IgG Concentrations Research Articles

Serum IgG Antibody against Helicobacter pylori and the CagA-VacA s1 Genotype as a Predictor of Gastric Cancer Development: A Case-control Study

Helicobacter pylori (H. pylori)-induced inflammation increases the risk of developing various upper gastrointestinal conditions which may progress to gastric cancer (CA). Early prediction and detection of infection are crucial for reducing cancer-induced mortality rates. The present case-control study aimed to investigate the combination of serum and molecular markers and H. pylori-associated gastro-duodenal conditions as risk factors for predicting CA development in dyspeptic patients. Consecutive gastric biopsies and blood samples were collected from 100 adult dyspeptic patients. Serum IgG antibody levels against H. pylori were determined, and receiver operating characteristic (ROC) analysis was performed. The expression of the virulence genes cagA and vacA was evaluated by polymerase chain reaction (PCR). A significant association was reported between the disease condition and the status of several risk factors, such as family history, serum IgG antibody concentration, and the virulence genes cagA and vacA. Among the 71 H. pylori-positive patients, 35.2% (25/71) had CA. Both cagA and vacA genes were found in 46 out of 71 (64.7%) patients, and 92% (23/25) of CA patients carried the cagA+vacA s1 gene. ROC analysis of the serum IgG concentrations revealed AUC values of 0.81 and 0.78 for differentiating patients with non-ulcer dyspepsia from those with ulceration/inflammation and CA, respectively. The concordance between the IgG-positive and PCR-positive patients was 84% (k value=0.41). Patients who had a family history of CA with an increased serum IgG concentration and the presence of H. pylori cagA-vacA s1 genotypes may be considered strong predictors of future development of gastric pathologies, including CA.

The effect of BCG revaccination on the response to unrelated vaccines in urban Ugandan adolescents (POPVAC C): an open-label, randomised controlled trial

Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren. We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete. Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group. We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

Changes in Immunoglobulins G and A in the Saliva and Serum of Horses with Equine Gastric Ulcer Syndrome (EGUS) and Their Relationship with Other Immune and Redox Status Biomarkers

Equine Gastric Ulcer Syndrome (EGUS) is a widespread disease with a very high prevalence and importance in horses. It includes two conditions: Equine squamous gastric disease (ESGD), linked to acid disturbances, and Equine Glandular Gastric Disease (EGGD), associated with inflammation and immune system issues. In saliva, increased levels of immunological markers have been observed in this disease, indicating immune system involvement. In addition, changes in biomarkers of oxidative stress have been described. In horses, IgG and IgA are proteins that appear in saliva and serum and are considered to be the major proteins in specific immunity; however, their levels in horses with EGUS have not been previously studied. This report aims to evaluate IgG and IgA concentrations in the saliva and serum of horses with EGUS, measured by automated assays, and compare them with other biomarkers of the immune and oxidative stress system. This work validated the IgG and IgA assays in saliva and showed that IgA significantly increased in the saliva of horses with EGUS. When the correlation between IgG and IgA and other biomarkers of immune system issues and oxidative stress such as ADA, S100 A8-A9 (calprotectin), S100 A12 (calgranulin), uric acid, FRAS, and AOPP was studied, IgA in saliva showed a significant moderate correlation with adenosine deaminase, indicating its possible involvement in the immune reaction occurring in EGUS.

Interrogating post-transplant donor HLA-specific antibody characteristics and effector functions using clinical bead assays

Single antigen bead (SAB) assays are the most common and sensitive method used to detect and monitor post-transplant donor specific HLA antibodies (DSA). However, a direct comparison across traditional and modified SAB assays to improve routine DSA monitoring using pre-treated IgG sera to eliminate interference has not been performed. We performed a technical comparison of 251 post-transplant DSA from n = 91 serum samples tested neat (pre-treated, undiluted), at a single 1:16 dilution, in the C1q bead assay, and for IgG subclasses (IgG1, IgG2, IgG3, IgG4) with IgG-enriched sera. We found that DSAs that are detectable by 1:16 dilution and/or C1q are associated with higher IgG MFI values and results could be predicted by testing neat sera. DSA detected at 1:16 dilution correlated with >7000 IgG MFI in neat sera and identified DSA that exceeded the SAB linear range for semiquantitative measurements. C1q positive DSA correlated with >15,000 IgG MFI in neat sera. C1q binding correlated most strongly with total IgG MFI (Spearman r = 0.82, p = 0.002) and not specific subclasses, demonstrating that DSA C1q binding capacity in this cohort is driven by HLA-specific IgG concentration. Evaluation of engineered pan-HLA class I-specific human IgG1 and IgG2 subclass monoclonal antibodies by SAB C1q and C3d assays revealed that IgG2 antibodies can bind complement at higher concentrations. The strengths and limitations of modified SAB assays must be considered to optimize efficient testing and accurate clinical interpretation.

