Plasma Antibody Levels Research Articles

Early antibody responses to lipid antigens in red deer infected with Mycobacterium bovis

The problem: Early and rapid diagnosis of bovine tuberculosis remains an issue of great interest. Aim: The aim of this study was to evaluate the use of synthetic lipid antigens for diagnosis of tuberculosis in red deer (Cervus elaphus). The proposition: Synthetic mycolic acid derivatives, identical to components of mycobacterial cells, bind to antibodies to lipids produced in active human tuberculosis. Experimental infection studies in red deer (Cervus elaphus) allow the evaluation of such antigens for the serodiagnosis of bovine tuberculosis. Results: Antibody levels in plasma from deer experimentally infected with Mycobacterium bovis were evaluated in ELISA using synthetic antigens based on several classes of mycolic acid, using protein G as conjugate. All antigens gave significantly increased responses 60 days post-infection, when all animals had active disease. A significantly increased response was also observed with four antigens 15 days after infection. Conclusion: ELISA using synthetic lipid antigens not only detects antibodies in the plasma of deer experimentally infected with M. bovis, but a strong response occurs early in the infection. With a full analysis of responses with naturally infected animals, this may offer a useful supplement to current diagnostic methods.

Association between COVID-19 convalescent plasma antibody levels and COVID-19 outcomes stratified by clinical status at presentation

BackgroundThere is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.MethodsThe study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as ‘dose’ of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation.ResultsA total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28).ConclusionHigher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

The Use of the Neoglycolipid-Based Oligosaccharide Microarray System in the Diagnosis of Endometriosis - Preliminary Study.

Endometriosis presents diagnostic challenges, and there is a need for developing novel biomarkers with satisfactory specificity and sensitivity. Glycomics, exploring glycosylation changes in glycoproteins, offers potential solutions. The aim of this study was to analyze the carbohydrate-binding properties of IgG and IgM antibodies in the plasma and peritoneal fluid samples and to identify any differences in the presence and the specificities of anti-carbohydrate antibodies in the endometriosis patient and the controls. Multicenter study was conducted in Poland between 2018 and 2019. Plasma and peritoneal fluid samples were collected from women undergoing laparoscopic surgery. Endometriosis patients (n=8) and controls (n=8), matched for cycle phase and disease stage, were selected. The neoglycolipid-based oligosaccharide microarray system was used to investigate IgG and IgM antibody binding properties to glycan-related probes in biological materials. In peritoneal fluid samples, IgM binding to the following probes was significantly higher in endometriosis: GSC-915-4 (new), LNFP-I, NeuAcα-(6')LNnO (F1), B-like decaosylceramide, log10(GM1-penta), and log10(GSC-915-5). In a control group higher IgG binding to log10(Orsay-5-AO) was observed. In plasma samples, endometriosis showed higher IgG binding to log10(NeuAcα-(6')LNnO (F1)) and lower IgG binding to Gal2GlcNAc(1-3)-AO. After Benjamin-Hochberg correction, differences were not significant. Effect sizes highlighted some glycan probes in both plasma and peritoneal fluid. Strong correlations were observed among binding to certain glycan probes. This preliminary study suggests glycomics' potential contribution to endometriosis diagnosis and understanding of its pathophysiology. Neoglycolipid-based microarrays hold promise for non-invasive endometriosis diagnostic tools. Further investigations with larger cohorts are warranted to validate these findings and explore potential correlations with antibody levels in plasma and peritoneal fluid. Glycomics emerges as a valuable diagnostic asset in endometriosis research.

Analysis of related factors of plasma antibody levels in patients with severe and critical COVID-19

Coronavirus disease 2019 (COVID-19) continues to impact global public health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become less virulent as it mutates, prompting China to ease restrictions at the end of 2022. With the complete reopening, a surge in COVID-19 cases has ensued. Therefore, we conducted a study to explore the correlation between plasma antibody levels and baseline conditions or clinical outcomes in severe and critical patients. We collected the basic information of 79 included patients. Enzyme-linked immunosorbent assay (ELISA) tests were performed on plasma samples. The receptor-binding domain (RBD) IgG antibody level of the mild group was significantly higher than that of the severe/critical group (P = 0.00049). And in the severe/critical group, there existed an association between plasma antibody levels and age (P < 0.001, r = − 0.471), as well as plasma antibody levels and vaccination status (P = 0.00147, eta2 = 0.211). Besides, the level of plasma antibody seemed to be moderately correlated with the age, indicating the need for heightened attention to infections in the elderly. And plasma antibody levels were strongly associated with vaccination status in the severe/critical patients.

