Advancing Precise Syphilis Diagnosis: A Nontreponemal IgM Antibody-Based Model for Latent Syphilis Staging.

Purpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies. Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer-Lemeshow χ2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model's stability. Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer-Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model's robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer-Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model. Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

Treponema pallidum recombinant protein Tp47 activates NOD-like receptor family protein 3 inflammasomes in macrophages via glycolysis.

Glycolysis is a key pathway in cellular glucose metabolism for energy supply and regulates immune cell activation. Whether glycolysis is involved in the activation of NOD-like receptor family protein 3 (NLRP3) inflammasomes during Treponema pallidum (T. pallidum) infection is unclear. In this study, the effect of T. pallidum membrane protein Tp47 on NLRP3 inflammasome activation in rabbit peritoneal macrophages was analysed and the role of glycolysis in NLRP3 inflammasome activation was explored. The results showed that Tp47 promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, enhanced glycolysis and glycolytic capacity of macrophage, and promoted the production of macrophage glycolytic metabolites citrate, phosphoenolpyruvate, and lactate. The M2 pyruvate kinase (PKM2) inhibitor shikonin down-regulated the Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, and suppressed the Tp47-enhanced glycolysis and glycolytic capacity. Similarly, si-PKM2 significantly inhibited Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression and the Tp47-enhanced glycolysis and glycolytic capacity in macrophages. In conclusion, Tp47 activated NLRP3 inflammasomes via PKM2-dependent glycolysis and provided a new perspective on the effect of T. pallidum infection on host macrophages, which would contribute to the understanding of the infection mechanism and host immune mechanism of T. pallidum.

Treponema pallidum Promotes the Polarization of M2 Subtype Macrophages to M1 Subtype Mediating the Apoptosis and Inhibiting the Angiogenesis of Human Umbilical Vein Endothelial Cells.

M2 macrophages were related to local immune homeostasis and maternal-fetal tolerance in normal pregnancy; whether M2 macrophages can respond to the stimulation of Treponema pallidum to mediate placental vascular inflammation injury is unclear. In this study, M2 macrophages were constructed to investigate the impact of T. pallidum on macrophage polarization and the underlying signaling pathway involved in this process, and the influence of macrophage polarization triggered by T. pallidum on the apoptosis and angiogenesis of human umbilical vein endothelial cells (HUVEC) was also explored. The results showed that M2 macrophage markers (CD206 and PPARγ) and anti-inflammatory factors (TGFß and CCL18) were decreased, while M1 macrophage marker CD80 and inflammatory cytokines (IL1ß and TNFα) were increased when M2 macrophages were treated with T. pallidum, indicating that T. pallidum promoted the polarization of M2 subtype macrophages to the M1 subtype. Moreover, T. pallidum-induced M1 macrophage polarization was found to be significantly correlated with the activation of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1). In addition, T. pallidum-induced M1 macrophages were found to promote apoptosis and inhibit the angiogenesis of HUVECs, and JAK1 or STAT1 inhibitors could weaken the apoptosis rate and promote the angiogenesis of HUVECs. These findings revealed that T. pallidum promoted the polarization of M2 macrophages to the M1 subtype through the JAK1-STAT1 signal pathway mediating the apoptosis and inhibiting angiogenesis of HUVECs, which may provide a possible mechanism for T. pallidum-induced adverse pregnancy outcomes.

Screening the B- and T-cell epitope map of TP0136 and exploring their effect in a Treponema pallidum rabbit model.

The systemic immune response, including B- and T-cell reactions, plays a corresponding role in syphilis infections. The TP0136 protein is a target of the immune response in infected hosts and may mediate the immune response. Here, we developed a method that combining reverse vaccine approach with Pepscan/T-cell proliferation to screen and identify three B-cell and two T-cell epitopes of TP0136, and explore the role of the B- and T-cell epitopes in immunized-infected animals. The results showed that immunized with B-cell epitopes not only had no protective effect but also aggravated the syphilitic lesion development. While immunized with T-cell epitopes of TP0136 could induce a strong Th1-cellular immunity response, which could attenuate syphilitic lesion development to a certain extent. The variation in exacerbation or attenuation of skin lesions, induced by distinct B- and T-cell epitopes of Tp0136, within the host's defense against syphilis warrants in-depth exploration.

Response and duration of serum anti-SARS-CoV-2 antibodies induced by the third dose of an inactivated vaccine: A prospective longitudinal cohort study at 21 serial time points over 641 days.