Comparative analysis of the parameters of local immunity of oral fluid and the duration of the course in children with systemic lupus erythematosus, juvenile scleroderma, juvenile dermatomyositis, juvenile idiopathic arthritis and systemic vasculitis

Immunoglobulins are considered to be the main factor of specific antimicrobial protection of oral tissues.The study was conducted on the basis of the University Children’s Clinical Hospital of the I.M. Sechenov First Moscow State Medical University of the N.F. Filatov Clinical Institute of Child Health, in the Department of Rheumatology. The study involved 316 children, with diseases: systemic lupus erythematosus (SLE), juvenile dermatomyositis (YDM), juvenile limited scleroderma (YOSD), juvenile systemic scleroderma (YSSD), juvenile idiopathic arthritis (JIA), systemic vasculitis (SV) and Behcet’s disease (BB) and were divided into age groups according to the duration of the course of the underlying disease. The analysis of the results revealed a decrease in the content of IgG, IgA, sIgA in saliva in children with rheumatic diseases in all age groups compared with the control group (children without somatic diseases). With the duration of the course of the disease up to 2 years, the most pronounced decrease in the content of IgG, IgA, sIgA in saliva was revealed, more than 4–10 times (p<0.05), and with a duration of more than 2 years, a decrease of 2–3 times (p<0.01), compared with the control group. The deficiency of these immunoglobulins shows that in children with rheumatic diseases, regardless of the nosology, there is a violation of the local immunity of the oral cavity, especially at the onset of the underlying disease (in groups up to 2 years of the duration of the course of the underlying disease), with pronounced autoimmune inflammation of tissues and blood vessels, and this is also facilitated by the reception, during this period of shock doses of glucocorticosteroids, cytostatics, immunosuppressors, which leads to severe inflammatory processes of the oral mucosa, periodontal and hard tissues of the teeth.

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

The effect of 12-week high-dose Colostrum Bovinum supplementation on immunological, hematological and biochemical markers in endurance athletes: a randomized crossover placebo-controlled study.

Bovine colostrum (COL) is assumed to be one of the strongest natural immune stimulants. Regular ingestion of COL may contribute to improved immune response in athletes exposed to high training loads. Twenty-eight endurance-trained males aged 31.1 ± 10.2 years (body mass 81.9 ± 9.0kg; height 1.82 ± 0.06m) completed this randomized double-blind placebo(PLA)-controlled crossover study aimed at investigating the effect of 12-week COL supplementation (25gCOL·day-1) on resting (REST), exercise-induced (POST-EX), and short-term post-exercise recovery (REC; 1h after test exercise) changes in selected saliva and blood immunoglobulins (Ig), white blood cell (WBC) count and differential; as well as blood hematological, nutritional status and muscle damage indices. The protocol assumed 4 study visits - before/after supplementation with COL (COLPRE and COLPOST ) and PLA (PLAPRE and PLAPOST ). During testing sessions, incremental rowing test to exhaustion and swimming-specific performance test were introduced as exercise stimuli. At COLPOST visit the secretory IgA (SIgA) concentration in saliva was significantly higher at POST-EX and REC compared to REST (p<0.05). COL supplementation had no effect on blood IgA, IgE, IgD, IgG, and IgM concentrations. Furthermore, after COL supplementation decrease of hematocrit at REC (p<0.05) was revealed. 12-week supplementation with 25 gCOL·day-1 in endurance-trained male athletes resulted in a favorable increase in post-exercise concentration of salivary SIgA. COL seems to be a potential stimulator of local immune defense after exercise-induced homeostasis disturbances. Nevertheless, the lack of effect on blood markers indicates the need for further research in the area of mechanisms underlying the effect of the supposed COL immunological capacity.