Associations between Plasma Antibody Levels against Porphyromonas gingivalis and Atrial Fibrillation among Community-Dwelling Older Individuals in Japan: A Cross-Sectional Study.

To investigate the association between plasma antibody levels against Porphyromonas gingivalis (PG) and atrial fibrillation (AF) history in community-dwelling older individuals in Japan. This study was a subset of the Uonuma cohort study, including 3091 participants aged 60-79 years. Data were collected, including AF history as a dependent variable, plasma immunoglobulin G antibody levels against PG as an independent variable, and previously reported AF risk factors and demographic information as covariates. The median age of the participants was 69 years. Of the 3091 participants, 1411 (45.6%) were men, and 56 (1.8%) had an AF history. AF prevalence was significantly higher in participants with higher antibody levels against PG than in those with lower antibody levels (3.0% vs 1.4%; p = 0.005). Multivariable logistic regression analysis showed that participants with higher antibody levels against PG had twofold higher odds of having AF (odds ratio = 2.13; 95% confidence interval = 1.23-3.69). Restricted cubic spline analysis indicated a nonlinear relationship between antibody levels against PG and AF history. Plasma antibody levels against PG were associated with AF history in community-dwelling older individuals in Japan.

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; the severity of symptoms and mortality are higher in men than in women, exhibiting an evident sexual dimorphism in the immune response; therefore, the contribution of 17β-estradiol and testosterone to this phenomenon has been studied. Both hormones differentially affect several aspects of innate and adaptive immunity. Dehydroepiandrosterone (DHEA) is the precursor of both hormones and is the sexual steroid in higher concentrations in humans, with immunomodulatory properties in different parasitic diseases; however, the involvement of DHEA in this sexual dimorphism has not been studied. In the case of malaria, the only information is that higher levels of DHEA are associated with reduced Plasmodium falciparum parasitemia. Therefore, this work aims to analyze the DHEA contribution to the sexual dimorphism of the immune response in malaria. We assessed the effect of modifying the concentration of DHEA on parasitemia, the number of immune cells in the spleen, cytokines, and antibody levels in plasma of CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). DHEA differentially affected the immune response in males and females: it decreased IFN-γ, IL-2 and IL-4 concentrations only in females, whereas in gonadectomized males, it increased IgG2a and IgG3 antibodies. The results presented here show that DHEA modulates the immune response against Plasmodium differently in each sex, which helps to explain the sexual dimorphism present in malaria.

Differential cellular and humoral immune responses in immunocompromised individuals following multiple SARS-CoV-2 vaccinations.

The heterogeneity of the immunocompromised population means some individuals may exhibit variable, weak or reduced vaccine-induced immune responses, leaving them poorly protected from COVID-19 disease despite receiving multiple SARS-CoV-2 vaccinations. There is conflicting data on the immunogenicity elicited by multiple vaccinations in immunocompromised groups. The aim of this study was to measure both humoral and cellular vaccine-induced immunity in several immunocompromised cohorts and to compare them to immunocompetent controls. Cytokine release in peptide-stimulated whole blood, and neutralising antibody and baseline SARS-CoV-2 spike-specific IgG levels in plasma were measured in rheumatology patients (n=29), renal transplant recipients (n=46), people living with HIV (PLWH) (n=27) and immunocompetent participants (n=64) post third or fourth vaccination from just one blood sample. Cytokines were measured by ELISA and multiplex array. Neutralising antibody levels in plasma were determined by a 50% neutralising antibody titre assay and SARS-CoV-2 spike specific IgG levels were quantified by ELISA. In infection negative donors, IFN-γ, IL-2 and neutralising antibody levels were significantly reduced in rheumatology patients (p=0.0014, p=0.0415, p=0.0319, respectively) and renal transplant recipients (p<0.0001, p=0.0005, p<0.0001, respectively) compared to immunocompetent controls, with IgG antibody responses similarly affected. Conversely, cellular and humoral immune responses were not impaired in PLWH, or between individuals from all groups with previous SARS-CoV-2 infections. These results suggest that specific subgroups within immunocompromised cohorts could benefit from distinct, personalised immunisation or treatment strategies. Identification of vaccine non-responders could be critical to protect those most at risk.

Saliva and Plasma Antibody Levels in Children and Adolescents After Primary Infection With Omicron Variants of SARS-CoV-2 Infection in Germany

This cross-sectional study evaluates IgG antibody levels in children and adolescents in Germany following SARS-CoV-2 infection.

Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection.

There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.

Detection of Plasma Antibodies Against CD25-Derived Peptide Antigens in Bladder Cancer.

Altered anti-CD25 antibody levels in plasma have been observed in patients with various solid malignancies. The present study aimed to determine whether circulating anti-CD25 antibody levels were altered in bladder cancer (BC). An enzyme-linked immunosorbent assay was developed in-house to detect plasma IgG antibodies against three CD25-derived linear peptide antigens in 132 patients with BC and 120 control subjects. The Mann-Whitney U-test indicated that the plasma levels of anti-CD25a (Z = -10.11, p < 0.001), anti-CD25b (Z = -12.79, p < 0.001), and anti-CD25c IgG (Z = -11.95, p < 0.001) were significantly lower in BC patients than in the control group. Further analysis indicated that the plasma levels of anti-CD25a IgG antibody were stage-dependent and associated with different postoperative histological grades (U = 977.5, p = 0.003). The receiver operating characteristic curve analysis showed that the area under the ROC curve (AUC) was 0.869 for anti-CD25a IgG (95%, 0.825 - 0.913), 0.967 for anti-CD25b IgG (95%, 0.945 - 0.988), and 0.936 for anti-CD25c IgG (95%, 0.905 - 0.967), with a sensitivity of 91.3% for the anti-CD25a IgG assay, 98.8% for the anti-CD25b IgG assay, and 96.7% for the anti-CD25c IgG assay, against a specificity of 95%. The present study suggests that circulating anti-CD25 IgG may have a potential predictive value for clinical staging and histological grading of BC.

Flavobacterium psychrophilum: Response of Vaccinated Large Rainbow Trout to Different Strains.

Although Flavobacterium psychrophilum is recognized as the causative pathogen of rainbow trout fry syndrome (RTFS), often resulting in high fry mortality, it is also responsible for bacterial cold water disease (BCWD) in large and older rainbow trout (Oncorhynchus mykiss). These older fish do not experience high mortality, but sustain, through the shedding of bacteria, a constant infection pressure at farm level, which exposes fry to an unnecessary infection risk. We have produced and assessed the immunogenicity of an experimental injection BCWD vaccine, which may be used to decrease the shedding of bacteria from older fish. A total of 800 fish were i.p.-injected: 200 fish received the bacterin with adjuvant, 200 fish received the bacterin alone, 200 fish received adjuvant alone and 200 fish were injected with physiological saline. Blood samples were taken at day 0 and at three different time points (4, 8 and 14 weeks) post-vaccination. Plasma antibody levels were measured by ELISA for reactivity against both the homologous F. psychrophilum vaccine strain (serotype Fd) and heterologous strains (serotype Th). Significantly elevated antibody titers were found against all serotypes in vaccinated fish. Welfare parameters associated with the vaccination process were evaluated by analyzing trout plasma samples for six different biochemical parameters, but no adverse effects associated with injection were indicated. The study suggests that an injection vaccine containing formalin-inactivated whole cells of F. psychrophilum (serotype Fd), adjuvanted with FIA, may also induce protection against heterologous strains. We advocate for, as the next step, the performance of field trials evaluating if the vaccination of older rainbow trout will (1) reduce the infection pressure in farms, (2) elevate the general health level in all groups and (3) minimize F. psychrophilum infection in fry at farm level. This may reduce the need for the administration of antibiotics in all age classes.

A Study of Plasma Anti-Thyroperoxidase Antibodies and Anti-Thyroglobulin Antibodies in patients with Hypothyroidism

Aim: To determine the plasma anti-thyroperoxidase antibodies (Anti-TPO) and anti-thyroglobulin antibodies (ATG) in hypothyroid patients Methods: This study was carried out at Arif Clinical Laboratory and Diagnostic center, Lahore. Samples were collected from 750 patients diagnosed with hypothyroidism. The blood samples were analyzed for the levels of anti-thyroperoxidase antibodies (n=450) and anti-thyroglobulin (n=300) antibodies. Depending upon the serum levels of these antibodies, the obtained titerswere categorized as normal, mildly elevated, moderately elevated and highly elevated. Duration of study was around08 months, extending from November 2021 to May 2022. Results: Among the total 750 patients with hypothyroidism, 450 were estimated for Anti-TPO antibodies, whereas, 400 patients were analyzed ATG antibodies. Anti-TPO antibodies were normal in 191 patients (42.44%) and high levels were observed in 259 patients (57.55%), indicating a greater role of these antibodies in the causation of hypothyroidism. In contrast, among the 300 patients analyzed for ATG antibodies, 213 patients had normal levels (71%), while 87 has high plasma levels of these antibodies (29%) Practical Implications: Current study provides an insight into the more frequent incidence of Anti-TPO antibodies, thus indicating its more crucial role in causing hypothyroidism in the given population. Therefore, estimation of these autoantibodies earlier in the disease can serve as better indicators of the severity and response to treatment, compared with Anti-TGB antibodies, which are present less frequently in patients with hypothyroidism Conclusion: Anti-TPO antibodies were found to be high in 57.55% patients (n=450) with hypothyroidism, indicating its greater role in the causation of hypothyroidism, whereas, ATG were high in only 29% patients (n=300). The results stress the need to evaluate all patients of hypothyroidism with plasma antibody levels for early diagnosis and a prompt management plan. Keywords: anti-thyroglobulin, anti-thyroperoxidase, hypothyroidism, Thyroxine, Triiodothyronine

