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To determine the incidence rate of narcolepsy in South Korea and closely examine the relationship between narcolepsy, which is believed to be an autoimmune response, and other systemic autoimmune diseases. We examined data from the South Korean nationwide health insurance claims database from 2010 to 2019. Our study included patients with narcolepsy as well as age- and sex-matched controls without narcolepsy. We estimated the incidence of narcolepsy and the odds ratio of narcolepsy and associated autoimmune comorbidities in South Korea. We identified 8710 patients with narcolepsy (59.8% men and 40.2% women). The incidence of narcolepsy was 0.05%. Patients with narcolepsy were at a significantly high risk of ankylosing spondylitis, rheumatoid arthritis, and Sjögren's syndrome, which diseases are known to be related to human leukocyte antigen (HLA) genes. Narcolepsy is closely related to systemic autoimmune diseases, particularly those related to HLA genes. • As the relationship between narcolepsy and other systemic autoimmune diseases is yet to be defined, we closely examined the relationship based on national insurance claims database. • As a result, we found narcolepsy to be highly associated with several systemic autoimmune diseases such as ankylosing spondylitis, rheumatoid arthritis and Sjogren's syndrome.These three autoimmune diseases are highly associated with the HLA gene. • Narcolepsy is highly associated with DQB106:02, which may explain its increased odds of comorbidity. [ABSTRACT FROM AUTHOR]

The immunogenicity and protective efficacy of inactivated clade 2.3.2.1c (rgKA435) and clade 2.3.4.4c (rgES2) H5Nx vaccines, which are representatives of an avian influenza antigen bank in Korea, were examined in mice. Mice were vaccinated twice and then challenged with homologous virus. Hemagglutinin inhibition and serum neutralizing antibody titers in the rgES2-vaccinated group were higher (4.4 ± 1.7 and 10.8 ± 2.3 log 2 , respectively) than those in the rgKA435-vaccinated group (2.8 ± 1.1 and 2.5 ± 0.9 log 2 , respectively). rgES2 conferred 100% protection, with no morbidity, no severe body weight loss, and no virus replication in any of the tissues tested. By contrast, 80% of mice in the rgKA435 group survived. One mouse in this group died at 10 dpi. Virus titers in the lung and turbinate were 102.5–3.5 TCID 50 /0.1 ml at 3–7 dpi and 101.5 TCID 50 /0.1 ml at 3–5 dpi, respectively. In particular, the viral titer in the turbinate from the rgKA435 group at 3 dpi was significantly lower than that in the equivalent control group (p < 0.05). The data suggest that both of these antigen bank vaccines are promising candidates for further evaluation in humans. [ABSTRACT FROM AUTHOR]

• Five inactivated vaccines were generated for Korean AI national antigenic bank for HPAI emergency preparedness. • Vaccines provide good protection in SPF chickens against homologous HPAI virus. • Vaccines produce high immunity from a single dose with sufficient antigen mass. • Vaccines induce long-lasting antibody responses to prevent mortality and virus shedding. The occurrence of severe outbreaks of highly pathogenic avian influenza in Korea led to establishment of a national antigen bank for emergency preparedness. Here, we developed five vaccines for this bank (clade 2.3.2.1C, clade 2.3.4.4A, B, C, and D) by reverse genetics, inactivated them with formalin, and evaluated the protective efficacy and potency of serial dilutions against lethal homologous challenge in specific-pathogen-free chickens. After vaccination with one dose, each vaccine resulted in 100% survival, with no clinical symptoms, or lack of detectable virus shedding, and high levels of pre-challenge protective immunity (8.4–10.2 log 2). After vaccination with one-tenth of the full dose, protection was similar to that with the full dose. After vaccination with one-hundredth of the initial dose, survival was 20–80%, and all vaccines showed virus shedding. Four vaccines (excluding clade 2.3.2.1C) had satisfactory potency. In antibody-persistence tests, all vaccines maintained long-lasting protective immunity. Our results suggest that inactivated reverse-genetics vaccines genetically matched to outbreak viruses provide adequate protection after a single vaccination. [ABSTRACT FROM AUTHOR]

The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population. All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units. A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E > c > e > C > K > Jk(a) > Lu(a) > S > Fy(a) > Fy(b) > Jk(b) > Di(b) > Di(a) in the total population and E > c > e > C > Jk(a) > Fy(a) > Fy(b) > S > K > Lu(a) > Jk(b) > Di(b) > Di(a) in male patients. The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions. [ABSTRACT FROM AUTHOR]

