An association between a positive direct antiglobulin test and HLA-DR12 in COVID-19.

SARS-CoV-2 infection has been reported to be associated with a positive direct antiglobulin test (DAT). In this study, an analysis of 40 consecutive coronavirus disease 2019 (COVID-19) cases from December 2020 to September 2021 in Japan revealed that patients of 70 years and over were predisposed to a positive DAT. DAT positivity was related to a decrease in the hemoglobin level. Anemia in DAT-positive COVID-19 patients was attributed to hemolysis, which was corroborated by high reticulocyte counts and an increase in the red blood cell distribution width. Human leukocyte antigen (HLA)-DRB1*12:01 and DRB1*12:02 were exclusively found in DAT-positive COVID-19 patients. In silico assays for the Spike protein of SARS-CoV-2 predicted several common core peptides that met the criteria for a B cell epitope and strong binding to both HLA-DRB1*12:01 and DRB1*12:02. Among these peptides, the amino acids sequence TSNFR, which is found within the S1 subunit of SARS-CoV-2 Spike protein, is shared by human blood group antigen Rhesus (Rh) CE polypeptides. In vitro analysis showed that the expression of HLA-DR in CD4+ T cells and CD8+ T cells from a DAT-positive patient was increased after pulsation with TSNFR-sequence-containing peptides. In summary, positive DAT is related to enhanced anemia and to HLA-DR12 in the Japanese population. A peptide sequence within SARS-CoV-2 Spike protein may act as an epitope for IgG binding to RBCs in DAT-positive COVID-19 patients.

Feasibility of the automated column agglutination technique for titration of anti-A/B antibodies in ABO-incompatible living kidney transplantation.

INTRODUCTION: Quantitative measurement of anti-A/-B antibody titers is important during ABO-incompatible living kidney transplantation (ABOi-LKT). METHODS: We conducted a multi-institutional study to measure the antibody titers using the automated column agglutination technique (auto-CAT) and tube test (TT) method in ABOi-LKT recipients. Statistical analysis was performed to evaluate the two methods. RESULTS: We examined 111 samples from 35 ABOi-LKT recipients at four institutions. The correlation coefficient of the two methods was >0.9; the concordance rate and clinically acceptable concordance rate for the IgG titers were 60.4% and 88.3%, respectively. Perioperative status did not influence the statistical significance. Parallel changes were observed in the IgG antibody titers measured using the auto-CAT or TT technique by desensitizing therapy in time-course monitoring. CONCLUSION: Auto-CAT is comparable with the TT technique and is feasible for IgG anti-A/B antibody titration in ABOi-LKT recipients.

Anti-Fya-mediated delayed hemolytic transfusion reaction following emergency-release red blood cell transfusion: possible involvement of HLA-DRB1*04:03 in the Japanese population.

A 43-year-old Japanese male, who had undergone open liver surgery for tumor resection, presented with decreased hemoglobin levels on Day 13 post-emergency-release transfusion of 16 units of Fy(a +) red blood cells. As the anemia was accompanied by increased lactate dehydrogenase, indirect bilirubin, and reticulocytes, as well as decreased haptoglobin, it was attributed to hemolysis. In the diagnostic workup for hemolytic reaction, the direct antiglobulin test result for IgG was positive and the antibody dissociated from the patient's peripheral red blood cells was identified as anti-Fya (titer, 4). The hemolytic reaction was transient (approximately 10 days), of moderate severity, and did not result in any obvious organ damage. However, a single compatible red blood cell transfusion of 2 units was required on Day 17 after the causative transfusion. Notably, HLA typing revealed that the patient carried the HLA-DRB1*04:03 allele, which has been implicated in immunogenicity and induction of anti-Fya response in Caucasian populations. In summary, this is the first documented case of definitive anti-Fya-mediated delayed hemolytic transfusion reaction associated with HLA-DRB1*04:03 in the Japanese population.

Prolonged incubation period of hepatitis B in a recipient of a nucleic acid amplification test-negative hepatitis B virus window donation.