Preclinical development of ZED8, an 89Zr immuno-PET reagent for monitoring tumor CD8 status in patients undergoing cancer immunotherapy.

ZED8 is a novel monovalent antibody labeled with zirconium-89 for the molecular imaging of CD8. This work describes nonclinical studies performed in part to provide rationale for and to inform expectations in the early clinical development of ZED8, such as in the studies outlined in clinical trial registry NCT04029181 [1]. Surface plasmon resonance, X-ray crystallography, and flow cytometry were used to characterize the ZED8-CD8 binding interaction, its specificity, and its impact on T cell function. Immuno-PET with ZED8 was assessed in huCD8+ tumor-bearing mice and in non-human primates. Plasma antibody levels were measured by ELISA to determine pharmacokinetic parameters, and OLINDA 1.0 was used to estimate radiation dosimetry from image-derived biodistribution data. ZED8 selectively binds to human CD8α at a binding site approximately 9Å from that of MHCI making mutual interference unlikely. The equilibrium dissociation constant (KD) is 5nM. ZED8 binds to cynomolgus CD8 with reduced affinity (66nM) but it has no measurable affinity for rat or mouse CD8. In a series of lymphoma xenografts, ZED8 imaging was able to identify different CD8 levels concordant with flow cytometry. In cynomolgus monkeyswith tool compound89Zr-aCD8v17, lymph nodes were conspicuous by imaging 24h post-injection, and the pharmacokinetics suggested a flat-fixed first-in-human dose of 4mg per subject. The whole-body effective dose for an adult human was estimated to be 0.48mSv/MBq, comparable to existing 89Zr immuno-PET reagents. 89Zr immuno-PET with ZED8 appears to be a promising biomarker of tissue CD8 levels suitable for clinical evaluation in cancer patients eligible for immunotherapy.

A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL).

Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.

Decreased serum interleukin-41/Metrnl levels in patients with Graves' disease.

BackgroundInterleukin (IL)‐41, also known as Metrnl, is a novel immunomodulatory cytokine, which is involved in the pathogenesis of many inflammatory and metabolic diseases, but its role in thyroid autoimmune diseases is not clear. The aim of this study was to evaluate the serum IL‐41 levels in patients with Graves' disease (GD) and its relationship with GD.MethodsThis study included a total of 49 GD patients and 47 age‐ and sex‐matched healthy individuals. All baseline data were obtained by physical examination. Free triiodothyronine 3 (FT3), free triiodothyronine 4 (FT4), thyroid‐stimulating hormone (TSH), anti‐thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) levels in plasma of GD patients were measured by chemiluminescence. The high‐sensitivity C‐reactive protein (CRP) and white blood cell count (WBC) were detected using automated biochemical analyzer. Serum IL‐41 levels were measured by enzyme‐linked immunosorbent assay.ResultsSerum IL‐41 levels in patients with GD were significantly lower than those in healthy controls (201.0 vs. 260.8 pg/mL, p < 0.05). There was a significant positive correlation between IL‐41 level and CRP (r = 0.2947, p = 0.0385) and WBC (r = 0.4104, p = 0.0034) in GD patients. CRP was positively correlated with TRAb (r = 0.2874, p = 0.0452) and TSH (r = 0.3651, p = 0.0099) levels in GD patients.ConclusionsThis study demonstrates that GD patients have decreased serum IL‐41 levels, and IL‐41 plays a potential role in abnormal immune response of GD patients.

Antibiotic perturbation of gut bacteria does not significantly alter host responses to ocular disease in a songbird species.