Cross-reactivity between dengue virus and SARS-CoV-2 antibodies: Confirmation study using specimens from dengue-infected patients before the COVID-19 pandemic

BackgroundThe simultaneous occurrence of the COVID-19 pandemic and a dengue outbreak has posed significant challenges for governments and medical personnel in dengue-endemic countries like Indonesia. Several studies in dengue-endemic countries have reported cases of misdiagnosis between COVID-19 and dengue. Therefore, it is crucial to evaluate the potential cross-reactivity between SARS-CoV-2 antibodies and dengue. MethodsThis study aimed to confirm the serological cross-reaction between dengue virus and SARS-CoV-2 in Surabaya, East Java, which is a highly dengue-endemic city in Indonesia. In total, 238 serum samples with confirmed dengue that were collected before the emergence of COVID-19 were tested to detect the presence of reacting IgG and IgM antibodies (Abs) against SARS-CoV-2 via a rapid detection test (RDT) and enzyme-linked immunosorbent assay (ELISA). Samples from patients with dengue infection collected during the pandemic, from healthy volunteers predating the pandemic, and from patients with COVID-19 were used for comparison. Results and conclusionFew (6.7 %) of the pre-COVID-19 dengue Ab-positive serum samples showed reactive on SARS-CoV-2 in the RDT, with significantly lower IgG and IgM levels detected in ELISA compared with the dengue samples collected during the pandemic and the COVID-19 samples (P < 0.005). A comparable anti-SARS-CoV-2 IgG concentration was observed in the pre-COVID-19 dengue samples and healthy volunteers (P = 0.56), which also indicated other possibilities. In conclusion, our results suggested a low risk of cross-reactivity between dengue virus and SARS-CoV-2. However, they highlighted the need for caution when using and interpreting data obtained stemming from serological methods, to prevent false-positive results. Further studies are needed to evaluate the cross-reactivity between dengue virus, SARS-CoV-2, and other common human pathogens, as well as its effect on the serosurveys, treatment of these diseases, or vaccine efficacy.

COVID-19 Vaccine-induced antibody response to BNT162b2 mRNA in frontline healthcare workers

The emergence of SARS-CoV-2, the virus causing COVID-19, has resulted in a pandemic that has disrupted all sectors of society. Less than a year after the sequencing of the virus’s genome, emergency use authorization for the BNT162b2 vaccine was requested. The aim of this study was to evaluate the response to the BNT162b2-mRNA COVID-19 vaccine in frontline workers from two hospitals in Colombia. Nasopharyngeal swabs were collected for the molecular detection of SARS-CoV-2 using real-time PCR, and blood samples were taken to assess seroconversion using qualitative and quantitative IgA, IgG, and IgM test kits. The study was conducted at a high-complexity healthcare institution in Bucaramanga, Colombia. 245 people were included in the first round and 129 in the second. SARS-CoV-2 molecular tests were conducted by RT-qPCR, and peripheral blood samples were collected to measure IgG, IgM, and IgA. The main outcome was to establish natural infection and the antibody response induced by the vaccine. The entire population was tested at two fixed times with RT-PCR tests and antibody level measurements approximately 4 and 8 months after receiving the second vaccine dose. 62 (25.3%) and 35 (14.3%) participants had a history of positive PCR in the first and second rounds, respectively. All positive cases showed elevated levels of all immunoglobulins, especially IgG. The average concentrations of IgA, IgM, and IgG at 90 days were 1149.5 U/mL (95% CI 828.2-1470.9); 320.3 U/mL (95% CI 218.4-422.3); and 9277.3 U/mL (95% CI 8989.2-9565.3). Frontline healthcare workers showed an adequate response to the BNT162b2 mRNA vaccine.

Immunogenicity and Determinants of Antibody Response to the BNT162b2 mRNA Vaccine: A Longitudinal Study in a Cohort of People Living with HIV