Given the prevalence of low-pathogenic but highly infectious Omicron variants, a cohort study was conducted to assess the response and duration of novel coronavirus-inactivated vaccine-induced antibodies 1 year after the third dose (Day 641). Blood samples were collected and anti-spike neutralizing antibodies (neutralizing antibody), total antibodies against the receptor-binding domain of the spike protein (total antibody), and immunoglobulin G antibodies against the spike protein (IgG antibody) were determined. Antibody kinetics and attenuation were evaluated. The results showed that the levels of neutralizing, total, and IgG antibodies on Day 641 were 98.05 IU/mL, 152.8 AU/mL, and 7.68 S/CO, respectively. Levels of anti-SARS-CoV-2 antibodies were higher in the younger subgroup than in the older subgroup at several time points after the second and third doses. The seropositive rate of neutralizing antibodies providing protection from infection or severe infection was 46.87% and 87.5%, and the seropositive rates of total antibody and IgG antibody were maintained at 100% and 90.63%, respectively. The half-lives of neutralizing, total, and IgG antibodies were 186.89, 363.04, and 417.50 days, respectively. Collectively, anti-SARS-CoV-2 antibodies may provide a certain degree of protection from infection 1 year after the third dose and high protection from severe infection.

Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma.

Glioblastomas are highly heterogeneous brain tumors. Despite the availability of standard treatment for glioblastoma multiforme (GBM), i.e., Stupp protocol, which involves surgical resection followed by radiotherapy and chemotherapy, glioblastoma remains refractory to treatment and recurrence is inevitable. Moreover, the biology of recurrent glioblastoma remains unclear. Increasing evidence has shown that intratumoral heterogeneity and the tumor microenvironment contribute to therapeutic resistance. However, the interaction between intracellular heterogeneity and drug resistance in recurrent GBMs remains controversial. The aim of this study was to map the transcriptome landscape of cancer cells and the tumor heterogeneity and tumor microenvironment in recurrent and drug-resistant GBMs at a single-cell resolution and further explore the mechanism of drug resistance of GBMs. We analyzed six tumor tissue samples from three patients with primary GBM and three patients with recurrent GBM in which recurrence and drug resistance developed after treatment with the standard Stupp protocol using single-cell RNA sequencing. Using unbiased clustering, nine major cell clusters were identified. Upregulation of the expression of stemness-related and cell-cycle-related genes was observed in recurrent GBM cells. Compared with the initial GBM tissues, recurrent GBM tissues showed a decreased proportion of microglia, consistent with previous reports. Finally, vascular endothelial growth factor A expression and the blood-brain barrier permeability were high, and the O6 -methylguanine DNA methyltransferase-related signaling pathway was activated in recurrent GBM. Our results delineate the single-cell map of recurrent glioblastoma, tumor heterogeneity, tumor microenvironment, and drug-resistance mechanisms, providing new insights into treatment strategies for recurrent glioblastomas.

Anti-SARS-CoV-2 IgM Secondary Response Was Suppressed by Preexisting Immunity in Vaccinees: A Prospective, Longitudinal Cohort Study over 456 Days.

To obtain more insight into IgM in anti-SARS-CoV-2 immunity a prospective cohort study was carried out in 32 volunteers to longitudinally profile the kinetics of the anti-SARS-CoV-2 IgM response induced by administration of a three-dose inactivated SARS-CoV-2 vaccine regimen at 19 serial time points over 456 days. The first and second doses were considered primary immunization, while the third dose was considered secondary immunization. IgM antibodies showed a low secondary response that was different from the other three antibodies (neutralizing, total, and IgG antibodies). There were 31.25% (10/32) (95% CI, 14.30-48.20%) of participants who never achieved a positive IgM antibody conversion over 456 days after vaccination. The seropositivity rate of IgM antibodies was 68.75% (22/32) (95% CI, 51.80-85.70%) after primary immunization. Unexpectedly, after secondary immunization the seropositivity response rate was only 9.38% (3/32) (95% CI, 1.30-20.10%), which was much lower than that after primary immunization (p = 0.000). Spearman's correlation analysis indicated a poor correlation of IgM antibodies with the other three antibodies. IgM response in vaccinees was completely different from the response patterns of neutralizing, total, and IgG antibodies following both the primary immunization and the secondary immunization and was suppressed by pre-existing immunity induced by primary immunization.

Treponema pallidum membrane protein Tp47 promotes angiogenesis through ROS-induced autophagy.

