Non-specific Immune Activation Research Articles

No neutralizing effect of pre-existing tick-borne encephalitis virus antibodies against severe acute respiratory syndrome coronavirus-2: a prospective healthcare worker study

Certain immunizations including vaccination against tick-borne encephalitis virus (TBEV) have been suggested to confer cross-protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with ≥ 1 previous TBEV vaccination (n = 2018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7–1.0, P = 0.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p = 0.001) and total IgG (P < 0.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that the observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 infection is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations.

Effects of dietary Zn on growth, antioxidant capacity, immunity and tolerance to lipopolysaccharide challenge in juvenile Chinese mitten crab Eriocheir sinensis

Zinc (Zn) is an essential trace mineral element in organisms and is involved in physiological processes. This study investigates the effects of dietary Zn on the growth, antioxidant capacity, non-specific immunity and disease resistance of juvenile Chinese mitten crab. Zn was supplemented, respectively, at 0 (control), 25, 50, 100, 200 and 400 mg/kg to the basal diet to form six diets as Zn0, Zn25, Zn50, Zn100, Zn200 and Zn400. Each diet was separately used to feed the crabs (0.40 ± 0.01 g) for 56 days. Diet without Zn supplementation led to a higher feed intake rate, a lower Zn content in the hepatopancreas and a lower non-specific immune enzyme activity than other groups with Zn supplement. The results also showed that compared with the control group: (1) The final weight, weight gain rate, specific growth rate, Zn in the hepatopancreas, body crude protein and the activities of serum alkaline phosphatase (AKP), acid phosphatase (ACP) and copper-zinc superoxidase (CuZnSOD) were significantly increased in the Zn100 group. (2) Moreover, Zn accumulation in the hepatopancreas and body ash were significantly increased in the Zn200 group, and the antioxidant enzyme activities such as CuZnSOD and glutathione peroxidase (GSH-Px) in the hepatopancreas were significantly increased. (3) In addition, the addition of Zn can activate the TLRs/NF-κB pathway after the lipopolysaccharide (LPS) injection, resulting in upregulation of the relative mRNA expression of antimicrobial peptide (ALFs). This study demonstrates that dietary Zn supplements can significantly improve growth performance, antioxidant capacity, non-specific immunity and disease resistance of juvenile crabs. The regression analysis showed that the optimal dietary Zn level was 94.87 mg/kg for weight gain and 96.96 mg/kg for specific growth.

An Analysis of Virus Amplification and Antitumor Responses in T-Cell Lymphoma Patients Treated with Voyager-V1 ( VSV-IFNβ-NIS)

An Analysis of Virus Amplification and Antitumor Responses in T-Cell Lymphoma Patients Treated with Voyager-V1 ( VSV-IFNβ-NIS)

Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy.

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

Evaluation of the effect of enzymatic hydrolyzate of the bursa of broiler chickens on cytotoxic activity and nonspecific immunity

The use of biologically active substances of tissue origin for the creation of biologically active additives and immunomodulatory drugs is an important area of scientific research in the field of nutrition and pharmacology. The aim of the work is to evaluate the effect of enzymatic hydrolysate from the fabricium bag of broiler chickens on the cytotoxicity and nonspecific immunity of mice against the background of experimental salmonella infection using biotechnological methods. For the experiment, three equal experimental groups of white mongrel mice were formed. All laboratory animals were fed daily for seven days with enzymatic hydrolysate at a dose of 750 mg/kg (therapeutic dose), 150 mg/kg (0.2 therapeutic dose) and 3,750 mg/kg (five therapeutic doses). At the same time, the control group of animals received intragastric water in the same volume. 24 hours after the last intake of the enzymatic hydrolysate, the animals were intraperitoneally infected with a culture of Salmonella enteritidis 92. The study reveals the absence of cytotoxic properties and impaired cell viability in cultures L929, J774.1A, HeLa S3, K562, and HST116 against the background of exposure to various concentrations of enzymatic hydrolysate from 0.02 to 10 mg/ml. It should be noted that there is a pronounced cytotoxic effect on MCF-7 tumor cells of the concentration of enzymatic hydrolysate in culture of 5 and 10 mg/ml, which suggests the possibility of using enzymatic hydrolysate for the prevention of tumor diseases. As a result of the experiment, it has been proved that the administration of enzymatic hydrolysate to mice increased the LD50 index and the survival rate of mice infected with the culture of the causative agent of salmonellosis by 1.5 times. Based on the conducted studies, it has been shown that the enzymatic hydrolysate of the lymphoid tissue of broiler chickens does not violate the viability of mammalian cells and does not exhibit cytotoxic properties on the metabolism of healthy mammalian cells, which indicates its safety. In an experiment on mice, the effect of enzymatic hydrolysate of the fabricium bag of broiler chickens on the activation of nonspecific immunity against salmonella infection has been revealed.

