Review Article2021-01-01
Diagnostic Immunology

Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases

Nobuharu Tamaki , M.D., Ph.D., Masayuki Kurosaki , M.D., Ph.D., Rohit Loomba , M.D., M.H.S., and Namiki Izumi , M.D., Ph.D.

Ann Lab Med 2021; 41(1): 16-24

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Abstract : An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.

Brief Communication2022-01-01
Diagnostic Immunology

Clinical Evaluation of the Rapid STANDARD Q COVID-19 Ag Test for the Screening of Severe Acute Respiratory Syndrome Coronavirus 2

Hyung Woo Kim , M.D., Mikyoung Park , M.D., Ph.D., and Jong Ho Lee , M.D.

Ann Lab Med 2022; 42(1): 100-104

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Abstract : Standard tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detect the presence of viral RNA using real-time reverse transcription (rRT)-PCR. Recently, convenient, rapid, and relatively inexpensive SARS-CoV-2 antigen (Ag) detection methods have been developed. The STANDARD Q COVID-19 Ag test (SD Biosensor, Inc., Suwon, Korea) is a rapid immunochromatography test that qualitatively detects the nucleocapsid protein of SARS-CoV-2 using gold conjugated antibodies. We evaluated its performance in comparison with that of Allplex 2019-nCoV Assay (Seegene, Seoul, Korea) in a retrospective case-control study using residual samples. The sensitivity and specificity of the STANDARD Q COVID-19 Ag test were 89.2% (58/65) and 96.0% (96/100), respectively. Cycle threshold (Ct) values for the three target SARS-CoV-2 genes (envelope, RNA-dependent RNA polymerase, and nucleocapsid genes) included in Allplex 2019-nCoV Assay were significantly lower in Ag test-positive patients than in Ag test-negative patients (P

Original Article2021-11-01
Diagnostic Immunology

Combination of a SARS-CoV-2 IgG Assay and RT-PCR for Improved COVID-19 Diagnosis

Kotaro Aoki , Ph.D., Kunitomo Takai , M.H.E.S., Tatsuya Nagasawa , M.M.S., Katsuhito Kashiwagi , M.D., Nobuaki Mori , M.D., Ph.D., Keiji Matsubayashi , M.S., Masahiro Satake , M.D., Ph.D., Ippei Tanaka , Ph.D., Nanae Kodama , M.S., Takahiro Shimodaira , M.M.S, Yoshikazu Ishii , Ph.D., Taito Miyazaki , M.D., Toshiaki Ishii , M.M.S, Toshisuke Morita , M.D., Ph.D., Toru Yoshimura , Ph.D., and Kazuhiro Tateda , M.D., Ph.D.

Ann Lab Med 2021; 41(6): 568-576

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Abstract : Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is generally diagnosed by reverse transcription (RT)-PCR or serological assays. The SARS-CoV-2 viral load decreases a few days after symptom onset. Thus, the RT-PCR sensitivity peaks at three days after symptom onset (approximately 80%). We evaluated the performance of the ARCHITECT^® SARS-CoV-2 IgG assay (henceforth termed IgG assay; Abbott Laboratories, Lake County, IL, USA), and the combination of RT-PCR and the IgG assay for COVID-19 diagnosis. Methods: In this retrospective study, 206 samples from 70 COVID-19 cases at two hospitals in Tokyo that were positive using RT-PCR were used to analyze the diagnostic sensitivity. RT-PCR-negative (N=166), COVID-19-unrelated (N=418), and Japanese Red Cross Society (N=100) samples were used to evaluate specificity. Results: Sensitivity increased daily after symptom onset and exceeded 84.4% after 10 days. Specificity ranged from 98.2% to 100% for samples from the three case groups. Seroconversion was confirmed from 9 to 20 days after symptom onset in 18 out of 32 COVID-19 cases with multiple samples and from another case with a positive result in the IgG assay for the first available sample. Conclusions: The combination of RT-PCR and IgG assay improves the robustness of laboratory diagnostics by compensating for the limitations of each method.

Original Article2022-01-01
Diagnostic Immunology

Performance Comparison of Five SARS-CoV-2 Antibody Assays for Seroprevalence Studies

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.

Ann Lab Med 2022; 42(1): 71-78

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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.

Brief Communication2021-07-01
Diagnostic Immunology

Causes of Positive Pretransplant Crossmatches in the Absence of Donor-Specific Anti-Human Leukocyte Antigen Antibodies: A Single-Center Experience

Hyunhye Kang , M.D., Jaeeun Yoo , M.D., Sang-Yoon Lee , M.T., and Eun-Jee Oh , M.D., Ph.D.

Ann Lab Med 2021; 41(4): 429-435

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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

Association of HLA-DRB1 and -DQB1 Alleles with Susceptibility to IgA Nephropathy in Korean Patients

Ji Won In , M.D., Kiwook Jung , M.D., Sue Shin , M.D., Ph.D., Kyoung Un Park , M.D., Ph.D., Hajeong Lee , M.D., Ph.D., and Eun Young Song , M.D., Ph.D.

Ann Lab Med 2022; 42(1): 54-62

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Abstract : Background: Associations between IgA nephropathy (IgAN) and HLA-DRB1 and -DQB1 alleles have been reported in several ethnic groups. We investigated the association of HLA-DRB1 and -DQB1 alleles with the predisposition for IgAN and disease progression to end-stage kidney disease (ESKD) in Korean patients. Methods: We analyzed HLA-DRB1 and -DQB1 genotypes in 399 IgAN patients between January 2000 and January 2019 using a LIFECODES sequence-specific oligonucleotide (SSO) typing kit (Immucor, Stamford, CT, USA) or a LABType SSO Typing Test (One Lambda, Canoga Park, CA, USA). Alleles with a significant difference in two-digit resolution were further analyzed using in-house sequence-based typing and sequence-specific primer PCR. As controls, 613 healthy hematopoietic stem cell donors were included. Kidney survival was analyzed in 281 IgAN patients with available clinical and laboratory data using Cox regression analysis. Where needed, P-values were adjusted using Bonferroni correction. Results: The allele frequencies of HLA-DRB1*04:05 (corrected P [Pc]

Original Article2022-01-01
Diagnostic Immunology

Comparison of the Automated Fluorescent Immunoassay System With Roche Elecsys and Beckman Coulter Access 2 Assays for Anti-Müllerian Hormone Measurement

Aera Han , M.D., Ph.D., Borum Suh , M.D., Gwang Yi , M.D., Yoo Jin Lee , M.D., and Sung Eun Kim , M.D.

Ann Lab Med 2022; 42(1): 47-53

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Abstract : Background: Since 2017, automated assays have been used in most clinical laboratories for anti-Müllerian hormone (AMH) level measurement. We evaluated the analytical performance of the newly developed automated fluorescent immunoassay system (AFIAS) AMH assay (Boditech Med, Gangwon-do, Korea) in comparison with the Roche Elecsys and Beckman Coulter Access 2 AMH assays. Methods: Analytical performance of the AFIAS AMH assay was assessed in terms of linearity, repeatability, and within-laboratory precision (CV%) using human recombinant AMH samples according to the Clinical and Laboratory Standards Institute (CLSI) guidelines EP05 and EP06. Using 293 serum samples collected from an infertility clinic, the AMH levels were compared across AFIAS, Elecsys, and Access 2 AMH assays according to the CLSI EP09 guidelines. Results: The AFIAS AMH assay results were linear across the measurement range of 0.420–72.386 pmol/L AMH, with repeatability of 6.341%. CV% of the AFIAS AMH assay for three levels of control, 1.786, 7.143, and 56.857 pmol/L, were 5.801%, 5.714%, and 6.228%, respectively. The results of the three AMH assays showed strong correlation: AFIAS and Elecsys [slope, 1.055 (95% confidence interval (CI), 1.022–1.088) and Spearman’s rho, 0.978 (95% CI, 0.973–0.983)], Elecsys and Access 2 [slope, 0.813 (95% CI, 0.791–0.834) and Spearman’s rho, 0.986 (95% CI, 0.983–0.989)], and AFIAS and Access 2 [slope, 0.836 (95% CI, 0.821–0.853) and Spearman’s rho, 0.984 (95% CI, 0.980–0.988)]. Conclusions: The AFIAS AMH assay may be an alternative to the Roche Elecsys and Beckman Coulter Access 2 AMH assays.

Original Article2021-03-01
Diagnostic Immunology

Prediction of HLA-DQ in Deceased Donors and its Clinical Significance in Kidney Transplantation

Soo-Kyung Kim , M.D., Ph.D., John Jeongseok Yang , M.D., Sang-Hyun Hwang , M.D., Ph.D., Heungsup Sung , M.D., Ph.D., Sung Shin , M.D., Ph.D., Sun-Young Ko , M.D., Ph.D., and Heung-Bum Oh , M.D., Ph.D.

Ann Lab Med 2021; 41(2): 190-197

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Abstract : Background: HLA-DQ typing in deceased donors is not mandatory in Korea. Therefore, when patients develop DQ antibodies after kidney transplantation (KT) from deceased donor, it is impossible to determine whether they are donor-specific antibodies (DSA). We developed DQ prediction programs for the HLA gene and evaluated their clinical utility. Methods: Two HLA-DQ prediction programs were developed: one based on Lewontin’s linkage disequilibrium (LD) and haplotype frequency and the other on an artificial neural network (ANN). Low-resolution HLA-A, -B, -DR, and -DQ typing data of 5,603 Korean patients were analyzed in terms of haplotype frequency and used to develop an ANN DQ prediction program. Predicted DQ (pDQ) genotype accuracy was analyzed using the typed DQ data of 403 patients. pDQ DSA agreement, sensitivity, specificity, and false-negative rate was evaluated using 1,970 single-antigen bead assays performed on 885 KT recipients. The clinical significance of DQ and pDQ DSA was evaluated in 411 KT recipients. Results: pDQ genotype accuracies were 75.4% (LD algorithm) and 75.7% (ANN). When the second most likely pDQ (LD algorithm) was also considered, the genotype accuracy increased to 92.6%. pDQ DSA (LD algorithm) agreement, sensitivity, specificity, and false-negative rate were 97.5%, 97.3%, 98.6%, and 2.4%, respectively. The antibody-mediated rejection treatment frequency was significantly higher in DQ or pDQ DSA-positive patients than in DQ or pDQ DSA-negative patients (P<0.001). Conclusions: Our DQ prediction programs showed good accuracy and could aid DQ DSA detection in patients who had undergone deceased donor KT without donor HLA-DQ typing.

Original Article2021-03-01
Diagnostic Immunology

Relationship Between Rotavirus P[6] Infection in Korean Neonates and Histo-Blood Group Antigen: a Single-Center Study

Su-Kyung Lee , M.S., Su Jin Oh , M.S., Seoheui Choi , M.D., Soo Han Choi , M.D., Seon-Hee Shin , M.D., Eun Jin Lee , M.D., Eun-Jung Cho , M.D., Jungwon Hyun , M.D., Hyun Soo Kim , M.D.

Ann Lab Med 2021; 41(2): 181-189

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Abstract : Background: Rotaviruses are a major cause of pediatric gastroenteritis. The rotavirus P[6] genotype is the most prevalent genotype isolated from Korean neonates but has rarely been reported in other countries. Histo-blood group antigen (HBGA) is known to play an important role in rotavirus infection. We investigated the relationship between rotavirus genotype and HBGA-Lewis blood type in Korean children and explored the reasons for the predominance of rotavirus P[6] strain in Korean neonates. Methods: Blood and stool samples were collected from 16 rotavirus-infected patients. Rotavirus G (VP7) and P (VP4) genotyping was performed using reverse transcription-PCR and sequencing. Lewis antigen phenotypes (Le^a/Le^b) were tested, and HBGA-Lewis genotype was determined by sequencing the secretor (FUT2) and Lewis (FUT3) genes. Deduced amino acid sequences and three-dimensional structures of the VP8* portion of the rotavirus VP4 protein were analyzed. Results: All P[6] rotaviruses were isolated from neonates under one month of age, who were negative or weakly positive for the Le^b antigen. However, 10 of the 11 non-P[6] rotaviruses were isolated from older children who were Le^b antigen-positive. The VP8* amino acid sequences differed among P[6], P[4], and P[8] genotypes. Korean P[6] strains showed a unique VP8* sequence with amino acid substitutions, including Y169>L169, which differed from the sequences of P[6] strains from other countries. Conclusions: The predominance of the rotavirus P[6] genotype in Korean neonates may be related to the interaction between HBGA-Lewis antigen and the VP8* portion of the VP4 protein, and this information will be helpful in future neonatal vaccine development.

Letter to the Editor2022-03-01
Diagnostic Immunology

Clinical Significance of Elevated Serum Caspase-1 Levels in Patients With Ankylosing Spondylitis

Sang-Hyon Kim , M.D., Ph.D., Ji-Hyun Lee , M.S., Hye-Jin Jeong , M.D., Ji-Min Kim , M.D., Ph.D., Won-Ki Baek , M.D., Ph.D., Tae-Hwan Kim , M.D., Ph.D., Jae-Bum Jun , M.D., Ph.D., and Chang-Nam Son , M.D., Ph.D.

Ann Lab Med 2022; 42(2): 293-295

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