Background: Daratumumab is a human monoclonal antibody targeting CD38 used widely in various related conditions. Caution is advised when interpreting the pretransfusion tests in daratumumab-treated patients because they may show nonspecific reactions with red blood cells. This paper provides experimental evidence for the false-positive interference phenomena induced by daratumumab in in-vitro and ex-vivo experiments and experimental support for resolving it using dithiothreitol (DTT). Methods: Fifteen crossmatching pairs, four cardiac amyloidosis (CA) patients treated with daratumumab, and three healthy individuals were included. The flow cytometry crossmatch (FCMXM) was conducted with negatively selected T and B cells. After spiking the sera with 500 μg/mL daratumumab, the T and B cells were treated with DTT. The prospective FCMXM was conducted with the sera of CA patients treated with daratumumab. The CD38 expression levels in T, B, and NK cells were measured without and with a DTT or pronase treatment. Results: Five hundred μg/mL of daratumumab spiking was sufficient to elicit a false positive effect in T cell FCMXM. In particular, the administration of 0.1 M DTT efficiently resolved the induced false positivity in flow cytometry. Moreover, DTT caused a decrease in the CD38 expression levels in T, B, and NK cells. Conclusion A typical therapeutic dose of daratumumab causes false-positive FCMXM, which was effectively addressed by a DTT treatment. Therefore, information about the patient’s medical condition and the use of immunotherapeutics, such as daratumumab, is needed, given its impact on diverse CD38-expressing cells.

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.

Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a subtype of CMC caused by gain-of-function (GOF) mutation of the signal transducer and the activator of transcription 1 (STAT1) protein. GOF mutation of STAT1 disrupts Th17 cell differentiation and causes susceptibility to candida infection in mucous membranes. Although genetic testing is crucial to diagnose AD-CMC, a simple and fast diagnostic tool is required for the management and reduction of complications associated with infection. Flow cytometry (FCM) is suggested for the measurement of intracellular phosphorylated STAT1 (pSTAT1) in a stimulated status. Here, we report the application of FCM to show the activation status of STAT signaling in a 24-year-old female patient diagnosed with AD-CMC. Compared to the controls, the patient’s T cells showed increased levels of pSTAT1 after stimulation by interferon-γ and lesser extent of inhibition caused by an inhibitor. To the best of our knowledge, this is the first evaluation of the usefulness of FCM as an alternative diagnostic and monitoring tool of GOF STAT1 in Korea.

Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a subtype of CMC caused by gain-of-function (GOF) mutation of the signal transducer and the activator of transcription 1 (STAT1) protein. GOF mutation of STAT1 disrupts Th17 cell differentiation and causes susceptibility to candida infection in mucous membranes. Although genetic testing is crucial to diagnose AD-CMC, a simple and fast diagnostic tool is required for the management and reduction of complications associated with infection. Flow cytometry (FCM) is suggested for the measurement of intracellular phosphorylated STAT1 (pSTAT1) in a stimulated status. Here, we report the application of FCM to show the activation status of STAT signaling in a 24-year-old female patient diagnosed with AD-CMC. Compared to the controls, the patient’s T cells showed increased levels of pSTAT1 after stimulation by interferon-γ and lesser extent of inhibition caused by an inhibitor. To the best of our knowledge, this is the first evaluation of the usefulness of FCM as an alternative diagnostic and monitoring tool of GOF STAT1 in Korea.

