to MICA antigens may help to understand responses in vivo and increase clinical relevance at the cellular level such as complement-dependent cytotoxicity., (© 2021. The Author(s).)

While there has been a slew of review studies on suicide measurement tools until now, there were not any reviews focusing on suicide assessment tools available in Korea. This review aimed to examine the psychometric properties of tools developed in Korea or the translated versions from the original tools in their foreign language and to identify potential improvements and supplements for these tools. A literature search was done using the Korean academic information search service, Research Information Service System, to identify the suicide measures to be included in this review. Abstracts were screened to identify which measures were used to assess suicide-related factors. Based on the established inclusion and exclusion criteria, 18 tools remained and we assessed their psychometric properties. The current review indicated several major findings. First, many of the tools did not report predictive validity and even those with predictive validity were based on past suicide attempts. Second, some of the tools overlooked the interactive component for the cause of suicide. In addition, information to supplement the self-reported and clinician-administered reports by collecting reports from the subjects' families and acquaintances is needed. It is also important to develop a screening tool that examines other aspects of an individual's personal life, including unemployment, bereavement, divorce, and childhood trauma. Moreover, tools that have been studied in more diverse groups of the population are needed to increase external validity. Finally, the linguistic translation of the tools into Korean needs to consider other cultural, social, and psychological factors of the sample of interest., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baek, Jo, Kim, Lee, Lee and Jeon.)

Allele frequencies and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 have been rarely reported in South Koreans using unambiguous, phase-resolved next generation DNA sequencing. In this study, HLA typing of 11 loci in 173 healthy South Koreans were performed using next generation DNA sequencing with long-range PCR, TruSight® HLA v2 kit, Illumina MiSeqDx platform system, and Assign™ for TruSight™ HLA software. Haplotype frequencies were calculated using the PyPop software. Direct counting methods were used to investigate the association with DRB1 for samples with only one copy of a particular secondary DRB locus. We compared these allele types with the ambiguous allele combinations of the IPD-IMGT/HLA database. We identified 20, 40, 26, 31, 19, 16, 4, and 16 alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, respectively. The number of HLA-DRB3/4/5 alleles was 4, 5, and 3, respectively. The haplotype frequencies of most common haplotypes were as follows: A*33:03:01-B*44:03:01-C*14:03-DRB1*13:02:01-DQB1*06:04:01-DPB1*04:01:01 (2.89%), A*33:03:01-B*44:03:01-C*14:03 (4.91%), DRB1*08:03:02-DQA1*01:03:01-DQB1*06:01:01-DPA1*02:02:02-DPB1*05:01:01 (5.41%), DRB1*04:05:01-DRB4*01:03:01 (12.72%), DQA1*01:03:01-DQB1*06:01:01 (13.01%), and DPA1*02:02:02-DPB1*05:01:01 (30.83%). In samples with only one copy of a specific secondary DRB locus, we examined its association with DRB1. We, thus, resolved 10 allele ambiguities in HLA-B, -C (each exon 2+3), -DRB1, -DQB1, -DQA1, and -DPB1 (each exon 2) of the IPD-IMGT/HLA database. Korean population was geographically close to Japanese and Han Chinese populations in the genetic distances by multidimensional scaling (MDS) plots. The information obtained by HLA typing of the 11 extended loci by next generation sequencing may be useful for more exact diagnostic tests on various transplantations and the genetic population relationship studies in South Koreans., Competing Interests: The authors have declared that no competing interests exist.

