Attenuated humoral response against SARS-CoV-2 mRNA vaccination in allogeneic stem cell transplantation recipients.

Antibody persistence several months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS-CoV-2 S1 Ab became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1235.4 arbitrary units (AU)/ml. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with Ab titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤1 year, history of clinically significant CMV infection, and use of >5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/ml, and use of >5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and CMV infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, Ab titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately.

Archival bone marrow smears are useful in targeted next-generation sequencing for diagnosing myeloid neoplasms.

Gene abnormalities, including mutations and fusions, are important determinants in the molecular diagnosis of myeloid neoplasms. The use of bone marrow (BM) smears as a source of DNA and RNA for next-generation sequencing (NGS) enables molecular diagnosis to be done with small amounts of bone marrow and is especially useful for patients without stocked cells, DNA or RNA. The present study aimed to analyze the quality of DNA and RNA derived from smear samples and the utility of NGS for diagnosing myeloid neoplasms. Targeted DNA sequencing using paired BM cells and smears yielded sequencing data of adequate quality for variant calling. The detected variants were analyzed using the bioinformatics approach to detect mutations reliably and increase sensitivity. Noise deriving from variants with extremely low variant allele frequency (VAF) was detected in smear sample data and removed by filtering. Consequently, various driver gene mutations were detected across a wide range of allele frequencies in patients with myeloid neoplasms. Moreover, targeted RNA sequencing successfully detected fusion genes using smear-derived, very low-quality RNA, even in a patient with a normal karyotype. These findings demonstrated that smear samples can be used for clinical molecular diagnosis with adequate noise-reduction methods even if the DNA and RNA quality is inferior.

Effects of a 21 day metabolic study on serum opsonic activity in female college students, assessed by a chemiluminescence technique.

A metabolic study to evaluate nutritional balance, in which subjects have to eat all the foods supplied and maintain a set schedule, is thought to be stressful for the subjects. The effects of stress on the immune system have been studied extensively. However, there are no studies of non-specific immunological changes during a metabolic study. Serum opsonic activity (SOA) is a direct and suitable indicator of non-specific humoral immunity. In this study, we used luminol-dependent chemiluminescence (LmCL) to measure reactive oxygen species (ROS) generation from pooled human neutrophils as an indicator of SOA. We also measured serum immunoglobulin levels and plasma myeloperoxidase (MPO) activity. Eleven female college students took part in this 21 day metabolic study after giving their written informed consent. The results obtained suggest that the metabolic study has almost no effect on immunoglobulin levels. According to MPO levels, neutrophils in vivo may be deactivated to some minor extent. In contrast to these results, peak time (PT) and peak height (PH) of LmCL were changed significantly during the metabolic study. In conclusion, SOA increased during the 21 day metabolic study. There was no significant correlation between SOA and serum immunoglobulin levels on any of the study days.