Bacterial communities in and on wild hosts are increasingly appreciated for their importance in host health. Through both direct and indirect interactions, bacteria lining vertebrate gut mucosa provide hosts protection against infectious pathogens, sometimes even in distal body regions through immune regulation. In house finches (Haemorhous mexicanus), the bacterial pathogen Mycoplasma gallisepticum (MG) causes conjunctivitis, with ocular inflammation mediated by pro- and anti-inflammatory cytokines and infection triggering MG-specific antibodies. Here, we tested the role of gut bacteria in host responses to MG by using oral antibiotics to perturb bacteria in the gut of captive house finches prior to experimental inoculation with MG. We found no clear support for an impact of gut bacterial disruption on conjunctival pathology, MG load, or plasma antibody levels. However, there was a non-significant trend for birds with intact gut communities to have greater conjunctival pathology, suggesting a possible impact of gut bacteria on pro-inflammatory cytokine stimulation. Using 16S bacterial rRNA amplicon sequencing, we found dramatic differences in cloacal bacterial community composition between captive, wild-caught house finches in our experiment and free-living finches from the same population, with lower bacterial richness and core communities composed of fewer genera in captive finches. We hypothesize that captivity may have affected the strength of results in this experiment, necessitating further study with this consideration. The abundance of anthropogenic impacts on wildlife and their bacterial communities, alongside the emergence and spread of infectious diseases, highlights the importance of studies addressing the role of commensal bacteria in health and disease, and the consequences of gut bacterial shifts on wild hosts.

Effect of convalescent plasma therapy on mortality in moderate-to-severely Ill COVID-19 patients

IntroductionThe role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. MethodsThis retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. ResultsOf the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. ConclusionsWe report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it isprematurely shelved.

Feasibility of identifying plasma donors with high measles neutralizing antibody concentrations for the use of producing a measles hyperimmune globulin for postexposure prophylaxis

Immune globulin (IG) is administered as measles postexposure prophylaxis (PEP) in people with primary immunodeficiency disorders or individuals not eligible for live virus vaccination. However, measles virus (MeV) neutralizing antibody (nAb) levels in plasma for fractionation and IG products fractionated thereof have declined. Here, the feasibility of producing a measles hyperimmune globulin (HIG) for PEP of high-risk individuals was investigated. Plasma samples (n = 384) were selected based on donor self-identification for previous MeV infection or vaccination, to determine the MeV-nAb content and compare it to the potency of plasma pools (n = 13) from the current IG manufacture. Convalescent donors have higher mean MeV-nAb concentrations (3.9 IU/mL) than vaccinated donors (2.5 IU/mL), as previously reported. However, their selection would only result in a 1.4-fold elevated nAb concentration compared to current plasma pools, which is not sufficient for HIG production. Interestingly, thirty-two donors (8%) had a MeV-nAb concentration of ≥ 8 IU/mL. The selective use of these plasma donations would result in sixfold higher plasma pool concentrations, which should permit the manufacture of the measles HIG. Further, the longitudinal analysis of a subset of individuals who repeatedly donated plasma at a high frequency revealed only a minor decline (~ 30%) of MeV-nAb levels. Repeat donations of such high-potency donors would thus facilitate the production of the measles HIG. Due to its markedly raised MeV-nAb concentration compared to standard IG, such preparation could significantly shorten infusion time and thus improve the treatment experience for both physicians and patients, especially infants.

Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients

BackgroundBone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the influence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.ResultsWe quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4+ T cells using flow cytometry and genotyped two intronic single nucleotide polymorphisms (SNPs) rs919267 and rs919266 together with one SNP rs9576 located in the 3’ untranslated region (UTR) of bst-2 gene using TaqMan assays from HIV-1 uninfected and infected participants. Subsequently, we determined the ability of plasma antibody levels to mediate antibody-dependent cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4+ T cells were lower in HIV-1 infected compared to uninfected participants (p = 0.075 and p < 0.001, respectively). rs919267CT (p = 0.042) and rs919267TT (p = 0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 counts, (p = 0.003), gp120-IgG1 (p = 0.040), gp120-IgG3 (p = 0.016) levels but higher viral loads (p = 0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p = 0.046), CD4 counts (p = 0.001), gp120-IgG1 levels (p = 0.033) but higher plasma viral loads (p = 0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p = 0.027), CD4 counts (p = 0.079), gp120-IgG1 (p = 0.009), gp120-IgG3 (p = 0.039) levels but with lower viral loads (p = 0.037).ConclusionOur findings show that bst-2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but not p24-IgG levels, ADCC and ADCP activity.Graphical