HLA-A*24:514N differs from HLA-A*24:02:01:01 in codon 167 in exon 3., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*13:144 differs from HLA-B*13:01:01:01 in codon 12 in exon 2., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Within an individual, six different HLA class II heterodimers are expressed co-dominantly by two alleles of HLA-DR, -DQ, and -DP loci. However, it remained unclear which HLA allotypes were used in T cell responses to a given antigen. For the measurement of the CD4 + T cell responses restricted by a single HLA allotype, we established a panel of artificial antigen-presenting cells (aAPCs) expressing each single HLA allele of 20 HLA-DRB1, 16 HLA-DQ, and 13 HLA-DP alleles. CD4 + T cell responses to cytomegalovirus (CMV) pp65 restricted by single HLA class II allotype defined in 45 healthy donors. The average magnitude of CD4 + T cell responses by HLA-DR allotypes was higher than HLA-DQ and HLA-DP allotypes. CD4 + T cell responses by DRA*01:01/DRB1*04:06, DQA1*01:02/DQB1*06:02, DPA1*02:02/DPB1*05:01 were higher among the other alleles in each HLA-DR, -DQ, and -DP locus. Interestingly, the frequencies of HLA-DR alleles and the positivity of specific allotypes showed an inverse correlation. One allotype within individuals is dominantly used in CD4 + T cell response in 49% of donors, and two allotypes showed that in 7% of donors, and any positive response was detected in 44% of donors. Even if one individual had several dominant alleles, CD4 + T cell responses tended to be restricted by only one of them. Furthermore, CD8 + and CD4 + T cell responses by HLA class I and class II were correlated. Our results demonstrate that the CD4 + T cell preferentially use a few dominant HLA class II allotypes within individuals, similar to CD8 + T cell response to CMV pp65., Competing Interests: H-JS and H-IC were employed by the company ViGenCell Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hyun, Jo, Lee, Kim, Baek, Sohn, Cho and Kim.)

HLA genes play a pivotal role for successful hematopoietic stem cell transplantation (HSCT). There is an increasing need for sophisticated screening of donor HLA genotypes for unrelated HSCT. Next generation sequencing (NGS) has emerged as an alternative for classical Sanger sequence for HLA typing. In this study, HLA-A, -B, and -DRB1 alleles were genotyped at the allelic (6-digit) level using MiSeqDx in 26,202 volunteers from the Korean Network for Organ Sharing. Exon 2 and 3 of HLA-A and -B and exon 2 of HLA-DRB1 were amplified by polymerase chain reaction (PCR) and each allele was determined by matching the targeted exons and the reference sequence consisting of the IPD-IMGT/HLA Database. Seventy alleles of HLA-A, 102 alleles of HLA-B, and 69 alleles of HLA-DRB1 were identified. According to common and well-documented catalogs, 34 alleles in HLA-A, 61 in HLA-B, and 45 in HLA-DRB1 locus were common alleles, and 12, 14, and 11 kinds, were well-documented alleles, respectively. Thirteen novel alleles including 3 alleles in HLA-A, 8 alleles in HLA-B, and 2 alleles in HLA-DRB1 loci were found. Ten haplotypes with a frequency of more than 1.0% accounted for 22.4% of the total haplotype frequencies. Cis/trans ambiguities of HLA-A and -B loci by combination of exons 2 and 3 were analyzed to be 0.17% of 3 and 3.95% of 22 genotypes, respectively. This information on rare and novel alleles found by accurate HLA typing with NGS may be helpful for unrelated HSCT among Koreans., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Some HLA alleles have been shown to be associated with susceptibility to cytomegalovirus (CMV) disease incidence in vitro. The objective of this study was to identify correlations between donor HLA allotypes and CMV disease incidence in patients with acute myeloid leukemia who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). Methods and materials we retrospectively analyzed the medical records of 613 donors and recipients with acute myeloid leukemia who had received an allogeneic HSCT from matched sibling (n = 260), unrelated (n = 168), or haploidentical (n = 186) donors, from 2012 to 2017. The HLA-A, -B, -C, and -DRB1 allotypes in the donors were determined using sequence-based typing. Overall, CMV disease incidence was significantly associated with three genotype alleles, HLA-A*30:04:01G, -B*51:01:01G, and -DRB1*09:01:02G. In the donor CMV IgG seropositive subgroup, CMV disease incidence was significantly associated with HLA-B*51:01:01G and -DRB1*09:01:02G. In the IgG seropositive donors in the unrelated allo-HSCT subgroup CMV disease incidence was also significantly associated with HLA-B*51:01:01G. In the CMV seropositive donors in the haploidentical allo-HSCT subgroup, the incidence of CMV disease was significantly associated with HLA-A*24:02:01G and -DRB1*09:01:02G. HLA-DRB1*13:02:01G was a protective marker among IgG seropositive donors in the unrelated allo-HSCT recipient category. Discussion and conclusions The incidence of CMV disease among HSCT recipients varies according to donor HLA alleles and the donor CMV IgG serostatus. Certain donor HLA alleles can be considered to be risk or protective markers. Donors' HLA types and CMV IgG serostatus should be considered in donor selection., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*33:03:42 differs from HLA-A*33:03:01:01 in codon 90 in exon 2., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Autoimmune thyroid disease (AITD) is predominant in females and has been focused on the sexual diploid in immune response. The IL-1 receptor-associated kinase 1 (IRAK1) gene on the X chromosome was recently suggested as strong autoimmune disease-susceptible loci, second to the major histocompatibility complex region. We investigated the frequency of IRAK1 single-nucleotide polymorphisms (SNPs) in children with AITD. In this study, we observed that SNPs of IRAK1 including rs3027898, rs1059703, and rs1059702 in 115 Korean AITD pediatric patients (Graves' disease = 74 [females = 52/males = 22]; Hashimoto disease [HD] = 41 [females = 38/males = 3]; thyroid-associated ophthalmopathy [TAO] = 40 (females = 27/males = 13); without TAO = 75 (females = 63/males = 12); total males = 25, total females = 90; mean age = 11.9 years) and 204 healthy Korean individuals (males = 104/females = 100). The data from cases and controls were analyzed from separate sex-stratified or all combined by χ 2 test for categorical variables and Student t test for numerical variables. Our study revealed that SNPs of IRAK1-associated HD and without TAO but Graves' disease and TAO were not found significant. When cases and controls were analyzed by separate sex, we found that rs3027898 AA, rs1059703 AA, and rs1059702 GG showed disease susceptibility in female AITD, HD, and without TAO. Also, all rs3027898, rs1059703, and rs1059702 were found to be in strong linkage disequilibrium (D' = 0.96-0.98, r2 = 0.83-0.97). The haplotype of 3 SNPs was higher in AITD than in controls (CGA, r2 = 5.42, P = 0.019). Our results suggest that IRAK1 polymorphisms may contribute to the pathogenesis of HD, AITD, and without thyroid-associated ophthalmopathy for females., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to develop a screening questionnaire to distinguish high-risk individuals associated with game overuse from casual internet users. Reliability, validity, and diagnostic ability were evaluated for the newly developed Game Overuse Screening Questionnaire (GOS-Q). Preliminary items were assessed by 50 addiction experts online and 30 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. Finally, 150 people were used in the analysis after excluding eight non-respondents. GOS-Q, Young's internet addiction scale, and Korean scale for internet addiction were used to assess concurrent validity. Internal consistency and item-total correlations were favorable (α= 0.96, r= 0.47-0.82). Test-retest reliability was moderate in size (r= 0.74). GOS-Q showed superior concurrent validity, and the highest correlation with Y-Scale (r= 0.77). The construct validity was marginally supported by a six-factor model using exploratory factor analysis. The area under the Receiver Operating Characteristic curve was 0.945. The high-risk addiction group was effectively characterized by a cut-off point of 38.5, with a sensitivity of 0.87 and a specificity of 0.88. Overall, the current study supports the use of GOS-Q as a reliable screening tool in a variety of settings., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