BACKGROUND: Pathological angiogenesis is an important manifestation of syphilis, but the underlying mechanism of Treponema pallidum subspecies pallidum (T. pallidum)-induced angiogenesis is poorly understood. OBJECTIVES: The objective of this study is to investigate the role and related mechanism of the T. pallidum membrane protein Tp47 in angiogenesis. METHODS: The proangiogenic activity of recombinant T. pallidum membrane protein Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed by tube formation assay, three-dimensional angiogenesis analysis and experiments with a zebrafish embryo model. The effects of mitochondrial ROS and NADPH oxidase on intracellular ROS induced by Tp47 were further investigated. Furthermore, the levels of autophagy-related proteins and autophagic flux were measured. Finally, the role of ROS-induced autophagy in angiogenesis was studied. RESULTS: Tp47 promoted tubule formation and the formation of angiogenic sprouts in vitro. In addition, a significant increase in the number of subintestinal vessel branch points in zebrafish injected with Tp47 was observed using a zebrafish embryo model. Tp47 also significantly increased intracellular ROS levels in a dose-dependent manner. Tp47-induced tube formation and angiogenic sprout formation were effectively prevented by the ROS inhibitor NAC. In addition, Tp47 enhanced the production of mitochondrial ROS and expression of the NADPH oxidase-related proteins Nox2 and Nox4. The production of mitochondrial ROS and intracellular ROS was reduced by the NADPH oxidase inhibitors DPI and apocynin. Furthermore, Tp47 significantly increased expression of the autophagy-related proteins P62 and Beclin 1 and the LC3-II/LC3-I ratio and promoted an increase in autophagic flux, which could be effectively rescued by coincubation with the ROS inhibitor NAC. Further intervention with the autophagy inhibitor BafA1 significantly inhibited tube formation and angiogenic sprout formation. CONCLUSIONS: Tp47-induced NADPH oxidase enhanced intracellular ROS production via mitochondrial ROS and promoted angiogenesis through autophagy mediated by ROS. These findings may contribute to our understanding of pathological angiogenesis in syphilis.

Development and external validation of a simple nomogram for predicting apnea in children hospitalized with bronchiolitis.

Background: Apnea is one of the most life-threatening complications of bronchiolitis in children. This study aimed to determine early predictors of apnea in children hospitalized with bronchiolitis and develop a simple nomogram to identify patients at risk of apnea. Methods: This retrospective, observational study included children hospitalized with bronchiolitis in two hospitals in China. Demographic and clinical characteristics, laboratory results, pathogens, and pulmonary iconography results were recorded. A training cohort of 759 patients (one hospital) was used to identify early predictors of apnea during hospitalization. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection. The nomogram was developed visually based on the variables selected by multivariable logistic regression analysis. Discrimination (concordance index, C-index), calibration, and decision curve analysis (DCA) were used to assess the model performance and clinical effectiveness. Results: A total of 1,372 children hospitalized with bronchiolitis were retrospectively evaluated, 133 (9.69%) of whom had apnea. Apnea was observed in 80 of the 759 patients with bronchiolitis in the training cohort and 53 of the 613 patients in the external validation cohort. Underlying diseases, feeding difficulties, tachypnea, retractions and pulmonary atelectasis in the training cohort were independent risk factors for apnea and were assembled into the nomogram. The nomogram exhibited good discrimination with a C-index of 0.883 (95% CI: 0.839-0.927) and good calibration. The DCA showed that the nomogram was clinically useful in estimating the net benefit to patients. Conclusion: We developed a nomogram that is convenient to use and able to identify the individualized prediction of apnea risk in patients with bronchiolitis. These patients might benefit from early triage and more intensive monitoring.

Prognostic value of the modified systemic inflammation score in non-small-cell lung cancer with brain metastasis.

BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. METHODS: A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan-Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. RESULTS: The optimal cut-off value of the neutrophil-lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer's (AJCC) 7th T + N staging system in the training cohort (Harrell's concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC's 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC's 7th T + N staging system in NSCLC patients with BM. CONCLUSION: The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.

Evaluation of the efficacy of four anti-SARS-CoV-2 antibodies after vaccination using kits from two manufacturers: A prospective, longitudinal, cohort study at 11 serial time points within 160 days.

PURPOSE: The accuracy of level of anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a great concern. We aimed to compare the efficacy of anti-SARS-CoV-2 antibody detection kits from two manufacturers in evaluating the efficacy of SARS-CoV-2 vaccines. METHODS: The immune responses and consistency of four anti-SARS-CoV-2 antibodies were evaluated using two manufacturers' antibody kits (A and B) in 61 subjects within 160 days after vaccination with the CoronaVac vaccine. RESULTS: The total seropositivity rates of neutralizing antibodies and IgM antibodies detected by kit A were higher than those detected by kit B (P = 0.003 and P < 0.001, respectively). Conversely, the total seropositivity rates of total antibodies and IgG antibodies were higher in kit B than kit A (P < 0.001 and P < 0.001, respectively). The consistency rates showed less than 90% agreement between the kits for the detection of the four antibodies, and the κ score showed moderate or substantial consistency. The half-lives of neutralizing antibodies, total antibodies, and IgG antibodies within 160 days after vaccination, detected by kit A were 63.88 days, 80.50 days, and 63.70 days, respectively and by kit B were 97.06 days, 65.41 days, and 77.99 days, respectively. CONCLUSION: The efficacy of antibody detection differed between the two commercial anti-SARS-CoV-2 antibody kits, although there was moderate consistency, which may affect the clinical application and formulation of the vaccine strategy.