Cardiotoxicity of Cancer Treatments: Focus on Anthracycline Cardiomyopathy.

Significant progress has been made in developing new treatments and refining the use of preexisting ones against cancer. Their successful use and the longer survival of cancer patients have been associated with reports of new cardiotoxicities and the better characterization of the previously known cardiac complications. Immunotherapies with monoclonal antibodies against specific cancer-promoting genes, chimeric antigen receptor T cells, and immune checkpoint inhibitors have been developed to fight cancer cells, but they can also show off-target effects on the heart. Some of these cardiotoxicities are thought to be due to nonspecific immune activation and inflammatory damage. Unlike immunotherapy-associated cardiotoxicities which are relatively new entities, there is extensive literature on anthracycline-induced cardiomyopathy. Here, we provide a brief overview of the cardiotoxicities of immunotherapies for the purpose of distinguishing them from anthracycline cardiomyopathy. This is especially relevant as the expansion of oncological treatments presents greater diagnostic challenges in determining the cause of cardiac dysfunction in cancer survivors with a history of multiple cancer treatments including anthracyclines and immunotherapies administered concurrently or serially over time. We then provide a focused review of the mechanisms proposed to underlie the development of anthracycline cardiomyopathy based on experimental data mostly in mouse models. Insights into its pathogenesis may stimulate the development of new strategies to identify patients who are susceptible to anthracycline cardiomyopathy while permitting low cardiac risk patients to receive optimal treatment for their cancer.

Effects of dietary manganese supplementation on growth performance, antioxidant capacity, immune function and intestinal microbiota in Pacific white shrimp Litopenaeus vannamei

Water manganese (Mn) is apparently insufficient to meet aquatic animals’ metabolic requirement, and their food is considered as the major Mn source. Currently, researches reporting the effects of dietary Mn inclusion on physiological and metabolic function in Litopenaeus vannamei (L. vannamei) are very scarce. Therefore, 8-week feeding trail was conducted to determine dietary Mn requirement for L. vannamei and further evaluate the effects of dietary Mn supplementation on tissue Mn concentration, antioxidant enzyme activity, nonspecific immune enzymes activity and intestinal microbiota composition. Our results demonstrated that the optimum dietary Mn requirement for L. vannamei was determined to be 44.83 mg/kg based on the per cent weight gain; supplementing 39.57 mg/kg, 54.57 mg/kg and 72.67 mg/kg Mn significantly increased (p < .05) the activity of serum lysozyme (LZM), nitric oxide synthase and alkaline phosphatase, the activity of antioxidative capacity and glutathione in serum and hepatopancreas of L. vannamei. Supplementing 111.97 mg/kg Mn significantly increased (p < .05) hepatopancreas Mn concentration and serum LZM activity. Intestinal microbiota analysis showed that supplementing 39.57 mg/kg and 111.97 mg/kg Mn significantly influenced (p < .05) intestinal microbiota composition and function. These findings might help provide a scientific basis for the commercial application of Mn in L. vannamei.

Effects of replacing fishmeal with soybean protein concentrate (SPC) on growth, blood biochemical indexes, non-specific immune enzyme activity, and nutrient apparent digestibility for juvenile Litopenaeus vannamei

Effects of replacing fishmeal with soybean protein concentrate (SPC) on growth, blood biochemical indexes, non-specific immune enzyme activity, and nutrient apparent digestibility for juvenile Litopenaeus vannamei

Treatment recommendations for nail unit toxicities secondary to targeted cancer therapy based on collective experience and evidence-based literature review

To the Editor: Dermatologic toxicities are often the earliest-presenting and highest-incidence adverse events (AEs) due to targeted anticancer therapies and immunotherapies.1 Nail unit toxicities due to immunotherapy are caused by nonspecific immune activation. Targeted therapies, particularly mitogen-activated protein kinase pathway inhibitors, lead to epidermal thinning of the nailfolds and periungual tissue, increasing susceptibility to trauma and penetration by nail plate fragments. Paronychia may develop and evolve into onychocryptosis.