Background: The COVID-19 pandemic posed significant challenges worldwide, with SARS-CoV-2 vaccines critical in reducing morbidity and mortality. This study evaluates the immunogenicity and antibody persistence of the BNT162b2 vaccine in people living with HIV (PLWH). Methods: We monitored anti-SARS-CoV-2 Spike IgG concentration in a cohort of PLWH at five time points (T0–T4) using chemiluminescent microparticle immunoassays (CMIAs) at the baselined both during and after vaccination. In severely immunocompromised individuals, a boosting dose was recommended, and participants and IgG concentration were measured in the two subgroups (boosted and not boosted). Results: In total, 165 PLWH were included, and 83% were male with a median age of 55 years (IQR: 47–62). At T1, 161 participants (97.6%) showed seroconversion with a median of IgG values of 468.8 AU/mL (IQR: 200.4–774.3 AU/mL). By T2, all subjects maintained a positive result, with the median anti-SARS-CoV-2 Spike IgG concentration increasing to 6191.6 AU/mL (IQR: 3666.7–10,800.8 AU/mL). At T3, all participants kept their antibody levels above the positivity threshold with a median of 1694.3 AU/mL (IQR: 926.3–2966.4 AU/mL). At T4, those without a booster dose exhibited a marked decrease to a median of 649.1 AU/mL (IQR: 425.5–1299.8 AU/mL), whereas those with a booster experienced a significant increase to a median of 13,105.2 AU/mL (IQR: 9187.5–18,552.1 AU/mL). The immune response was negatively influenced by the presence of dyslipidaemia at T1 (aOR 4.75, 95% CI: 1.39–16.20) and diabetes at T3 (aOR 7.11, 95% CI: 1.10–46.1), while the use of protease inhibitors (aORs 0.06, 95% CI: 0.01–0.91) and being female (aOR 0.02, 95% CI: 0.01–0.32) at T3 were protective factors. Conclusions: The immunogenicity of the BNT162b2 vaccine in PLWH has been confirmed, with booster doses necessary to maintain high levels of anti-SARS-CoV-2 Spike IgG antibodies, especially in patients with comorbidities. These findings underline the importance of a personalized vaccination strategy in this population.

Colostrum conductivity, pH and Brix index as predictors of passive immunity transfer in foals.

Foal immunity relies heavily on the absorption of colostrum immunoglobulins; thus, colostrum evaluation is used to predict the transfer of passive immunity (TPI), and its conductivity is associated with TPI in cattle. Leading up to and at parturition, a reduction in colostrum pH and conductivity is thought to be necessary for TPI; however, this remains to be determined. To assess conductivity, pH, and Brix refractometer index of colostrum to predict the TPI in foals. Field study. The colostrum of 241 mares was assessed for conductivity, pH, and Brix index using handheld devices immediately after parturition. Twenty-hour postpartum foals had complete blood cell count and plasma IgG concentrations assessed. Foals were split in complete versus incomplete TPI (i.e., IgG ≥8 g/L vs. <8 g/L). Mare (breed, duration of pregnancy, parity, and age), foal (sex), and colostrum (conductivity, pH, and Brix index) data were computed to assess factors affecting TPI. Multivariate regression and receiver operating characteristic (ROC) curves were employed for analysis. Complete TPI was achieved in 89.4% of foals. The ROC TPI values were conductivity ≤5 mS/cm (AUC = 0.68), Brix ≥23.4% (AUC = 0.70), and pH ≤6.4 units (AUC = 0.73). The odds ratio for TPI in 24 h post-partum was 6.1 (2.1-17.1, 95% CI) for conductivity, 3.2 (1.2-9.3, 95% CI) for pH, and 4.5 (1.5-12.7, 95% CI) for Brix index. Sensitivity and specificity of 93% (88-96 95% CI), 56% (44-7, 95% CI), 92% (87-96, 95% CI), 28% (14-47, 95% CI), 94% (88-97, 95% CI) and 18% (14-47, 95% CI) for conductivity, Brix and pH, respectively. Low incidence of incomplete TPI. Conductivity, pH and Brix are strong predictors of foals that succeed in the transfer of passive immunity; however, all three presented low to moderate specificity. The established cutoff values obtained herein can be used on-field by other foaling programs. All three handheld devices used in the study are inexpensive and ready to use on-farm.

Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts.