Does financial inclusion promote investment and affect residents' happiness?-Evidence from China.

With the rapid development of inclusive finance, the popularity of financial services is increasing, and the level of financial literacy of residents has gained. Using data from the years 2013, 2015, and 2017 China General Social Surveys (CGSS) and the China Digital Inclusive Finance Development Index to analyze residents' investment behavior in China, this study finds that inclusive finance significantly increased residents' investment participation and decrease their sense of happiness at the same time. This study demonstrates the effectiveness of China's financial inclusion policy and provides ideas for its further improvement.

Membrane location of cardiolipin antigen in Treponema pallidum: further study on the origin of nontreponemal antibodies.

Aim: The present study examined the membrane location of cardiolipin antigen in treponemes. Materials & methods: The authors used different methods to disrupt the outer membrane of treponemes, detected the location of the cardiolipin antigen and analyzed the immune response in rabbits immunized with various antigens. Results: All organisms were labeled with nontreponemal antibodies on immunoelectron and fluorescence microscopy, except the citrate buffer-treated group, which is a method leading to relatively complete removal. Except for citrate buffer-treated spirochetes, all treponemes produced low-titer, nontreponemal antibodies in immunized rabbits. Conclusion: These findings indicated that the cardiolipin antigen was localized in the outer membrane of spirochetes. This study provided further evidence of the origin of nontreponemal antibodies during Treponema pallidum infection.

Effect of Bairui Granule on Inflammatory Mediators in Induced Sputum, Leukotriene C4, and EOS in Peripheral Blood of Children with Cough Variant Asthma.

Objective: To study the effect of Hanchuan Zupa granule combined with conventional western medicine in the treatment of children with bronchial asthma. Methods: 98 cases in Fengrun District People's Hospital of Tangshan City from June 2018 to February 2021 were selected. The control group was given oxygen therapy, antibiotics, and aerosol inhalation of quick acting ß 2 receptor agonist, glucocorticoid, and other conventional western medicine treatment, while the observation group was treated with Bairui granule on the basis of the control group. The course of treatment of the two groups was 1 week. Results: After treatment, the levels of sputum IL-4, IL-17, neu, and ECP in the two groups decreased, and the observation group was lower than the control group (P < 0.05). The levels of EOS, CXCR4, LTB4, and SDF-1 in peripheral blood of the two groups were lower than those in the control group (P < 0.05). The daytime cough, night cough, and TCM syndrome scores of the two groups were decreased, and the observation group was lower than the control group (P < 0.05). Conclusion: Bairui granule combined with conventional western medicine in the treatment of children with bronchial asthma, the curative effect is worthy of affirmation, can effectively improve cough symptoms, reduce EOS, CXCR, LTB4, SDF-1 levels, inhibit airway inflammation, and has good clinical application value.

A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days.

Background: Due to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection. Objectives: To evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens. Methods: A prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days. Results: The neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)). Conclusions: Compared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.

Which Is the Optimum Antigen Concentration for the Venereal Disease Research Laboratory Test of Cerebrospinal Fluid for Neurosyphilis Diagnosis: 10 or 17 µL?

The manufacturer's instructions for the venereal disease research laboratory (VDRL) antigen test for diagnosing neurosyphilis describe testing of serum samples and do not include procedures for cerebrospinal fluid (CSF) testing. This study compared the CSF-VDRL test with 10 µL of antigen (CSF-VDRL-10) according to the American Public Health Association to the CSF-VDRL test with 17 µL of antigen (CSF-VDRL-17) according to the VDRL serum procedure. A total of 121 neurosyphilis patients and 86 syphilis/non-neurosyphilis patients were included. The sensitivities of the CSF-VDRL-10 and CSF-VDRL-17 tests were comparable for neurosyphilis diagnosis. The positive rate of the CSF-VDRL-17 test was higher than that of the CSF-VDRL-10 test. In all, 78.3% of the quantitative CSF-VDRL-17 results were consistent with those of the CSF-VDRL-10 test, 18.4% exhibited one-titer higher results than those of the CSF-VDRL-10 test, and 3.4% had positive CSF-VDRL-17 results but negative CSF-VDRL-10 results. The CSF-VDRL test with 17 µL of antigen was more sensitive, and it is worth performing longitudinal studies to understand its practical implications.

Anti-Receptor-Binding Domain Immunoglobulin G Antibody as a Predictor of Seropositivity for Anti-SARS-CoV-2 Neutralizing Antibody.

CONTEXT.­: Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors. OBJECTIVE.­: To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs. DESIGN.­: The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination. RESULTS.­: The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P < .001). The area under the receiver operating characteristic curve for total antibody levels for the prediction of seropositivity for neutralizing antibodies was 0.881 (P < .001), and that for anti-RBD IgG antibody levels was 0.937 (P < .001). CONCLUSIONS.­: Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination.