Original Article2022-01-01 Diagnostic Immunology
Younhee Park 
, M.D., Ki Ho Hong , M.D., Su-Kyung Lee , M.S., Jungwon Hyun , M.D., Eun-Jee Oh , M.D., Jaehyeon Lee , M.D., Hyukmin Lee , M.D., Sang Hoon Song , M.D., Seung-Jung Kee , M.D., Gye Cheol Kwon , M.D., Su Hwan Kim , B.S., Hyeon-Nam Do , M.S., Ah-Ra Kim , M.S., June-Woo Lee , Ph.D., Sung Soon Kim , Ph.D., and Hyun Soo Kim , M.D., Ph.D.
Abstract : Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies. Methods: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study. Results: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined. Conclusions: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.
Review Article2022-03-01 Diagnostic Genetics
Saeam Shin , M.D., Ph.D., Hye In Woo , M.D., Ph.D., Jong-Won Kim , M.D., Ph.D., Yoonjung Kim M.D. , Ph.D., Kyung-A Lee , M.D., Ph.D.
Abstract : Standardization of cell-free DNA (cfDNA) testing processes is necessary to obtain clinically reliable results. The pre-analytical phase of cfDNA testing greatly influences the results because of the low proportion and stability of circulating tumor DNA (ctDNA). In this review, we provide evidence-based clinical practice guidelines for pre-analytical phase procedures of plasma epidermal growth factor receptor gene (EGFR) variant testing. Specific recommendations for pre-analytical procedures were proposed based on evidence from the literature and our experimental data. Standardization of pre-analytical procedures can improve the analytical performance of cfDNA testing.
Guideline2022-07-01 Clinical Microbiology
Ki Ho Hong , M.D., Gab Jung Kim , Ph.D., Kyoung Ho Roh , M.D., Heungsup Sung , M.D., Jaehyeon Lee , M.D., So Yeon Kim , M.D., Taek Soo Kim , M.D., Jae-Sun Park , Ph.D., Hee Jae Huh , M.D., Younhee Park , M.D., Jae-Seok Kim , M.D., Hyun Soo Kim , M.D., Moon-Woo Seong , M.D., Nam Hee Ryoo , M.D., Sang Hoon Song , M.D., Hyukmin Lee , M.D., Gye Cheol Kwon , M.D., and Cheon Kwon Yoo , Ph.D.
Abstract : Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have announced guidelines for diagnosing coronavirus disease (COVID-19) in clinical laboratories in Korea. With the ongoing pandemic, we propose an update of the previous guidelines based on new scientific data. This update includes recommendations for tests that were not included in the previous guidelines, including the rapid molecular test, antigen test, antibody test, and self-collected specimens, and a revision of the previous recommendations. This update will aid clinical laboratories in performing laboratory tests for diagnosing COVID-19.
Brief Communication2021-07-01 Diagnostic Immunology
Hyunhye Kang , M.D., Jaeeun Yoo , M.D., Sang-Yoon Lee , M.T., and Eun-Jee Oh , M.D., Ph.D.
Abstract : Pretransplant crossmatch (XM) testing is widely used for detecting preformed donor-specific antibodies (DSAs) against human leukocyte antigen (HLA). However, in some cases, there is a positive XM result in the absence of HLA-DSAs, the cause of which was rarely identified. We reviewed the causes of sequential positive XM results at a single center and analyzed the presence of non-HLA antibodies in patients with an unexplained positive pretransplant XM result. Among 251 patients with T-cell/B-cell complement-dependent cytotoxicity (CDC) or flow cytometric crossmatch (FCXM) positivity, HLA-DSAs were confirmed in 88 (35.1%) by a single antigen bead (SAB) assay, 150 (59.8%) used rituximab (anti-CD20), and 13 (5.2%) had neither HLA-DSAs nor a desensitization history. Anti-angiotensin II type 1 receptor IgG and 33 non-HLA antibodies were tested in the 13 patients with an unexplained positive pretransplant XM result, and more than one non-HLA antibody were revealed in all these patients; 11 patients had non-HLA antibodies reported to be associated with graft rejection, and two patients experienced rejection episode after kidney transplantation. Our study suggests considering non-HLA antibodies testing when a CDC or FCXM test is positive without a definite cause. Assessing non-HLA antibodies might be useful for interpreting XM results and evaluating immunologic risk in transplant recipients.
