Most Read (Last 3 years)

  • Brief Communication2023-01-01 Diagnostic Immunology

    Establishment of Reference Intervals of Cytokeratin 19 Fragment Antigen 21-1 in Korean Adults

    Sumi Yoon , M.D., Ph.D., Yong Kwan Lim , M.D., Hye Ryoun Kim , M.D., Ph.D., Mi-Kyung Lee , M.D., Ph.D., and Oh Joo Kweon , M.D., Ph.D.

    Ann Lab Med 2023; 43(1): 82-85

    Abstract : Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is useful for predicting and monitoring non-small cell lung cancer prognosis. We established reference intervals (RIs) of CYFRA 21-1 in Korean adults, including those older than 60 years. Data of 4,098 apparently healthy subjects (age range, 20–87 years) were analyzed after excluding those with a history of malignancy, high tumor marker concentrations (except CYFRA 21-1), and/or abnormal findings on a chest computed tomography scan through medical chart review. After removing two outliers, RIs of CYFRA 21-1 were determined using data of 4,096 subjects based on the non-parametric method (2.5th and 97.5th percentiles) according to CLSI guidelines EP28-A3c. The subjects were divided into two and four groups according to sex and age (20–40, 41–50, 51–60, and >60 years), respectively, and the median CYFRA 21-1 concentration was compared between the groups. The RI of CYFRA 21-1 was 0.66–3.84 ng/mL, applicable to both men and women. Regardless of sex, the CYFRA 21-1 concentration increased with age, suggesting that age-dependent RIs of CYFRA 21-1 should be applied. Rather than using a single RI provided by the manufacturer, the RI of CYFRA 21-1 should be continually verified and established in each clinical laboratory.

  • Original Article2023-07-01 Diagnostic Immunology

    Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients

    Haeun Lee , M.D., Hanbi Lee , M.D., Sang Hun Eum , M.D., Eun Jeong Ko , M.D., Ph.D., Ji-Won Min , M.D., Ph.D., Eun-Jee Oh , M.D., Ph.D., Chul Woo Yang , M.D., Ph.D., and Byung Ha Chung , M.D., Ph.D.

    Ann Lab Med 2023; 43(4): 364-374

    Abstract : Background: The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. Methods: We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary’s Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. Results: The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79–51.56) than in LDKT (OR: 3.76, 95% CI: 0.99–14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. Conclusions: Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.

  • Original Article2024-01-01 Diagnostic Immunology

    Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients

    Ahram Han , M.D., Sangil Min , M.D., Ph.D., Eun-Ah Jo , M.D., Hajeong Lee , M.D., Ph.D., Yong Chul Kim , M.D., Ph.D., Seung Seok Han , M.D., Ph.D., Hee Gyung Kang , M.D., Ph.D., Yo Han Ahn , M.D., Ph.D., Inseong Oh , M.D., Eun Young Song , M.D., Ph.D., and Jongwon Ha , M.D., Ph.D.

    Ann Lab Med 2024; 44(1): 64-73

    Abstract : Background: Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients. Methods: In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded. Results: After the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range [IQR] 7.2–402.8) to 1,612.1 (IQR 153.9–5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels (

  • Original Article2023-09-01 Diagnostic Immunology

    Clinical Significance of Serum IgG4 in the Diagnosis and Treatment Response of IgG4-Related Disease in Adults of Southwest China: A Retrospective Study

    Bin Wei , M.M., Ying Guo , M.M., Xiaoqi Ou , B.M., Liyan Lin , M.M., Zhenzhen Su , M.M., Lixin Li , B.M., XiaoJuan Wu , M.D., and Bei Cai , M.D.