Systemic administration of nanomedicines results in the activation of the complement cascade, promoting phagocytic uptake and triggering proinflammatory responses. Identifying the biomarkers that can predict the "risk" of abnormally high complement responders can improve the safety and efficacy of nanomedicines. Polyethylene glycol (PEG) and dextran are two types of clinically approved polymer coatings that trigger complement activation. We performed a multifaceted analysis of the factors affecting the complement activation by PEGylated liposomal doxorubicin (PLD) and dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs) in plasma from patients with different inflammatory disease conditions and healthy donors. The complement activation (measured as deposition of the complement protein C3) varied greatly, with 29-fold and 26-fold differences for PLD and SPIO NWs, respectively. Chronic inflammation, acute infection, use of steroids, and sex had minor effects on the variable complement activation, whereas age inversely correlated with the complement activation. C-reactive protein level was not predictive of high (top 20th percentile) complement responses. Plasma concentrations of the main complement factors, as well as total IgG and IgM, showed no correlation with the activation by either nanoparticle. On the other hand, plasma concentrations of anti-PEG IgG and IgM showed a strong positive correlation with the activation by PLD. Particularly, titers of anti-PEG IgM showed the best predictive value for the "risk" of high complement activation by PLD. Titers of antidextran IgG and IgM showed a lower correlation with the activation by SPIO NWs and poor predictive value of the top 20% complement responses. Nanoparticle-bound immunoglobulins showed the best correlation with complement activation and a strong predictive value, supporting the critical role of immunoglobulins in inciting complement. The opsonization of PLD with C3 in plasma with high anti-PEG antibodies was predominantly via the alternative pathway. Characterizing the nature of nanoparticle-binding antibodies has important implications in mitigating and stratifying nanomedicine safety.

Features of immune status in patients with pulmonary tuberculosis after the COVID-19

BACKGROUND. Identification of immunological changes in patients with pulmonary tuberculosis after coronavirus infection will contribute to the prediction of its course and correction of therapeutic protocols. OBJECTIVE. The aim of the work is to determine the nature of immuno-mediated disorders caused by coronavirus disease (COVID-19) in patients with pulmonary sensitive tuberculosis (STB). MATERIALS AND METHODS. The results of a comprehensive immunological clinical and laboratory examination with subsequent computer processing of the data of 72 patients with STB of the lungs were analyzed. RESULTS. In the immune system of patients with pulmonary STB after COVID-19 the multidirectional changes are manifested by: a lower degree of increase of the blood leukocytes number (mainly due to a decrease in the absolute lymphocytes number), activation of the immune T-cells with an increase in the percent number and functional activity of pan-T-cells and T-helpers, an increase in the functional activity of T-suppressors, natural killers and killer T-cells (with the absolute and percent decrease of the latter), a higher level of the absolute and relative number of double positive (CD4+8+) cells and the functional activity of B-cells. A decrease in the level of IgA and an increase in the concentration of IgG with an decrease in the level of the medium and small circulating immune complexes, depression of the phagocytes link of immunity by reducing phagocyte number of phagocytes are observed in the blood of the patients with pulmonary STB after COVID-19. CONCLUSIONS. In the patients with pulmonary tuberculosis after COVID-19, the immune response is complex, with the crossing of immune reactions of pulmonary tuberculosis and post-COVID changes in immunity: on the one hand, previous COVID-19 promote compensatory activation of immune cells – T- and B-lymphocytes, natural killers; on the other hand, it causes suppression of antibacterial protection of mucous membranes (due to a decrease in the blood level of IgA) and reduces the body’s resistance (due to suppression of the phagocytes link of immunity).

Biochemical rationale for transfusion of high titre COVID-19 convalescent plasma

We aimed to model binding of donor antibodies to virus that infects COVID-19 patients following transfusion of convalescent plasma (CCP). An immunosorbent assay was developed to determine apparent affinity (Kd, app). Antibody binding to virus was modelled using antibody concentration and estimations of viral load. Assay and model were validated using reference antibodies and clinical data of monoclonal antibody therapy. A single Kd, app or two resolvable Kd, app were found for IgG in 11% or 89% of CCP donations, respectively. For IgA this was 50%-50%. Median IgG Kd, app was 0.8nM and 3.6nM for IgA, ranging from 0.1-14.7nM and 0.2-156.0nM respectively. The median concentration of IgG was 44.0nM (range 8.4-269.0nM) and significantly higher than IgA at 2.0nM (range 0.4-11.4nM). The model suggested that a double CCP transfusion (i.e. 500 mL) allows for > 80% binding of antibody to virus provided Kd, app was < 1nM and concentration > 150nM. In our cohort from the pre-vaccination era, 4% of donations fulfilled these criteria. Low and mid-range viral loads are found early post exposure, suggesting that convalescent plasma will be most effective then. This study provides a biochemical rationale for selecting high affinity and high antibody concentration CCP transfused early in the disease course.