BACKGROUND: The occurrence of transfusion-transmitted hepatitis B virus (HBV) infection has fallen dramatically due to continuous improvements in pre-transfusion laboratory testing. However, the characteristics of transfusion-transmitted HBV infection caused by individual donor nucleic acid amplification test (ID-NAT)-negative blood products are unclear. CASE PRESENTATION: A 76-year-old woman with acute myeloid leukemia was diagnosed with transfusion-transmitted HBV infection after receiving apheresis platelets derived from an ID-NAT-negative blood donation. This case was diagnosed definitively as transfusion-mediated because complete nucleotide homology of a 1556 bp region of the HBV Pol/preS1-preS2-S genes and a 23 bp region of the HBV core promoter/precore between the donor and recipient strains was confirmed by PCR-directed sequencing. The case is uncommon with respect to the unexpectedly prolonged HBV-DNA incubation period of nearly 5 months after transfusion (previously, the longest period observed since the recent implementation of ID-NAT pre-transfusion laboratory testing in Japan was 84 days). Slow-replicating HBV genotype A2 may contribute to the prolonged incubation period; also, the quantity of apheresis platelets delivered in a large volume of plasma, and/or the immune response of the recipient suffering from a hematological neoplasm, may have contributed to establishment of HBV infection in the recipient. This was supported by analysis of three previously documented cases of transfusion-transmitted HBV infection by blood products derived from ID-NAT-negative donations in Japan. CONCLUSION: Continuous monitoring of HBV infection for longer periods (>3 months) may be required after transfusion of blood components from an ID-NAT-negative HBV window donation.

Myocardial repolarization time, J-point to T-peak and T-peak to T-end intervals, have different heart rate dependency and autonomic nerve interference in healthy prepubertal children.

OBJECTIVE: The JT interval of the myocardial repolarization time can be divided into Jpoint to T-peak interval (JTp) and T-peak to T-end interval (Tpe). It is well known that the JT interval is dependent on the heart rate, but little is known regarding heart rate dependence for JTp and Tpe. The aim of the present study was to clarify the heart rate dependence of JTp and Tpe and to elucidate the interference of autonomic nervous activity with these parameters. METHODS: We evaluated 50 prepubertal children (mean age: 6.4 ± 0.5 years; male:female, 22:28) without heart disease. JTp, Tpe, and the preceding RR intervals were measured using 120 consecutive beats (lead CM5). First, the relationships between the RR interval and JTp and Tpe were evaluated by Pearson's correlation coefficient. Second, to evaluate autonomic interference with JTp and Tpe, the degree of coherence between RR interval variability and JTp or Tpe variability was calculated using spectral analysis. RESULTS: Significant positive correlations were observed between the RR interval and JTp (y = 0.116x + 105.5; r = 0.594, p < 0.001) and between the RR interval and Tpe (y = 0.037x + 44.7; r = 0.432, p < 0.001). Tpe variability had a lower degree of coherence with RR interval variability (range: 0.039-0.5 Hz) than with JTp variability (0.401 [interquartile range, 0.352-0.460] vs. 0.593 [0.503-0.664], respectively; p < 0.001). CONCLUSIONS: Tpe had lower heart rate dependence and a lower degree of autonomic nervous interference than did JTp.

Comparison of the tube test and column agglutination techniques for anti-A/-B antibody titration in healthy individuals.