(1) Background: Autoimmune thyroid diseases (AITDs) are female predominant and much attention has been focused on G protein-coupled receptor 174 ( GPR174) and integral membrane protein 2A ( ITM2A) on the X chromosome as Grave's disease (GD) susceptible locus. (2) Methods: We genotyped four single nucleotide polymorphisms (SNPs), rs3810712, rs3810711, rs3827440, and rs5912838, of GPR174 and ITM2A in 115 Korean children with AITD (M = 25 and F = 90; GD = 74 (14.7 ± 3.6 years), HD = 41 (13.4 ± 3.2 years); GD-thyroid-associated ophthalmopathy (TAO) = 40, GD-non-TAO=34) and 204 healthy Korean individuals (M = 104 and F = 100). The data were analyzed by sex-stratified or combined. (3) Results: Three SNPs, rs3810712, rs3810711 and rs3827440, were found to be in perfect linkage disequilibrium ( D ' = 1, r 2 = 1). In AITD, HD, GD, GD-TAO, and GD-non-TAO patients, rs3827440 TT/T and rs5912838 AA/A were susceptible and rs3827440 CC/C and rs5912838 CC/C were protective genotypes. When analyzed by sex, rs3827440 TT and rs5912838 AA were susceptible and rs3827440 CC and rs5912838 CC were protective genotypes in female AITD, GD, GD-TAO, and GD-non-TAO subjects. In male AITD patients, rs3827440 T and rs5912838 A were susceptible and rs3827440 C and rs5912838 C were protective genotypes. (4) Conclusions: Polymorphisms in GPR174 and ITM2A genes on the X chromosome might be associated with AITD in Korean children.