Probiotic powder with polysaccharides from Wolfiporia cocos alleviates antibiotic-associated diarrhea by modulating immune activities and gut microbiota

To enhance immunomodulatory effects of lyophilized probiotics, we screened a new lyophilizing protective agent, that is Wolfiporia cocos polysaccharide (WP). This study demonstrated WP significantly increased the survival rate among seven polysaccharides, with the optimal dosage being 10 % (w/v). The ratio of bacterial suspension to lyophilizing protective agent was 1:2, in the condition, the probiotic survival rate of probiotics reached 83.06 %. Probiotic powder with WP (PWP) showed superior improvement in immune regulation and gut microbiota in antibiotic-associated diarrhea (AAD) mice compared to powder without WP. It notably increased IgM, IgG and IgA contents, and enhanced the activity of macrophage cells in the abdominal cavity. Furthermore, PWP exhibited the combined benefits of both the WP and PP in regulating the gut microbiota homeostasis, inhibiting the dysbiosis of the gut microbiota reflected in a significant increase in Proteobacteria, such as Sutterella, and decrease in Bacteroidetes, such as Muribaculaceae induced by AAD. Additionally, the correlation analysis indicated Sutterella had negative correlations with the immunomodulatory activities, meanwhile Muribaculace had positive correlations with the immunomodulatory activities. Overall, PWP could regulate the abundances of gut microbiota, thereby modulating immune activities and alleviating antibiotic-associated diarrhea, providing valuable insights for the development and application of WP in probiotics.

Evaluation of IgG and Complement Component C4 Levels in Low-Income Countries, Yemen Republic in Light of Their Proposed Role in the Hemolysis of Stored CPDA-1 Whole Blood.

Hemolysis is the most severe change that occurs in stored blood and can cause severe consequences in patients after transfusion. This study examines the potential role of IgG and complement, exampled by C4, in the hemolysis of stored CPDA-1 blood under poor storage conditions in low-income countries. The study was performed on 30 whole blood units (250 mL) drawn from convenience healthy volunteer donors with CPDA-1 anticoagulant and stored at 2-6 °C for 35 days. Each well-mixed blood bag was sampled at 0, 7, 21 and 35 days and examined for CBC, plasma hemoglobin, hemolysis percent and determination of IgG and C4. The plasma hemoglobin level and hemolysis percent increased continuously to reach 1.56 g/dl and 7.05% at the end of storage time. Hemolysis increased alongside the mean IgG concentration that was increased significantly from day 0 of storage (7.68±1.75 g/L) and peaked on day 7 (11.55±1.57 g/L), then declined to reach 8.33±2.09 g/L on day 35. Also, the mean concentration of C4 increased from day 0 of storage (0.15±0.06 g/L) to a peaked on day 21 (0.18±0.04) then declined on day 35 (0.17±0.06 g/L). The coordinated action of IgG and C4 is reflected by the positive correlation of their delta changes (r=0.616, p<0.0001). Elevated hemolysis percent in whole CPDA-1 stored blood in Yemen was accompanied by initial increase of IgG and C4 followed by final decline, which indicate their activation and consumption during hemolysis. Further studies for other hemolysis markers and analyses will give a full idea about that.

The effect of using Echinacea extract as an immune system stimulant and antioxidant on blood indicators, growth efficiency, and carcass characteristics in broiler chickens to produce a healthy product

This study aimed to discover how echinacea powder extract (EPE), an antioxidant, affects the growth rate, body composition, and blood parameters in broilers as an alternative to antibiotics. In a completely randomized design study, four experimental groups received 280 broiler chicks, 5 days old (Cobb 500). Each group was distributed into seven replicates, each containing ten unsexed chicks. Four groups were randomly selected from the chicks; the first group (the control group) was given drinking water only. Conversely, the birds in treatments 2, 3, and 4 were supplemented with EPA in their drinking water. They received 1.0, 2.0, and 3.0 cm3 EPA/liter water every 3 days weekly until the end of the trial (30 days). Our findings found significant differences in avian mass between experimental treatments during growth phases. The control group weighed 887 g, while the 3.0 cm3 EPE group weighed 850 g. The Duncan test showed a difference in FI and FCR among those favoring the EPE groups. Our results showed no significant changes in carcass features, except for spleen, gizzard, and abdominal fat, with the 3.0 cm3 EPE group having weight-higher organs and lower abdominal fat. Also, the control had higher TP, albumin, and globulin levels, while the EPE diet increased ALT and AST and decreased TC, TG, LDL, and VLDL levels. Furthermore, EPE-containing diets resulted in higher IgG concentrations, lower MDA levels, and higher SOD activity compared to the control group. According to the ANOVA analysis, the water consumption rate did not significantly differ across the trial groups. It included adding EPE with 3.0 cm3 enhanced growth performance, carcass traits, and antioxidant activity to obtain health outcomes for end users.