    Ann Lab Med 2023; 43(5): 461-469

    Abstract : Background: There is no standard cut-off value of serum IgG4 concentration and serum IgG4/total IgG ratio for the diagnosis of IgG4-related disease (IgG4-RD) or as a marker of treatment responses. We aimed to explore this issue through a retrospective cohort analysis of adults in southwest China. Methods: The diagnostic performance of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD was evaluated in a retrospective analysis of 177 adults newly diagnosed as having IgG4-RD and 877 adults without IgG4-RD. Dynamic analysis was performed to evaluate the significance of serum IgG4 concentration on IgG4-RD treatment responses. Results: The serum IgG4 concentration differed according to sex. The optimal cut-off values of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD diagnosis were 1.92 g/L and 0.12 in males and 1.83 g/L and 0.11 in females, respectively. For patients with serum IgG4 concentration >2.01 g/L, the cut-off values in the total population were >3.00 g/L and 0.19, respectively. The median serum IgG4 concentration decreased over time, and the decrease rate increased over time. The serum IgG4 concentration significantly decreased at >1 week post-treatment (P=0.004), and the median decrease rate was close to 50% at >4 weeks post-treatment. Conclusions: Serum IgG4 can be a good indicator for IgG4-RD diagnosis; however, different diagnostic cut-off values should be determined according to sex. The decreasing rate is more conducive than the serum IgG4 concentration to monitor treatment efficacy. The IgG4/IgG ratio did not improve the diagnostic efficacy for IgG4-RD.

  • Original Article2023-01-01 Diagnostic Immunology

    Indirect Method for Estimation of Reference Intervals of Inflammatory Markers

    Taewon Kang , B.S., Jeaeun Yoo , M.D., Dong Wook Jekarl , M.D., Hyojin Chae , M.D., Myungshin Kim , M.D., Yeon-Joon Park , M.D., Eun-Jee Oh , M.D., and Yonggoo Kim , M.D.

    Ann Lab Med 2023; 43(1): 55-63

    Abstract : Background: The direct method for reference interval (RI) estimating is limited due to the requirement of resources, difficulties in defining a non-diseased population, or ethical problems in obtaining samples. We estimated the RI for inflammatory biomarkers using an indirect method (RII). Methods: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and presepsin (PSEP) data of patients visiting a single hospital were retrieved from April 2009 to April 2021. Right-skewed data were transformed using the Box-Cox transformation method. A mixed population of non-diseased and diseased distributions was assumed, followed by latent profile analysis for the two classes. The intersection point of the distribution curve was estimated as the RI. The influence of measurement size was evaluated as the ratio of abnormal values and adjustment (n×bandwidth) of the distribution curve. Results: The RIs estimated by the proposed RII method (existing method) were as follows: CRP, 0–4.1 (0–4.7) mg/L; ESR, 0–10.2 (0–15) mm/hr and PSEP, 0–411 (0–300) pg/mL. Measurement sizes ≥2,500 showed stable results. An abnormal-to-normal value ratio of 0.5 showed the most accurate result for CRP. Adjustment values ≤5 or >5 were applicable for a measurement size

  • Original Article2023-05-01 Diagnostic Immunology

    Collaborative Study to Establish National Reference Standards for Anti-HIV-1 Antibody

    Hee Jin Huh , M.D., Soo-Kyung Kim , M.D., Jae-Woo Chung , M.D., Soo Jin Yoo , M.D., Kyoung Ho Roh , M.D., Seok Lae Chae , M.D., and Young Joo Cha , M.D.

    Ann Lab Med 2023; 43(3): 273-279

    Abstract : Background: National reference standards for anti-HIV-1 antibody are needed to evaluate the performance and maintain the quality control of anti-HIV-1 antibody assays. The aim of this study was to prepare a mixed-titer performance panel and assess its suitability as a national reference standard for anti-HIV-1 antibody according to stability, collaboration, and other studies. Methods: Nineteen serum samples from different HIV patients were obtained, along with 15 units of fresh frozen plasma samples with negative anti-HIV-1 antibody results. Ten anti-HIV-1 antibody-positive candidate standards and two negative candidate standards were prepared based on the reactivity in the Alinity i HIV Ag/Ab combo assay (Abbott Laboratories, Wiesbaden, Germany). A collaborative study was conducted across eight laboratories using five anti-HIV-1 antibody assays. Real-time and accelerated stability were evaluated to assess the long-term stability. Results: In the collaborative study, results of all five anti-HIV-1 antibody assays were positive for all 10 candidate standards prepared using HIV patient samples. The CV of each assay for every candidate standard was within 10%, except for one assay result. No real-time and accelerated stability change trend was observed at −70°C or −20°C, supporting that the reference standards were maintained in a stable state at −70°C for long-term storage. Conclusions: The overall results suggest that the 12 candidate standards could serve as national reference standards for anti-HIV-1 antibody.