Enhanced immunity and hemocytes proliferation by three immunostimulants in tri-spine horseshoe crab Tachypleus tridentatus

Tachypleus amebocyte lysate (TAL) is crucial in medical testing, but its industry in China has been restricted due to the decline of horseshoe crab population in recent years. Exploring methods of enhancing immunity and rapid hemocytes proliferation is urgent for the industrial horseshoe crab culture. In this study, β-glucan (G), peptidoglycan (P), and squalene (S) were injected to horseshoe crabs at two concentrations (5 and 10 mg/kg), in order to compare their effects on total hemocyte count (THC), reactive oxygen species (ROS), and non-specific immune enzyme activities. Results showed that the THC, superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were significantly increased by three immunostimulants at different points of time; ROS was significantly increased except at two squalene groups; lysozyme (LZM) and alkaline phosphatase (AKP) activity were increased except at low dose (5 mg/kg) squalene group; malondialdehyde (MDA) activity was decreased in all treatments; and hemocyanin concentration (HC) changed little during the experiment. At the 48th hour, THC, ROS, SOD, CAT, T-AOC, LZM, and AKP activities were significantly higher in the two peptidoglycan groups than those in the control group; the low dose β-glucan and squalene groups showed significantly higher SOD and CAT, but their THC and AKP were not significantly different from those of the control group. In general, all three immunostimulants stimulated the hemolymph parameters of horseshoe crabs, notably, peptidoglycan could significantly increase the THC and enzyme activities, suggesting that peptidoglycan can be developed as an efficient immunostimulant for horseshoe crabs.

BCG Cell Wall Skeleton As a Vaccine Adjuvant Protects Both Infant and Old-Aged Mice from Influenza Virus Infection.

Bacillus Calmette-Guerin (BCG) and the cell wall skeleton (CWS) derived from BCG are known to enhance nonspecific immune activation and anti-cancer immunity; however, their roles as a vaccine adjuvant are largely unknown. Here, we report that BCG-CWS acts as a strong immune adjuvant by promoting the protective immune responses in mouse models with influenza vaccination. The different aged mice immunized with inactivated split vaccine with or without BCG-CWS were challenged with an influenza pandemic virus. When protective immune responses were compared, even a single immunization of adult mice with a BCG-CWS-adjuvanted vaccine showed significantly enhanced humoral immune responses with increased IgG1 and IgG2a isotype antibodies. Importantly, the protective effects by the BCG-CWS adjuvant for influenza vaccination upon humoral and cellular immunogenicity were comparable between infants (6 days and 2 weeks old) and aged (20 months old) mice. Moreover, BCG-CWS dramatically augmented vaccine-mediated protective responses, including decreased viral loads, lung damage, and airway resistance, as well as increased mouse survival, amelioration of weight loss, and proinflammatory cytokine expression in all experimental groups including infant, adults, and old aged mice. We further provided the evidence that the BCG-CWS adjuvant effects were mediated through Toll-like receptors (TLR) 2 and TLR4 signaling pathways. Together, these data suggest that BCG-CWS can be promising as a potential influenza vaccine adjuvant in both young and old aged population through TLR2/4-mediated immune-boosting activities.

Effects of photoperiod on growth, digestive, metabolic and non-special immunity enzymes of Takifugu rubripes larvae

Photoperiod is one of the important environmental factors, which have important effects on the early growth and development, survival, metabolism and immune system of larvae. In the present study, Takifugu rubripes larvae were exposed to four different LED photoperiods: 8 L:16 D, 16 L:8 D, 20 L:4 D and 24 L:0 D from −1 to 30 days post hatching (DPH). We measured growth, activity of pepsin (PPS), lipase (LPS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and non-specific immune enzyme activity of alkaline phosphatase (AKP), and acid phosphate (ACP), superoxide dismutase (SOD), Catalase (CAT), glutathione peroxide (GSH-PX), total antioxidant capacity (T-AOC) at 1, 5, 10, 15, 20, and 30 DPH. The results showed that there was no difference in the effects of photoperiod on the growth within 18 DHP, while 20 L:4 D had a positive effect on the growth of the larvae after 19 DPH. The effect of photoperiod on digestive enzymes did not show obvious regularity. Compared with photoperiod, the changes of some digestive and metabolic enzymes were mainly affected by exogenous food (LPS, ALT, AST changed obviously after feeding Artemia). On the 30 DPH, the AKP of 8 L: 16 D and 24 L: 0 D groups was significantly higher than that of the other two groups, which indicated that 8 L: 16 D and 24 L: 0 D lighting might cause stress to fish body and lead to the increase of AKP. GSH-PX in newly hatched fish at 24 L:0 D was significantly higher than that in other groups. Photoperiod had no significant effect on the enzyme activity of PPS, LDH, ACP, CAT and no obvious pattern was found. Overall, our results suggested that 20 L:4 D promoted larval growth after 19 DPH and shorter photoperiods can be used to save electricity before 18 DPH of Takifugu rubripes larva.