Presence of antibodies to donor specific human leukocyte antigens (HLA) is a well-known risk factor associated with outcome in solid organ transplantation. Recent studies have suggested that non-HLA antibodies could also be associated with outcomes in heart transplantation (HTx). We sought to assess the combined effect of donor specific HLA antibodies and non-HLA anti-vimentin antibodies on graft outcome in Korean HTx patients. Pre-transplant serum was analyzed in 192 adult patients who underwent HTx from January 2014 to December 2016 in four large transplant centers in Korea. Demographic and outcome data were obtained from the Korean Organ Transplantation Registry (KOTRY), an organization established in 2014 to collect data on transplant patients. Donor specific HLA antibodies (DSA) were present in 28 (14.6%) patients, while anti-vimentin antibodies were present in 98 (51.0%) patients. Anti-vimentin antibodies were more prevalent in males (p=0.029), but there were no significant differences in other demographic factors. Positive DSA was associated with a significantly higher rate of 3-month graft failure (log-rank p=0.001). Anti-vimentin antibody positivity was also an independent predictor for 3-month and 1-year graft failure (HR adjust 5.21, 95% CI 1.66-16.37, p=0.005; HR adjust 3.45, 95% CI 1.47-8.09, p=0.004, respectively). In DSA(+) patients, anti-vimentin antibody positivity further discriminated 1-year graft survival (long-rank p=0.002). In our analysis of Korean HTx patients, DSA and anti-vimentin antibodies were both associated with increased risk of graft failure at 1 year. Additionally, anti-vimentin antibody positivity was able to further discriminate outcome in patients undergoing pre-sensitized HTx. Pre-transplant assessment of anti-vimentin antibodies could help predict outcome and tailor immunotherapy in specific patients. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly fatal viral disease affecting pigs. It is caused by the ASF virus (ASFV), and causes serious economic losses to the swine industry worldwide, including in Korea. Commercially available enzyme-linked immunosorbent assay (ELISA) kits for detecting anti-ASFV antibodies are used for the diagnosis and surveillance of ASF. In this study, an ELISA was developed to detect anti-ASFV antibodies using two recombinant proteins, p22 and p30, from genotype II ASFV. Recombinant transmembrane domain-deleted p22 (p22∆TM) and p30 were expressed in E.coli vector system pET32a and mixed for use as antigens in indirect ELISA. The p22∆TM/p30-based indirect ELISA was validated using 31 sera from genotype I ASFV-infected pigs and 1133 sera from uninfected pigs. Area under the curve of this test was 0.999 [95 % concentration interval 0.992–1.000], and sensitivity and specificity were 93.5 % and 99.8 %, respectively. The between run coefficient of variation for internal quality control serum was 6.61 %. In the seroconversion analysis, the p22∆TM/p30-based indirect ELISA showed equal or better ability to detect antibodies in pigs experimentally challenged with ASFV p72 genotypes I and II (p < 0.05). In conclusion, the p22∆TM/p30-based indirect ELISA is a reliable diagnostic method for detecting anti-ASFV antibodies. • Recombinant transmembrane domain-deleted p22 (p22∆TM) and p30 antigen-based indirect ELISA was developed to detect anti-ASFV antibodies in pigs. • The p22∆TM/p30-based indirect ELISA showed equal or better ability to detect antibodies in pigs experimentally challenged with ASFV p72 genotypes I and II. [ABSTRACT FROM AUTHOR]

Human astroviruses (HAstVs) occur worldwide and are known to the causative agents of diarrhea in infants and elderly patients with immune dysfunction. This study aimed to identify recombinant HAstV strains and characterize rare genotypes. The full-length genome of a recombinant HAstV strain isolated from the stool sample of a patient with acute gastroenteritis from South Korea was amplified using three pairs of previously designed primers and seven newly designed primers. The recombinant HAstV was 6757-bp long and contained three sequential open reading frames (ORFs), designated as ORF1a (2781 bp), ORF1b (1548 bp), and ORF2 (2349 bp). Our findings suggested that a recombination event had occurred between ORF1b and ORF2 of the isolated strain, with a recombination breakpoint at 4081 bp. To our knowledge, this is the first study to reveal the complete nucleotide sequence of a recombinant HAstV strain from South Korea. Our study findings might be useful for identifying other recombinant HAstV strains and for developing vaccines against this pathogenic virus. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the clinical performance of STANDARD F COVID-19 Ag FIA (SD Biosensor Inc., Gyeonggi-do, Republic of Korea), a rapid antigen detection test (RADT) for diagnosing SARS-CoV-2, in patients attended at the Emergency Department with signs or symptoms compatible with COVID-19 that had started in the last 5 days. The clinical performance of the antigen test was compared with RT-PCR, the reference standard. We included 663 specimens from non-repetitive patients. Clinical sensitivity and specificity were 84.0% (95% CI 76.1−89.7) and 99.6% (95% CI 98.5−99.9), respectively. The positive and negative predictive values were 98.1% (95% CI 92.7−99.7) and 96.4% (95% CI 94.4−97.7), respectively. The kappa index agreement between RT-PCR and the RADT was 0.89 (95% CI 0.84−0.93). We concluded that STANDARD F COVID-19 Ag FIA is an excellent first-line RADT method to diagnose symptomatic patients in the emergency department. [ABSTRACT FROM AUTHOR]