  • Original Article2023-11-01 Diagnostic Immunology

    Comparison of Four T-cell Assays and Two Binding Antibody Assays in SARS-CoV-2 Vaccinees With or Without Omicron Breakthrough Infection

    Yeon Ju Seo , M.D., Inseong Oh , M.D., Minjeong Nam , M.D., Ph.D., Sue Shin , M.D., Ph.D., Eun Youn Roh , M.D., Ph.D., and Eun Young Song , M.D., Ph.D.

    Ann Lab Med 2023; 43(6): 596-604

    Abstract : Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann–Whitney U, Wilcoxon signed-rank, and Spearman’s correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60–0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33–0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43–0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions: T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.

  • Brief Communication2022-11-01 Diagnostic Immunology

    Immunogenicity of Third-dose BNT162b2 mRNA Vaccine Following Two Doses of ChAdOx1 in Health Care Workers: A Prospective Longitudinal Study

    Jung-Ah Kim , M.D., Hae In Bang , M.D., Jeong Won Shin , M.D., Ph.D., Yoonhye Park , M.T., Saerom Kim , M.T., Mi-Young Kim , M.T., Eui Young Jang , M.T., Woo Yong Shin , M.D., Jieun Kim , M.D., Ph.D., Rojin Park , M.D., Ph.D., and Tae Youn Choi , M.D., Ph.D.

    Ann Lab Med 2022; 42(6): 688-692

    Abstract : Following the original severe acute respiratory syndrome coronavirus 2 strain (Wuhan-Hu-1) in December 2019, the Delta variant in May 2021 and the Omicron variant in December 2021 were classified as variants of concern. The pandemic has been ongoing for more than two years, and the three-dose vaccination rate has reached approximately 50% in Korea. We analyzed anti-S antibodies (Abs) and neutralizing Abs (NAbs) in 32 healthcare workers at a university hospital, focusing on the first to third doses of ChAdOx1-ChAdOx1-BNT162b2, which is the most common vaccination regimen in Korea. Antibodies were analyzed at eight time points according to the vaccine regimen. The first to third doses of ChAdOx1-ChAdOx1-BNT162b2 produced high Ab concentrations; NAb concentrations after the third dose were predicted to remain high for a longer period than those after the first and second doses. The effectiveness of a second dose of ChAdOx1 in the real world was demonstrated by analyzing samples collected during an outbreak that occurred in the study period, 4–5 months after the second dose. The relative risk ratio was 88.0%, and the efficacy of the second ChAdOx1 dose was 12.0% (P

  • Original Article2024-01-01 Diagnostic Immunology

    Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders

    Jin Myoung Seok , M.D., Patrick Waters , Ph.D., Mi Young Jeon , Hye Lim Lee , M.D., Ph.D., Seol-Hee Baek , M.D., Ph.D., Jin-Sung Park , M.D., Ph.D., Sa-Yoon Kang , M.D., Ohyun Kwon , M.D., Jeeyoung Oh , M.D., Ph.D., Byung-Jo Kim , M.D., Ph.D., Kyung-Ah Park , M.D., Ph.D., Sei Yeul Oh , M.D., Ph.D., Byoung Joon Kim , M.D., Ph.D., and Ju-Hong Min , M.D., Ph.D.

    Ann Lab Med 2024; 44(1): 56-63

    Abstract : Background: The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics. Methods: We established the CBA using HEK 293 cells transiently overexpressing full-length human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD). Results: Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ=0.883, P

  • Original Article2023-09-01 Diagnostic Immunology

    Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients

    Georgios Lioulios , Ph.D., Asimina Fylaktou , Ph.D., Despina Asouchidou , Ph.D., Aliki Xochelli , Ph.D., Vasiliki Nikolaidou , M.Sc., Stamatia Stai , M.Sc., Michalis Christodoulou , M.Sc., Panagiotis Giamalis , Ph.D., Ioannis Tsouchnikas , Ph.D., Aikaterini Papagianni , M.D., Ph.D., and Maria Stangou , M.D., Ph.D.

    Ann Lab Med 2023; 43(5): 451-460

    Abstract : Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at Τ1 to 53.7% at Τ3. Age was negatively correlated to the NAb titer at T1 and Τ2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.

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Annals of Laboratory Medicine
Journal Information September, 2024
Vol.44 No.5
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