Original Article2022-01-01 Diagnostic Immunology
Sumi Yoon , M.D., Hee-Won Moon , M.D., Ph.D., Hanah Kim , M.D., Ph.D., Mina Hur , M.D., Ph.D., and Yeo-Min Yun , M.D., Ph.D.
Abstract : Background: Recently, two fully automated immunoassays for antinuclear antibody (ANA) screening were introduced: EliA CTD Screen (Thermo Fisher Scientific, Freiburg, Germany) and QUANTA Flash CTD Screen Plus (Inova Diagnostics, San Diego, USA). We evaluated their clinical performance in comparison with the indirect immunofluorescence assay (IIFA) and analyzed samples with discrepant results. Methods: In total, 406 serum samples (206 from patients undergoing routine checkups and 200 from rheumatology clinic patients) were assayed using EliA, QUANTA Flash, and IIFA. We evaluated assay concordance and agreement and confirmed the presence of anti-extractable nuclear antigen (ENA) antibodies in samples with discrepant automated immunoassay and IIFA results. Additionally, we compared the clinical performance of each assay in diagnosing ANA-associated rheumatic disease (AARD) and adjusted the cut-off values. Results: In rheumatology clinic samples, the concordance and agreement were 91.5% and strong between EliA and QUANTA Flash, 79.0% and weak between EliA and IIFA, and 80.5% and moderate between QUANTA Flash and IIFA, respectively. In automated immunoassay-positive, IIFA-negative samples (N=15), all anti-ENA antibodies detected (6/15) were anti-Sjögren’s syndrome antigen A/Ro (Ro60) antibodies. The automated immunoassays and IIFA showed high accuracy for diagnosing AARD, and adjusted cut-off values improved their sensitivities (EliA with 0.56 ratio, 82.9% sensitivity; QUANTA Flash with 9.7 chemiluminescent units, 87.8% sensitivity). Conclusions: The two automated immunoassays showed reliable performance compared with IIFA and can be efficiently used with the IIFA in clinical immunology laboratories. Clinical cut-off values can be adjusted according to the workflow in each laboratory.
Original Article2021-07-01 Clinical Chemistry
Christian Albert , M.D., Michael Haase , M.D., Annemarie Albert , M.D., Martin Ernst , M.D., Siegfried Kropf , Ph.D., Rinaldo Bellomo , M.D., Sabine Westphal , M.D., Rüdiger C. Braun-Dullaeus, M.D., Anja Haase-Fielitz , Pharm.D., and Saban Elitok , M.D.
Abstract : Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC <0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P=0.014). Conclusions: Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.
Brief Communication2021-07-01 Clinical Microbiology
Hyun Soo Seo , M.S., Hyung Sun Chin , B.S.N., Yeon-Hee Kim , M.S., Hye Su Moon , B.S., Kyungnam Kim , B.S., Le Phuong Nguyen , M.D., and Dongeun Yong , M.D., Ph.D.
Abstract : Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.
Review Article2022-05-01 General Laboratory Medicine
Sun Huh , M.D., Ph.D.
Abstract : Background: A bibliometric analysis of the Annals of Laboratory Medicine (ALM) was performed to understand its position in the medical laboratory technology category and to suggest a developmental strategy. Methods: Journal metrics, including the number of articles by publication type, country of authors, total citations, 2-year impact factor, country of cited authors, journals citing ALM, and Hirsch-index, were obtained from the Journal Citation Report and Web of Science Core Collection. Target data included ALM content in the Web of Science from January 1, 2012, to October 5, 2021. Bibliometric analysis was performed using Biblioshiny. Results: The impact factor increased from 1.481 in 2013 to 3.464 in 2020. Authors belonging to the USA, China, and Korea cited ALM articles the most. Plos One, Scientific Reports, and Frontiers in Microbiology most frequently cited ALM, besides ALM itself. The Hirsch-index was 34. The co-occurrence network of Keyword Plus indicated four clusters: diagnosis, identification, prevalence, and risk. The conceptual structure map of Keyword Plus based on multiple correspondence analysis showed two clusters: bacterial susceptibility at the bench and clinical courses. The co-citation network showed that ALM was in the cluster of the New England Journal of Medicine, The Lancet, JAMA, and the Annals of Internal Medicine. The collaboration network showed that Korean authors collaborated mainly with authors from the USA, Germany, and Italy. Conclusions: The journal’s promotion to an international top-tier journal has been successful. “Principles of transparency and best practice in scholarly publishing” and a preprint policy are yet to be added.