BACKGROUND AND OBJECTIVES: Determination of the anti-A/-B titre pre- and post-transplantation is beneficial for treatment selection. Currently, the recommended method for antibody titration is the tube test (TT) assay. Dithiothreitol (DTT) is used for IgM antibody inactivation. Recently, a fully automated antibody titration assay using the column agglutination technique (CAT) was developed (auto-CAT). Our aim was to compare the auto-CAT and TT techniques for ABO antibody titration, to evaluate the effectiveness of DTT-treated plasma for use with auto-CAT and to define the cut-off value for antibody titration by auto-CAT. MATERIALS AND METHODS: We enrolled 30 healthy individuals, including 10 each for blood types A, B and O. We performed antibody titre measurement using the TT technique and auto-CAT simultaneously. Auto-CAT uses the bead column agglutination technology. RESULTS: With the auto-CAT cut-off value set to weak (w)+ with DTT treatment plasma, the concordance rate was 45%, and the weighted kappa value between TT and auto-CAT results was 0·994 in all subjects. Furthermore, there was a significant positive correlation between the anti-A/-B titre results obtained using the TT technique and auto-CAT in all blood types. Moreover, a positive bias (falsely elevated end-points due to agglomeration of A/B cells) was not observed in auto-CAT testing using DTT-treated plasma. CONCLUSION: Our results show that 1+ agglutination using the TT technique is equivalent to w+ agglutination obtained using auto-CAT. We recommend that DTT may be used with auto-CAT to measure antibody titres. Thus, we suggest that auto-CAT is useful for antibody titration in routine examination.

Clinical implication of LAVI over A' ratio in patients with acute coronary syndrome.

PURPOSE: The ratio of the left atrial volume index (LAVI) and late diastolic mitral annular velocity (A') is a useful echocardiographic index for identifying advanced left ventricular (LV) diastolic dysfunction in patients with dyspnoea. We investigated the clinical implications and prognostic value of the aforementioned ratio (LAVI/A') in patients with ST elevation (STE) or non-STE (NSTE) acute coronary syndrome (ACS). METHODS: We studied 212 patients with ACS. All patients underwent electrocardiography, echocardiography and measurement of plasma B-type natriuretic peptide (BNP) level on admission. The study endpoints were hospitalisation and mortality because of heart failure (HF). RESULTS: There was a significant, moderate positive correlation between LAVI/A' and natural logarithm (Ln) BNP level among the participants (r=0.48, p<0.0001). During a mean follow-up of 17 months, eight patients died and nine patients were hospitalised because of HF. The receiver operating characteristics curve indicated that LAVI/A'≥3.0 predicted these events (log-rank, p=0.0021). A significant and moderate positive correlation existed between LAVI/A' and Ln BNP level in the NSTE-ACS group (n=128; r=0.58, p<0.0001). However, the correlation between LAVI/A' and Ln BNP level was weaker in the STE-ACS group (n=84; r=0.33, p=0.0017). CONCLUSION: LAVI/A' was related to plasma BNP levels in patients with ACS, particularly in those with NSTE-ACS. This index was useful for predicting cardiac events in patients with ACS.

Beat-to-beat QT interval variability in children: normal and physiologic data.

BACKGROUND: QT interval variability provides information on ventricular vulnerability. However, QT interval variability in children has not been adequately evaluated. METHODS: One hundred seventy-three consecutive nursing infants and children (male-female, 106:67) up to school age with no intrinsic cardiac disease were included in this study, and they were categorized into 6 age-related groups. The QT variability index (QTVI) was calculated based on an electrocardiogram; and age-specific standard values, sex-specific classification, and a standard growth curve covering 0 to 7 years were constructed. RESULTS: The QTVI decreased in an age-dependent manner, reached constant values after school age, and exhibited no sex-specific differences in 6 age-related groups. CONCLUSIONS: Based on the age-dependent standardized QTVI values, it is possible to estimate the instability of ventricular repolarization in pediatric patients with better accuracy.

Difference in autonomic nervous control between ventricular septal defect and atrial septal defect based on heart rate variability.

