Discovery of new antigens for serodiagnosis of visceral leishmaniasis in humans and dogs adds valuable tools to our arsenal.

Surveillance and sustained control of visceral leishmaniasis (VL) require reliable serodiagnostic tools. rK39, the gold standard antigen for VL diagnosis, is limited by its documented poor sensitivity in certain endemic regions, such as East Africa, and by the longevity of its antibodies, making it difficult to distinguish active from cured infections. In a recent publication in mBio, Roberts et al. (A. J. Roberts, H.B. Ong, S. Clare, C. Brandt, et al., mBio 15:e00859-24, 2024, https://doi.org/10.1128/mbio.00859-24) identified new immunogenic Leishmania candidates in dogs and humans. In dogs, combined antigens LdBPK_290790.1 + LdBPK_362700.1 (D4 +D46) distinguished symptomatic from asymptomatic infections. For humans, LdBPK_323600.1 (D36) antigen produced short-lived antibodies and performed well in patient cohorts from Bangladesh and Ethiopia, but not Kenya. This study adds promising new candidates to our serodiagnostic toolbox but highlights the need for more antigen discovery studies that may have to be focused on regional performance.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice.

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.

Relationship of various COVID-19 antibody titer with individual characteristics and prediction of future epidemic trend in Xiamen City, China.

Background: Reinfection of coronavirus disease 2019 (COVID-19) has raised concerns about how reliable immunity from infection and vaccination is. With mass testing for the virus halted, understanding the current prevalence of COVID-19 is crucial. This study investigated 1,191 public health workers at the Xiamen Center for Disease Control, focusing on changes in antibody titers and their relationship with individual characteristics. Methods: The study began by describing the epidemiological characteristics of the study participants. Multilinear regression (MLR) models were employed to explore the associations between individual attributes and antibody titers. Additionally, group-based trajectory models (GBTMs) were utilized to identify trajectories in antibody titer changes. To predict and simulate future epidemic trends and examine the correlation of antibody decay with epidemics, a high-dimensional transmission dynamics model was constructed. Results: Analysis of epidemiological characteristics revealed significant differences in vaccination status between infected and non-infected groups (χ2=376.706, P<0.05). However, the distribution of antibody titers among the infected and vaccinated populations was not significantly different. The MLR model identified age as a common factor affecting titers of immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibody (NAb), while other factors showed varying impacts. History of pulmonary disease and hospitalization influenced IgG titer, and factors such as gender, smoking, family history of pulmonary diseases, and hospitalization impacted NAb titers. Age was the sole determinant of IgM titers in this study. GBTM analysis indicated a "gradual decline type" trajectory for IgG (95.65%), while IgM and NAb titers remained stable over the study period. The high-dimensional transmission dynamics model predicted and simulated peak epidemic periods in Xiamen City, which correlated with IgG decay. Age-group-specific simulations revealed a higher incidence and infection rate among individuals aged 30-39 years during both the second and third peaks, followed by those aged 40-49, 50-59, 18-29, and 70-79 years. Conclusions: Our study shows that antibody titer could be influenced by age, previous pulmonary diseases as well as smoking. Furthermore, the decline in IgG titers is consistent with epidemic trends. These findings emphasize the need for further exploration of these factors and the development of optimized self-protection countermeasures against reinfection.

Neutralization of Rubella Vaccine Virus and Immunodeficiency-Related Vaccine-Derived Rubella Viruses by Intravenous Immunoglobulins.

The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immune deficiencies (PID) has raised concerns about the ability of immunoglobulin (IG) preparations to neutralize VDRVs. We investigated the capacity of IG to neutralize rubella vaccine virus and four VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by IG preparations; however, the VDRV isolates from patients after intra-host evolution, 2-6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while IG replacement therapy can be expected to provide protection from rubella virus infection.

The occurrence of granulomas associated with vaccine derived rubella viruses (VDRV) in people with primary immune deficiencies (PID) challenges immunoglobulin (IG) preparations regarding their rubella neutralizing ability. This study confirmed potent rubella virus neutralization capacity of IG preparations and thus suggests protection of IG-treated PID patients against rubella. The study also highlights the importance of early diagnosis and timely given IG to prevent possible systemic spread of VDRV persisting locally in granulomas.

Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. METHODS: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. RESULTS: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. CONCLUSIONS: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

[Feasibility Analysis of Establishing Combat Readiness Blood Bank Based on Low Titer Group O Whole Blood and Group A Plasma].