RT-PCR is the gold standard to detect SARS-CoV-2, however, its capacity is limited. We evaluated an automated antigen detection (AAD) test, Elecsys SARS-CoV-2 Antigen (Roche, Germany), for detecting SARS-CoV-2. We compared the limit of detection (LOD) between AAD test, rapid antigen detection (RAD) test; SARS-CoV-2 Rapid Antigen Test (SD Biosensor, Korea), and in-house RT-PCR test. LOD results showed that the AAD test was 100 fold more sensitive than the RAD test, while the sensitivity of the AAD test was comparable to the RT-PCR test. The AAD test detected between 85.7% and 88.6% of RT-PCR-positive specimens collected from COVID-19 patients, false negative results were observed for specimens with Ct values >30. Although clinical sensitivity for the AAD test was not superior or comparable to the RT-PCR test in the present study, the AAD test may be an alternative to RT-PCR test in terms of turn-around time and throughput. [ABSTRACT FROM AUTHOR]

Presence of antibodies to donor specific human leukocyte antigens (HLA) is a well-known risk factor associated with outcome in heart transplantation (HTx). Recent studies have suggested that non-HLA antibodies could also be associated with outcomes. We sought to assess the combined effect of donor specific HLA antibodies and non-HLA anti-vimentin antibodies on graft outcome in Korean HTx patients. Pre-transplant serum was analyzed in 192 adult patients who underwent HTx from January 2014 to December 2016 in four large transplant centers in Korea. Demographic and outcome data were obtained from the Korean Organ Transplantation Registry (KOTRY), an organization established in 2014 to collect data on transplant patients. Donor specific HLA antibodies (DSA) were present in 28 (14.6%) patients, while anti-vimentin antibodies were present in 98 (51.0%) patients. Anti-vimentin antibodies were more prevalent in males (p=0.029), but there were no significant differences in other demographic factors. Positive DSA was associated with a significantly higher rate of 3-month graft failure (log-rank p=0.001). Anti-vimentin antibody positivity was also an independent predictor for 3-month and 1-year graft failure (HR adjust 5.21, 95% CI 1.66-16.37, p=0.005; HR adjust 3.45, 95% CI 1.47-8.09, p=0.004, respectively). In DSA(+) patients, anti-vimentin antibody positivity further discriminated 1-year graft survival (long-rank p=0.002). In our analysis of Korean HTx patients, presence of DSA and anti-vimentin antibodies were both associated with increased risk of graft failure at 1 year. Additionally, anti-vimentin antibody positivity further discriminated outcome in pre-sensitized patients. Pre-transplant assessment of anti-vimentin antibodies could help predict outcome and tailor immunotherapy in specific populations. [ABSTRACT FROM AUTHOR]

Background Mitochondria have a key role in cell survival, signaling, metabolism, and homeostasis. However, whether their biological properties affected by differentiation status of cells are not well known. This study aimed to compare structural and functional differences of mitochondria between differentiated cancer cells and undifferentiated cancer stem cells. Methods Glioma stem cells (GSCs) were cultured in stem cell culture conditions to maintain their stem cell properties or serum culture conditions to induce their differentiation. Characteristics of GSCs are analyzed through sphere-forming ability and expression of stem cell/differentiation markers. Mitochondrial biogenesis and structure was examined by transmission electron microscopy analysis. Bioinformatics analysis, qRT-PCR, glucose uptake assay and lactate production assays were applied to reveal metabolic difference. Results GSCs grown in serum culture conditions showed lower stem cell markers expression and higher differentiation markers compared to GSCs grown in stem cell culture conditions. In the serum culture conditions, biogenesis of mitochondria was significantly increased. RNA sequencing analysis using GSCs grown in stem cell culture or serum culture conditions revealed that differentiated GSCs are enriched with mitochondria-related gene signature. Also, glucose metabolism was increased in GSCs grown in stem cell culture conditions compared to serum culture conditions. Conclusions Under different culture conditions, GSCs show different mitochondrial biogenesis and cellular metabolism. Understanding mitochondria properties in cancer may lead us to discover a novel therapeutic target. Editorial acknowledgement Cancer Growth Regulation Laboratory for technical support and helpful advice. Legal entity responsible for the study The authors. Funding National Research Foundation of Korea (NRF) [grant numbers: 2015R1A5A1009024 and 2017R1E1A1A01074205], the School of Life Sciences and Biotechnology for BK21 Plus, Korea University and Institute of Animal Molecular Biotechnology, Korea University. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]