Brief Communication2022-01-01 Clinical Microbiology
Ki Ho Hong , M.D., Ji Won In , M.D., Jaehyeon Lee , M.D., So Yeon Kim , M.D., Kyoung Ah Lee , M.T., Seunghyun Kim , M.T., Yeoungim An , M.T., Donggeun Lee , M.T., Heungsup Sung , M.D., Jae-Seok Kim , M.D., and Hyukmin Lee , M.D.
Abstract : The sensitivity of molecular diagnostics could be affected by nucleotide variants in pathogen genes, and the sites affected by such variants should be monitored. We report a single-nucleotide variant (SNV) in the nucleocapsid (N) gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., G29179T, which impairs the diagnostic sensitivity of the Xpert Xpress SARS-CoV-2 assay (Cepheid, Sunnyvale, CA, USA). We observed significant differences between the threshold cycle (Ct) values for envelope (E) and N genes and confirmed the SNV as the cause of the differences using Sanger sequencing. This SNV, G29179T, is the most prevalent in Korea and is associated with the B.1.497 virus lineage, which is dominant in Korea. Clinical laboratories should be aware of the various SNVs in the SARS-CoV-2 genome and consider their potential effects on the diagnosis of coronavirus disease 2019.
Original Article2021-05-01 Clinical Chemistry
Hyun-Ki Kim , M.D., Hyung-Doo Park , M.D., Sang-Guk Lee , M.D., Hyojin Chae , M.D., Sang Hoon Song , M.D., Yong-Wha Lee , M.D., Yeo-Min Yun , M.D., Sunhyun Ahn , M.D., Serim Kim , M.D., Sun Min Lee , M.D., Soo-Youn Lee , M.D., and Sail Chun , M.D.; on behalf of the Clinical Mass Spectrometry Research Committee of the Korean Society of Clinical Chemistry
Abstract : Background: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is increasingly used for immunosuppressive drug tests. However, most LC-MS/MS tests are laboratory-developed and their agreement is unknown in different Korean laboratories. This interlaboratory comparison study evaluated test reproducibility and identified potential error sources. Methods: Test samples containing three concentrations of tacrolimus, sirolimus, everolimus, cyclosporine, and mycophenolic acid were prepared by pooling surplus samples from patients undergoing routine therapeutic drug monitoring and tested in duplicate in the participating 10 clinical laboratories. Reconstitution and storage experiments were conducted for the commonly used commercial calibrator set. The robust estimators of reproducibility parameters were calculated. Spearman’s rank correlation coefficient (rho, ρ) was used to evaluate the correlation between drugs. Multiple linear regression was used to determine whether the experimental conditions alter the calibration curves. Results: The reproducibility coefficient of variation exceeded 10% only for sirolimus concentrations 1 and 2 (10.8% and 12.5%, respectively) and everolimus concentrations 1 and 2 (12.3% and 11.4%, respectively). The percent difference values showed weak correlations between sirolimus and everolimus (ρ=0.334, P =0.175). The everolimus calibration curve slope was significantly altered after reconstitution following prolonged 5°C storage (P =0.015 for 14 days; P =0.025 for 28 days); the expected differences at 6 ng/mL were 0.598% for 14 days and 0.384% for 28 days. Conclusions: LC-MS/MS test reproducibility for immunosuppressive drugs seems to be good in the Korean clinical laboratories. Continuous efforts are required to achieve test standardization and harmonization, especially for sirolimus and everolimus.
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