Показники імунореактивності у щурів за умов різних режимів харчування

The research deals with the integral haematological indices such as markers of immunoreactivity and phagocytic activity of neutrophils in animals kept in conditions of a nutrient imbalance. The animals were divided into four experimental groups: I — animals receiving full-value semi-synthetic ration (control group); II — animals receiving low-protein ration (LPR); III — animals receiving high-sucrose diet (HS); IV — animals receiving low-protein/high-sucrose diet (LPR/HS). It has been found that in animals kept in conditions of nutritional protein deficiency there was a disturbance of the specific immune response, as evidenced by a decrease in the immunoreactivity index and an increase in the index of neutrophils and leukocytes ratio. At the same time, no significant changes in the index of blood leukocytes shift and phagocytic activity of neutrophils were found, indicating the preservation of the non-specific immune response activity. However, in animals of this experimental group compensation of endotoxemia and a decrease in the adaptation index were observed, indicating an inhibition of the adaptive mechanisms. Similar changes in the integral haematological indices were observed in animals kept on a high-sucrose ration. It has been shown that animals consuming a low protein/high-sucrose ration have low immunological reactivity, as evidenced by a 3.4-fold decrease in the immunoreactivity index and a 1.5-fold increase in the blood leukocyte shift index, and disturbances in specific immune response (marker is an increase in the neutrophils and lymphocytes ratio), as well as a significant decrease in the phagocytic index, indicating the ineffectiveness of immune reactions involving neutrophils. At the same time, the intensification of the adaptive mechanisms and a three-fold increase in the reactive neutrophil response index indicates the subcompensation stage of endotoxemia. It is concluded that studied integral haematological parameters can be used as additional early diagnostic markers of impaired immunoreactivity and endotoxemia in animals kept in conditions of different protein and sucrose content in the diet.

Evaluation of defatted Hermetia illucens larvae meal for Litopenaeus vannamei : effects on growth performance, nutrition retention, antioxidant and immune response, digestive enzyme activity and hepatic morphology

Defatted black soldier fly (Hermetia illucens) larvae meal (DBSFLM) has been shown an important alternative protein ingredient for fish, but little information is available about the effect of DBSFLM on growth and health of Litopenaeus vannamei. A 56-day feeding trial was conducted to assess the effects of partial replacement of fish meal with DBSFLM on growth performance, body composition, nutrition retention, blood metabolites, antioxidant and immune response, digestive enzyme activities and hepatic morphology of L. vannamei. Six isonitrogenous and isoenergy diets were formulated by replacing 0% (G0), 15% (G15), 30% (G30), 45% (G45), 60% (G60) and 80% (G80) of fish meal with DBSFLM. Each diet was randomly assigned to quadruplicate groups of 40 shrimp per tank. Shrimp were fed three times daily to apparent satiation. Blood samples were collected at the terminal trial to analyse antioxidant and non-specific immune enzyme activities. Hepatopancreas and intestine samples were collected to determine digestive enzyme activities and hepatic morphology. Shrimp fed G80 had lower (p < .05) final body weight, weight gain and specific growth rate, and higher (p < .05) feed conversion ratio than other groups. Crude protein (CP) in the whole body and muscle, coupled with CP and lipid retention of shrimp were decreased (p < .05) as dietary DBSFLM increasing. Shrimp fed G80 had lower (p < .05) serum total cholesterol but higher (p < .05) total antioxidant capacity than other diets, and serum malondialdehyde was lower (p < .05) in shrimp fed G45-G80 than those fed G0-G30. Hepatic and intestinal digestive enzyme activities were not altered by treatments (p > .05). Hepatocytes were shown to have different degrees of vacuolar degeneration, hepatic corpuscle atrophy and starlike lumen lose as observed in G60 and G80. The results demonstrated that up to 60% of fish meal could be replaced by DBSFLM without any adverse effects on growth performance, antioxidant and immune enzyme activities, and digestive enzyme activities of L. vannamei. However, hepatocyte damage was observed when the replacement levels exceeded 60%.