OBJECTIVE: To explore the feasibility of establishing combat readiness blood bank with low titer group O whole blood and group A plasma. METHODS: The Galileo automatic blood analyzer was used to detect the titers of IgM anti-A and anti-B antibodies in the samples of group O blood donors and IgM anti-B titer in the samples of group A blood donors. Group O blood donors with antibody titers below 128 were selected and included in the mobile blood bank for combat readiness, group A plasma with anti-B titer lower than 128 and group O whole blood with antibody titers below 128 were included in the combat readiness entity blood bank. RESULTS: A total of 1 452 group O blood donors were selected, and the anti-A/B antibody titers were detected. Both antibody titers were distributed below 512, and both peak values of sample distribution were at titer 4. The proportion of samples with titers>128 for both antibodies was relatively low. There was a significant positive correlation between the titers of the two antibodies (r =0.383), and the proportion of samples with IgM anti-A titer higher than IgM anti-B titer was relatively high. 1 335(91.94%) group O blood donors with IgM anti-A and anti-B antibody titers <128 could be included in the mobile blood bank. The anti-B titer of group A blood was detected in 512 cases and the results showed that as the antibody titer increased, the proportion of blood donors gradually decreased. 99.8% of group A blood donors had anti-B antibody titer less than 128, and only one case did not meet the inclusion criteria. CONCLUSION: The proportion of group O blood donors whose whole blood meet the low antibody titer standard is high, and almost all plasma of group A blood donors meet the low titer standard, which improves the blood supply rate in emergencies.

Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

A study of the immunomodulatory effects of coconut oil extract in broilers experimentally infected with velogenic Newcastle disease virus.

Objective: This study aims to evaluate the immunomodulatory effects of coconut oil extract (COE) in broilers experimentally infected with velogenic Newcastle disease virus (vNDV). Methods: A total of 150 broiler birds (day-old) were equally divided into five study groups i.e., negative control, positive control, COE-1, COE-2, and COE-3. On day 10, broilers of groups COE-1, COE-2, and COE-3 were supplemented with 1, 2, and 3 ml of COE respectively per liter of drinking water for 15 days. On day 13, 0.1ml/bird (10-5.25 ELD50) of vNDV was inoculated in broilers of positive control, COE-1, COE-2, and COE-3 groups intramuscularly. During this study, growth performance, morbidity, and mortality rates of each study group were recorded. The antibody titer against NDV was determined on days 7, 14, 21, 28, and 35. The levels of IgY and IgM were also determined on the 7th, 14th, and 21st days post-SRBC inoculation. On day 33, avian tuberculin was injected between the 1st and 2nd toes of the left side (intradermally) to measure lymphoproliferative responses. On day 35, the phagocytic activity in the blood was assessed through a carbon clearance assay by injecting carbon black ink into the right-wing vein. The visceral organs having gross lesions were also collected for histopathology. Results: The COE significantly improved the growth performance, and lowered the morbidity and mortality rates of broilers. There was a significant rise in antibody titers against NDV and levels of IgY and IgM antibodies against SRBC in COE-supplemented broilers. The lymphoproliferative response and phagocytic activity were also enhanced. Among COE-supplemented groups, the broilers of the COE-3 group showed a significant increase in growth performance and boosted immune defense. Conclusions: Coconut oil extract has the potential to boost the growth performance and immune status of broilers. It can be used effectively as a feed additive and alternative to antibiotics to prevent the spread of infectious poultry pathogens.

Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

Immune response enhancement by dietary supplementation with Caesalpinia sappan extract in weaned pigs challenged with porcine reproductive and respiratory syndrome virus.

BACKGROUND: At present, porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most severe epidemics impacting pig farming globally. Despite the fact that a number of studies have been conducted on potential solutions to this problem, none have proven effective. The focus of problem solving is the use of natural ingredients such as plant extracts. Popular throughout Asia, Caesalpinia sappan (CS) is a therapeutic plant that inhibits PRRSV in vitro. Therefore, this study was performed to determine the efficacy of CS extract dietary supplementation on the productive performance, antibody levels, immunological indicators, and lung pathology of PRRSV-challenged weaned pigs. A total of 32 weaned piglets (28 days old) were randomized into 4 groups and kept separately for 14 days. The treatments were organized in a 2 × 2 factorial design involving two factors: PRRSV challenge and supplementation with 1 mg/kg CS extract. The pigs in the PRRSV-challenged groups were intranasally inoculated with 2 mL of PRRSV (VR2332) containing 104 TCID50/mL, while those in the groups not challenged with PRRSV were inoculated with 2 mL of normal saline. RESULTS: In the PRRSV-challenged group (CS + PRRSV), supplementation with CS extract led to an increase in white blood cells (WBCs) on Day 7 post infection (p < 0.05) and particularly in lymphocytes on Days 7 and 14. The antibody titer was significantly greater in the CS + PRRSV group than in the PRRSV-challenged group not administered CS (PRRSV group) on Day 14 postinfection (S/P = 1.19 vs. 0.78). In addition, CS extract administration decreased the prevalence of pulmonary lesions, which were more prevalent in the PRRSV-challenged pigs that did not receive the CS extract. CONCLUSION: The findings of this study suggest that supplementation with CS extract is beneficial for increasing WBC counts, especially lymphocytes, increasing the levels of antibodies and reducing the prevalence of lung lesions in PRRSV-infected pigs.

Repeated AAV9 Titer Determination in a Presymptomatic SMA Patient with Three SMN2 Gene Copies - A Case Report.

Adeno-associated viruses (AAV) are well-suited to serve as gene transfer vectors. Onasemnogene abeparvovec uses AAV9 as virus vector. Previous exposure to wild-type AAVs or placental transfer of maternal AAV antibodies, however, can trigger an immune response to the vector virus which may limit the therapeutic effectiveness of gene transfer and impact safety. We present the case of a female patient with spinal muscular atrophy (SMA) and three survival motor neuron 2 (SMN2) gene copies. The infant had elevated titers of AAV9 antibodies at diagnosis at 9 days of age. Being presymptomatic at diagnosis, it was decided to retest the patient's AAV9 antibody titer at two-weekly intervals. Six weeks after initial diagnosis, a titer of 1:12.5 allowed treatment with onasemnogene abeparvovec. The presented case demonstrates that, provided the number of SMN2 gene copies and the absence of symptoms allow, onasemnogene abeparvovec therapy is feasible in patients with initially exclusionary AAV9 antibody titers of >1:50.

Effect of Organic Selenium Supplementation on the Antioxidant Status, Immune Response, and the Relative Expression of IL-2 and IFN-γ Genes in Ewes During the Hot Season.

This study was conducted to evaluate the effects of different doses of selenium (Se) from Sel-Plex© (selenium-enriched Saccharomyces cerevisiae yeast) supplement on the antioxidant status, the antibody titers against the foot-and-mouth disease virus, and the expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes in ewes during the hot season. Six ewes were kept at 25 °C and received basal diet (the negative control group), and 24 ewes were kept at 38 °C for 5 h per day and received no supplement (the positive control), 0.15, 0.30, and 0.45 mg Se/kg. Ewes in the positive control had higher (P<0.001) liver enzyme activity, malondialdehyde (MDA), and cortisol levels, and lower antibody titer than the negative control. The liver enzymes' lowest (P<0.001) activities were observed in ewes receiving 0.30 and 0.45 mg Se/kg. Ewes receiving 0.30 and 0.45 mg Se/kg had lower MDA levels than other treatments. Ewes receiving 0.30 and 0.45 mg Se/kg had higher (P<0.001) total antioxidant capacity levels than those receiving 0.15 mg Se/kg and the positive control. Se-supplemented groups had lower (P<0.001) relative expression of IL-2 and higher (P<0.04) expression of IFN-γ than the positive control. The antibody titer was the same in the positive control and the group receiving 0.15 mg Se/kg. Ewes fed a diet with 0.30 and 0.45 mg Se/kg had higher (P<0.011) antibody titer than the positive control. The Se supplementation can reverse the decrease of antioxidant capacity and immune function caused by heat stress, and 0.3 mg Se/kg from Sel-Plex©is the best dose.

ANCA detection with solid phase chemiluminescence assay: diagnostic and severity association in vasculitis.

ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.

Effect of citrus peeling (Citrus sinensis) on production performance, humoral immunity, nutrients, and energy utilization of broiler quails.

Citrus citrus peeling has a wide range of vitamins and trace minerals that have antioxidant and antimicrobial properties. It is hypothesized that the addition of citrus peeling to broiler quail diets can improve their production performance, humoral immunity, nutrients, and energy utilization. A trial was performed to study the impact of a methanolic extract of citrus peeling (Citrus sinensis) on production performance, humoral immunity, nutrients, and energy utilization of broiler quails. A healthy day-old 300 quails were randomly assigned with 5 replicates each replicate had 15 birds and used CRD for the trial. Different dietary supplementations were presented to different groups. The control group was not supplemented with any supplementation in their feed. While, the 3 other groups were supplemented by 0.5 mL/kg, 1 mL/kg, and 1.5 mL/kg of methanolic extract of dried Citrus sinensis peel (DCSP) in the basal diet (DCSP0.5, DCSP1, and DCSP1.5 groups, respectively). All the birds were allowed ad libitum feeding and water. The feed intake and FCR were significantly higher in the control group, followed by DCSP0.5, and then DCSP1. The significantly lowest feed intake and FCR were observed in the DCSP1.5 group. The weight gain and dressing % were significantly improved with the increasing level of methanolic extract of Citrus sinensis. The significantly highest weights of thymus, spleen, and bursa were recorded in the DCSP1.5 group, followed by the DCSP1. The antibody titers against infectious bursal disease, New Castle disease, and infectious bronchitis disease were significantly higher in the DCSP1.5, DCSP1, and DCSP0.5 groups than in the control group. It was concluded from the study that supplementation of quails with methanolic extract of citrus at a dose rate of 0.5 to 1.5 mL/kg of feed can improve feed intake, weight gain, FCR, dressing percentage, relative weight of lymphoid organs, and digestibility coefficient. Supplementation of Citrus sinensis has also concluded positive impacts on antibody titers against various viral diseases. The best improvement in the evaluated parameters was observed at a dose of extract of citrus was 1.5 mL/kg of feed.