BACKGROUND: We hypothesized that patients with atrial (ASD) and ventricular septal defects (VSD) have similarly reduced heart rate variability (HRV) since both defects cause similar increases in pulmonary blood flow and right ventricular filling pressure. We examined the correlation between HRV and respiratory frequency (RSA) characteristics and left-to-right shunt ratio (Qp/Qs) measured by Doppler echocardiography. METHODS: The study included 83 patients with diagnoses of ASD (n = 43) or VSD (n = 40). The electrocardiogram and respiratory waves were recorded during Doppler echocardiography test, and HRV was measured to calculate the low frequency (LF), high frequency (HF), total frequency (TF), and RSA components, and the LF/HF, RSA/TF, and LF/RSA ratios. Qp/Qs was calculated from Doppler echocardiography and its relationship with HRV parameters was examined by multivariate analysis. RESULTS: There was a positive correlation between Qp/Qs and LF/RSA in the ASD group, and a negative correlation in the VSD group. In contrast, Qp/Qs correlated negatively with RSA/TF in the ASD group, and positively in the VSD group. CONCLUSION: Different effects of respiratory vagal activity on HRV were observed in patients with ASD versus VSD.

Autonomic modulation of sinus and atrioventricular nodes in premature low-birth-weight infants.

Respiratory vagal activity is expressed by heart rate variability (HRV) at approximately 1 month of age in premature low-birth-weight infants (PLBWI). However, the autonomic inputs into the sinus node (SAN) and atrioventricular node (AVN) in PLBWI are unclear. We evaluated the variability in PP and PR intervals at day zero (day 0) and 1 month (1 month) after birth in 16 PLBWI (gestation 32.3 +/- 1.3 weeks, birth weight 1.578 +/- 257 g). The polygraph was recorded during sleep on day 0 and at 1 month. PP and PR intervals and the number of respiratory cycles were measured, and frequency analysis was performed by auto-correlation fast Fourier transforms. Power spectral density (PSD: ms(2)) was calculated for the low frequency domain (LF: 0.036 approximately 0.146 Hz), high frequency domain (HF: 0.146 approximately 0.390 Hz), total frequency (TF: 0.036 approximately 2.000 Hz), and respiratory sinus arrhythmia (RSA: frequency bandwidth of 0.3 Hz with peak respiratory frequency as median), and the PSD ratio in the PP and PR intervals (LF/HF, RSA/TF) were compared. Compared with day 0, a decrease in the LF/HF ratio and an increase in the RSA/TF ratio in PP intervals were observed at 1 month, consistent with expression of respiratory vagal activity. For PR intervals, on the other hand, the LF/HF ratio increased, indicative of accentuated sympathetic activity. However, the respiratory vagal input was weak, and the RSA/TF ratio remained unchanged. These observations suggest that, in PLBWI at 1 month, AVN conduction was not predominatly influenced by respiratory-related vagal activity, but was controlled by autonomic regulation, independent of the SAN.

Correlation of PP and PR intervals in premature low birth weight infants.

We examined the developmental change by which autonomic neural activity associated respiration modulates spontaneous firing rate of sinus (SA) node and atrioventricular (AV) conduction in premature infants born with low birth weight (LBWI). The purpose of this study was to clarify whether variation of PR is correlated with that of PP or those are independent in LBWI with immature autonomic nervous system. We investigated, therefore, whether there are spontaneous functional differences in the innervation of SA and AV nodes. Further, we evaluated the maturation of autonomic nervous system progressing in the period, on the day of birth (Day 0) to approximately one month after the birth (Month 1). This study was performed in thirteen LBWI during deep sleep. EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0 and Month 1. Then, the data were analyzed as follows: 1) correlations among the means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP and PR intervals by Lorenz plot analysis method, 3) correlation analysis among PP, PR and RR intervals by linear regression method and 4) frequency analysis for PP and PR intervals by high-speed Fourier transform method (FFT) and determination of frequency density. The PP interval decreased as growing in the period. Contrary PR interval increased. In LBWI, the automatic nervous activities including parasympathetic nerve activity for spontaneous firing cycle of SA node and ventricular excitation cycle on Month 1 were higher than Day 0. It was assumed that the vagal nerve activity for the AV conduction was enhanced. However, there was no significant change in linear regression slope for the spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF changes for PP and PR obtained by frequency analysis, were opposite. Therefore, it was suggested that the maturity of autonomic nervous system progresses in the period, Day 0 to approximately Month 1, but the variations in PP and PR are independent each other.