Impact of Diet on Symptoms of the Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), with its key features of abdominal pain and disturbed bowel habit, is thought by both patients and clinicians to be strongly influenced by diet. However, the complexities of diet have made identifying specific food intolerances difficult. Eating disorders can masquerade as IBS and may need specialist treatment. While typical food allergy is readily distinguished from IBS, the mechanisms of gut-specific adverse reactions to food are only just being defined. These may include gut-specific mast cell activation as well as non-specific activation by stressors and certain foods. Visceral hypersensitivity, in some cases mediated by mast cell activation, plays a key part in making otherwise innocuous gut stimuli painful. Rapidly fermented poorly absorbed carbohydrates produce gaseous distension as well as short-chain fatty acids and lowering of colonic pH which may cause symptoms in IBS patients. Limiting intake of these in low FODMAP and related diets has proven popular and apparently successful in many patients. Existing diet, colonic microbiota and their metabolic products may be helpful in predicting who will respond. Wheat intolerance may reflect the fact that wheat is often a major source of dietary FODMAPs. It may also be either a forme fruste of coeliac disease or non-specific immune activation. Wheat exclusion can be successful in some of these patients. More research is needed to fully understand the mechanisms of food intolerances and how to best ameliorate them in a personalised medicine approach to diet in IBS.

Mining for humoral correlates of HIV control and latent reservoir size.

While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific immune activation, ensues and progressively leads to premature immunologic aging. Current biomarkers monitoring immunologic changes encompass generic inflammatory biomarkers, that may also change with other infections or disease states, precluding the antigen-specific monitoring of HIV-infection associated changes in disease. Given our growing appreciation of the significant changes in qualitative and quantitative properties of disease-specific antibodies in HIV infection, we used a systems approach to explore humoral profiles associated with HIV control. We found that HIV-specific antibody profiles diverge by spontaneous control of HIV, treatment status, viral load and reservoir size. Specifically, HIV-specific antibody profiles representative of changes in viral load were largely quantitative, reflected by differential HIV-specific antibody levels and Fc-receptor binding. Conversely, HIV-specific antibody features that tracked with reservoir size exhibited a combination of quantitative and qualitative changes marked by more distinct subclass selection profiles and unique HIV-specific Fc-glycans. Our analyses suggest that HIV-specific antibody Fc-profiles provide antigen-specific resolution on both cell free and cell-associated viral loads, pointing to potentially novel biomarkers to monitor reservoir activity.

Tuberculosis versus COVID-19 Mortality: A New Evidence

BACKGROUND: Coronavirus current pandemic (COVID-19) is the striking subject worldwide hitting countries in an unexplained non-universal pattern. Bacillus Calmette–Guérin (BCG) vaccine was an adopted recent justification depending on its non-specific immune activation properties. Still the problem of post-vaccine short duration of protection needs to be solved. The same protective mechanism was identified in active or latent tuberculosis (TB). For each single patient of active TB, there are about nine cases of asymptomatic latent TB apparently normal individuals living within the community without restrictions carrying benefits of immune activation and involved in re-infection cycles in an excellent example of repeated immunity training sessions of the whole community.&#x0D; AIM: We aimed to asses the correlation between TB burden and COVID-19 mortality in all affected countries having different BCG vaccination policies.&#x0D; METHODS: Publicly available data were extracted for 191 countries including population size, TB estimations, national BCG vaccination policy, the World Health Organization regions and economic classification, and COVID-19 mortality and number of cases. The analysis was performed using Spearman’s correlation test.&#x0D; RESULTS: Significant large negative correlation (−0.539, p &lt; 0.001) was found between TB prevalence and COVID-19 mortality rate worldwide. Medium negative significant correlations were found between TB cases and COVID-19 mortality in the high and lower middle-income countries, and those having current BCG vaccination programs (−0.395, p = 0.001, −0.365, p = 0.015, and −0.476, p &lt; 0.001, respectively).&#x0D; CONCLUSION: Countries with high TB prevalence have higher chances of protection against COVID-19 mortality through the theory of widely distributed natural immune activation within community. Confounders should be assessed separately.