Background: There is limited information describing the presenting characteristics and dynamic clinical changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosed in the early phase of illness. This study is a case series of patients with coronavirus disease 2019 (COVID-19) admitted to 11 hospitals in Korea. Methods: Patients with confirmed SARS-CoV-2 infection by positive polymerase chain reaction (PCR) testing of respiratory specimens by active surveillance that were finally discharged between February 20 and April 30, 2020 were included. Patients were classified into mild and non-mild groups on initial admission according to oxygen demand and Sequential Organ Failure Assessment score, and the mild group was followed up and subgrouped into non-aggravation and aggravation groups. Results: A total of 161 patients with SARS-CoV2 infection were enrolled. Among the mild group of 136 patients, 11.7% of patients experienced clinical aggravation during hospitalization, but there was no initial clinical parameter on admission predicting their aggravation. Fever (odds ratio [OR], 4.56), thrombocytopenia (OR, 12.87), fever (OR, 27.22) and lactate dehydrogenase (LDH) > 300 U/L (OR, 18.35), and CRP > 1 mg/dL (OR, 11.31) significantly indicated aggravation in the 1st, 2nd, 3rd, and 4th 5-day periods, respectively.PCR positivity lasted for a median of 22 days and 32 days after the onset of illness in the nonaggravation and aggravation groups, respectively. Conclusion Old age was associated with early severe presentation. Clinical aggravation among asymptomatic or mild patients could not be predicted initially but was heralded by fever and several laboratory markers during the clinical course.

BACKGROUND: Friedewald equation is the most widely used method for estimating low-density lipoprotein cholesterol (LDL-C) level. However, due to potential over- or underestimation, many studies have used a modified equation. This study aimed to compare estimates by 4 different equations to directly measured LDL-C concentrations in order to propose the most appropriate method for LDL-C estimation in the Korean population. METHODS: We studied data of 4,350 subjects that included total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and LDL-C concentrations that had been measured at one university hospital in Seoul. We investigated 4 equations: LDL-C by Friedewald's original equation (LDL-C(F)) and its 3 modifications. Pearson correlation analysis was performed to compare these estimates to the direct measurement. RESULTS: Pearson correlation analysis revealed a good correlation among all 4 estimated LDL-C values and the directly measured LDL-C value. The Pearson coefficients were 0.951 for LDL-C(F), 0.917 for LDL-C by Hatta equation (LDL-C(H)), 0.968 for LDL-C by Puavilai equation (LDL-C(P)), and 0.983 for LDL-C by Martin equation (LDL-C(M)). Martin equation (LDL-C(M)) resulted in the best approximation (mean difference from the direct measurement, 5.5 mg/dL; mean percentage difference from the direct measurement, 5.1%) and the best agreement with the direct measurement (86.1%). LDL-C(P) resulted in the second-best approximation (mean difference, 7.0 mg/dL; mean percentage difference, 6.2%; concordance, 82.5%). LDL-C(M) was found to be less influenced by TG and HDL-C levels than by LDL-C(F). CONCLUSION: Estimates by Martin equation had the best agreement with direct LDL-C concentrations and both Martin and Puavilai equations were superior to Friedewald equation for estimating LDL-C concentrations in Korean adults.
Adult* ; Cholesterol* ; Dyslipidemias ; Humans ; Lipoproteins* ; Methods* ; Seoul ; Triglycerides

Bartonella henselae causes cat-scratch disease, bacteremia, and various focal infections. Despite the worldwide occurrence of B. henselae infections, reports in humans are rare in Korea. The clinical manifestation of all 5 previously reported cases was lymphadenopathy. Herein, we report a case of bacteremia in a woman who presented with prolonged fever. B. henselae was isolated from a blood specimen by cell culture. Conventional polymerase chain reaction amplification and sequencing of the 16S-23S rRNA intergenic space region confirmed the isolate to be B. henselae. The patient had no underlying immunocompromising conditions and no recent exposure to animals. She was successfully managed with a combination of doxycycline and hydroxychloroquine.
Animals ; Bacteremia* ; Bartonella henselae* ; Bartonella* ; Cat-Scratch Disease ; Cell Culture Techniques ; Chloroquine ; Doxycycline ; Female ; Fever ; Fever of Unknown Origin ; Focal Infection ; Humans ; Hydroxychloroquine ; Korea* ; Lymphatic Diseases ; Polymerase Chain Reaction