HLA-DRB1*04:05:21 differs from HLA-DRB1*04:05:01:01 in codon 83 in exon 2., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*15:529 differs from HLA-B*15:01:01:01 in codon 138 in exon 3., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*51:284 differs from HLA-B*51:01:01:01 in codon 44 in exon 2., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*54:41 differs from HLA-B*54:01:01:01 in codon 121 in exon 3., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*02:877 differs from HLA-A*02:06:01:01 in codon 183 in exon 3., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*44:454 differs from HLA-B*44:03:02:01 in codon 81 in exon 2., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Anxiety sensitivity (AS) refers to the tendency to fear physical sensations associated with anxiety due to concerns about potential physical, social, or cognitive consequences. Many previous studies were limited by the use of the anxiety sensitivity index (ASI) or the ASI-revised (ASI-R), which are both measurements with unitary or unstable structures. No recent study that has utilized the ASI-3 examined the relations between AS dimensions and depression. Thus, we examined multiple relationships between AS and anxiety disorders and depression using the ASI-3., Methods: The total sample consisted of 667 outpatients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth text revision as assessed by a structured clinical interview. There were eight patient groups: multiple anxiety disorder, major depressive disorder (MDD), panic disorder (PD), social phobia (SP), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and anxiety disorder not otherwise specified (AD NOS). We conducted one-way analysis of variances and post hoc tests to compare the ASI-3 total and subscale scores across the groups., Results: The physical concern score was higher in patients with PD than patients with MDD, SP, OCD, or GAD. The social concern score was higher in the SP group than those with MDD, PD, GAD, and AD NOS. Patients with GAD and PTSD showed higher cognitive concern scores than the patients with PD., Conclusion: Results partially replicated the relationship between PD and physical concern, between SP and social concern, and between GAD and cognitive concern examining the relationships between AS dimensions and anxiety disorders., (© 2019 Wiley Periodicals, Inc.)

The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves' disease [GD]: 71, Hashimoto's disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim of the study was to evaluate the influence of the depth of local anesthesia application on procedural pain during lumbar transforaminal epidural steroid injection., Design: Sixty-eight patients were enrolled who were scheduled for single-level, unilateral fluoroscopically guided lumbar transforaminal epidural steroid injection. Patients were randomly allocated to receive either subcutaneous local anesthesia (group S) or deep local anesthesia (group D) for transforaminal epidural steroid injection. The data related to pain and technical performance during the procedure was compared. In addition, the incidence of injection site soreness was assessed 2 wks after transforaminal epidural steroid injection., Results: Sixty-seven patients completed all assessments (group S, n = 33; group D, n = 34). There was no significant difference in procedural pain and discomfort level between the groups (P = 0.151, P = 0.183, respectively). Patients in group D showed lower behavioral pain scores (P = 0.017). There was no significant difference in the numbers of needle manipulations, fluoroscopy time, and radiation dose during the procedure between the groups. Two patients in group S and three in group D complained of injection site soreness after transforaminal epidural steroid injection for a few days, but there was no significant difference in its incidence (P = 0.667)., Conclusions: Deep local anesthesia to reduce procedural pain during transforaminal epidural steroid injection seems to have no significant clinical benefit compared with conventional subcutaneous local anesthesia., To Claim Cme Credits: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Reduce procedural pain by considering clinical factors of the patient during fluoroscopically guided lumbar transforaminal epidural injections.Upon completion of this article, the reader should be able to: (1) Understand the potential impact of procedural pain on the performance of transforaminal epidural steroid injections; (2) Distinguish cutaneous nociceptive afferents from nociceptive afferents in muscle; and (3) Explain the factors to reduce procedural pain during fluoroscopically guided lumbar transforaminal epidural injections., Level: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

HLA-C*06:66 differs from HLA-C*06:02:01:01 in codon 151 in exon 3., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*46:67 differs from HLA-B*46:01:01 in codons 94, 95, and 103 in exon 3., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)