A Dynamic Model for Estimating the Retention Duration of Neutralizing Antibody Titers After Vaccination in a COVID-19 Convalescent Population.

We measured neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cohort of 235 convalescent patients (representing 384 analytic samples). They were followed for up to 588 days after the first report of onset in Taiwan. A proposed Bayesian approach was used to estimate nAb dynamics in patients postvaccination. This model revealed that the titer reached its peak (1819.70 IU/mL) by 161 days postvaccination and decreased to 154.18 IU/mL by day 360. Thus, the nAb titers declined in 6 months after vaccination. Protection, against variant B.1.1.529 (ie, Omicron) may only occur during the peak period.

Immunomodulatory effect of Atractylodis macrocephala Koidz. polysaccharides in vitro.

Vaccination is still the main method of preventing most infectious diseases, but there are inefficiencies and inaccuracies in immunization. Studies have reported that Atractylodis macrocephalae Koidz. polysaccharides (RAMP) have immunomodulatory effects, but the mechanisms involved in whether they can modulate the immune response in chickens are not yet clear. The aim of this study was to investigate the effect of RAMP on lymphocytes functions by analyzing cell proliferation, cell cycle, mRNA expression of cytokines and CD4 +/CD8 + ratio. To identify potential molecules involved in immune regulation, we performed a comprehensive transcriptome profiling of chicken lymphocytes. In addition, the adjuvant effect of RAMP was evaluated by detecting indicators of hemagglutination inhibition. When lymphocytes were cultured with RAMP in vitro, the proliferation rate of lymphocytes was increased (P < 0.01), more cells in S phase and G2/M phase (P < 0.01) and the mRNA expression of IFN-γ was upregulated (P < 0.05), while the mRNA expression of TGF-ß (P < 0.01) and IL-4 (P < 0.05) was downregulated and the CD4 +/CD8 + ratio was increased (P < 0.05). Transcriptomic results showed that RAMP increased the expression of HIST1H46 (P < 0.05) and CENPP (P < 0.05). Validation of qPCR showed that RAMP may play an important role in regulating cellular immunity by downregulating the Notch pathway. The results also showed that RAMP could increase the serum Newcastle disease virus antibody levels in chickens. These data suggest that RAMP could enhance immune function of lymphocytes and was a candidate vaccine adjuvant in chickens.

Effect of adenosine and cordycepin on recombinant antibody production yields in two different Chinease hamster ovary cell lines.

In this study, we investigated the effect of adenosine and its derivative cordycepin on the production yield of a recombinant human monoclonal antibody (adalimumab) in two commonly used Chinese Hamster ovary (CHO) cell lines that have different gene amplification systems, namely CHO-DHFR- and GS-CHO knockout (GS-KO CHO) cells and that were grown in batch culture, with and without glucose feeding. The results showed that adenosine suppressed the cell growth rate and increased the fraction of cells in S phase of the cell cycle for both CHO cell lines. Different concentrations and exposure times of adenosine feeding were tested. The optimal yield of adalimumab production was achieved with the addition of 1 mM adenosine on day 2 after start of the batch culture. Adenosine could significantly improve antibody titers and productivity in both CHO cell lines in cultures without glucose feeding. However, upon glucose feeding, adenosine did not improve antibody titers in CHO-DHFR- cells but extended culture duration and significantly increased antibody titers in GS-KO CHO cells. Therefore, adenosine supplementation might be useful for antibody production in GS-KO CHO cells in medium- to large-scale batches. In case of cordycepin, a derivative of adenosine, CHO-DHFR- cells required higher concentration of cordycepin than GS-KO CHO cells around 10 times to display the changes in cell growth and cell cycle. Moreover, cordycepin could significantly increase antibody titers only in CHO-DHFR- cell cultures without glucose feeding.

Outcomes of ABO-Incompatible Living Donor Kidney Transplantation Compared to Waiting or Deceased Donor Kidney Transplantation.

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.

Difference in the Dynamics of Antibody Titers between COVID-19 Vaccination and SARS-CoV-2 Infection in Healthcare Workers - A Case Study Based on Long-Term and Densely Repeated Measurements of Antibody Titers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1-2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4-8 weeks after infection, and the antibody titer remained elevated up to 16-40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.