Smooth cordgrass (Spartina alterniflora), a potential food source for Apostichopus japonicus

The sea cucumber (Apostichopus japonicus) is becoming one of the most important fishery resources in Asia. Spartina alterniflora is a common invasive plant in China, that has not been effectively controlled or utilized. Some studies have shown that the organic detritus of S. alterniflora can be used by benthic animals. This study investigated the effects of the addition of S. alterniflora in the diet of juvenile A. japonicus on growth performance, digestive enzyme activity, non-specific immunity and gut microbiota. Powdered S. alterniflora and Sargassum polycystum were mixed in five proportions (0,100, 25,75; 50:50; 75:25; 100:0) along with muddy sediment (60% of total food) to create five different experimental diets for sea cucumbers. The results showed that specific growth rates (SGRs) improved with the addition of S. alterniflora, but did not increased with the increasing proportion of S. alterniflora. The increase in the ratio of S. alterniflora also improved the food conversion efficiency (FCE) of A. japonicus. The cellulase activity was highest in P20 group, which is a mixture of 20% S. alterniflora, 20% S. polycystum and 60% muddy sediment. Non-specific immune enzyme activity was not altered by the addition of S. alterniflora. In addition, the addition of S. alterniflora reduced the abundance of pathogenic bacteria and increased the abundance of bacteria associated with the degradation of high-molecular carbohydrates. The results of this study indicated that S. alterniflora could be a potential food source for A. japonicus and might be beneficial to A. japonicus growth. The findings of this study are important for the development of suitable feed for A. japonicus and the management and utilization of invasive plants.

Antioxidant capacity, non-specific immunity, histopathological analysis and immune-related genes expression in Nile tilapia Oreochromis niloticus infected with Aeromonas schubertii

Aeromonas schubertii is a conditional pathogen widely distributed in aquatic environments, yet it was only recently reported as a causative pathogen in fish. This study investigated antioxidant capacity, non-specific immunity, histopathology and immune-related gene expression profiles in Nile tilapia Oreochromis niloticus injected with A. schubertii. The results show that A. schubertii infection stimulated the activation of antioxidant activity and non-specific immunity in Nile tilapia. Histopathological analysis revealed that inflammation existed in the liver, spleen, head kidney, brain and intestine of the infected fish. Quantitative real-time PCR was performed to measure mRNA expression levels of six immune-related genes (interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, transforming growth factor beta, interleukin-10 and heat shock protein 70) in the intestine and head kidney at different timepoints after experimental infection. The results demonstrated clear transcriptional activation of these immune-related genes in the intestine and head-kidney tissues. To our knowledge, this is the first study to investigate the host response to A. schubertii infection in a fish. These results will contribute to further understanding of the pathogenesis and host defense system in fishes following infection with A. schubertii.

Racial differences in development of immune-related adverse events.

e15148 Background: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) are caused by non-specific immune system activation and develop in 30-70% of patients. The goal of this study is to examine the association of race with the development of irAEs secondary to ICIs as autoimmune diseases generally exhibit racial differences. Methods: A retrospective chart review was done using University of Louisville pharmacy database. Patients with solid cancers who received ICIs between Jan 2016 to June 2019 were included. IrAEs were identified through the review of electronic medical records. Descriptive analysis evaluated the incidence and severity of irAEs. Multivariable logistic regression was used to calculate standardized incidence of irAEs among Whites and African Americans. Results: A total of 476 patients were included in this study. The mean age was 61 years, 57% were males and 89.7% were whites. A majority of patients had melanoma (50%). The remainder of the dataset included lung (33.4%), gastrointestinal (7.4%), head &amp; neck (4.8%), breast (2.5%) and genitourinary (1.9%) cancers. ICIs included single agent anti-PD-1 (74.8%), single agent anti-PD-L1 (9.4%), combination anti-CTLA-4 with anti-PD-1 (7.1%). Some patients were also treated with &gt; 1 ICI as subsequent therapy (8.6%). Overall, the rate of irAEs was 44.3% with 33.8% grade 1-2 and 12.4% grade 3-4 irAEs. There was no difference in development of any grade irAEs in Whites as compared to African Americans after adjusting for age, sex, cancer type and ICIs (44.3% vs 44.2%; OR: 0.99, 95% CI: 0.50 – 1.97; p = 0.99). There was also no difference in development of grade 3-4 irAEs in whites as compared to African Americans (12.8% vs 14.5%; OR: 1.16, 95% CI: 0.43 – 3.12; p = 0.75). Conclusions: In this study, we found no racial difference in the development of irAEs between Whites and African Americans. This is in contrast to general autoimmune diseases which exhibit racial differences with higher prevalence among African Americans compared to Whites. We will continue to accrue patients to this study as larger sample size is needed to confirm these findings.