Monitoring humoral responses against three SARS-CoV-2 vaccines in a university population from Chihuahua, Mexico.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread worldwide since 2019. Survey of the antibodies against SARS-CoV-2 is one of the most important measures of immunity since it can give an idea on the effectiveness of administered vaccines and the serologic status of individuals. We determined the concentrations of blood IgM and IgG against three SARS-CoV-2 proteins in vaccinated teachers and students among a university population from Chihuahua, Mexico. Humoral response surveillance against the 3C-like proteinase (3CLpro), nuclear protein (NP), and receptor binding domain (RBD) of SARS-CoV-2 was carried out. A total of 239 samples were analyzed: 67 from teachers who were vaccinated with CanSino and 172 from students (27.9% were vaccinated with AstraZeneca, 32.6% with Sinovac, 24.4% with Pfizer-BioNTech, 15.1% with other vaccines). Significant differences in the levels of IgG were observed between serum from individuals prior to vaccination (preimmunization serum) and from those that were vaccinated with CanSino. However, samples from asymptomatic individuals did not show differences between the preimmunization and post-immunization serum. The three vaccinated groups (AstraZeneca, Pfizer and Sinovac) did not show significant differences in anti-RBD IgG antibody titers compared to the positive control group, except for a Pfizer non-COVID-19 subgroup where the level of antibodies in the Pfizer group was 1.7 times higher. Neither vaccine group showed significant differences between those individuals who previously had COVID-19 and uninfected individuals. These results provide a picture of the situation at the time when in-person classes resumed.

Fractional Doses of Pneumococcal Conjugate Vaccine - A Noninferiority Trial.

Pneumococcal conjugate vaccines are an expensive component of the routine immunization schedule. Fractional-dose regimens may be one option to increase the sustainability of the vaccine program. We assessed whether the immunogenicity of fractional doses of the 10-valentand 13-valent pneumococcal conjugate vaccines (PCV10 [GSK] and PCV13 [Pfizer], respectively) would be noninferior to that of the full doses and analyzed the prevalence of vaccine-serotype carriage. We randomly assigned healthy infants in Kenya to one of seven equal-sized trial groups. Participants in groups A through F were assigned to receive either a fractional or full dose of PCV10 or PCV13, administered as two primary doses plus one booster dose. In group A, participants received a full dose of PCV13; group B, a 40% dose of PCV13; group C, a 20% dose of PCV13; group D, a full dose of PCV10; group E, a 40% dose of PCV10; and group F, a 20% dose of PCV10. Participants in the seventh group (group G) received a full dose of PCV10 as three primary doses without a booster. Immunogenicity was assessed 4 weeks after the primary series of doses and 4 weeks after the booster dose. Noninferiority could be declared 4 weeks after the primary series if the difference in the percentage of participants with a threshold response was not more than 10% and 4 weeks after administration of the booster if the ratio of the geometric mean concentration (GMC) of IgG was more than 0.5. A vaccine dose was prespecified as noninferior if it met the noninferiority criterion for at least 8 of the 10 vaccine types in the PCV10 groups or at least 10 of the 13 vaccine types in the PCV13 groups. Carriage was assessed when participants were 9 months and 18 months of age. In the per-protocol analysis, 40% of a full dose of PCV13 met the noninferiority criterion for 12 of 13 serotypes after the primary series and for 13 of 13 serotypes after the booster. The immunogenicity of the 20% dose of PCV13 and of the 40% and 20% doses of PCV10 was not noninferior to that of the full doses. Vaccine serotype-type carriage prevalence was similar across the PCV13 groups at 9 months and 18 months of age. In a three-dose schedule (two primary doses and a booster), 40% doses of PCV13 were noninferior to full doses for all included serotypes. Lower doses of PCV13 and PCV10 did not meet the criteria for noninferiority. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03489018; Pan African Clinical Trial Registry number, PACTR202104717648755.).

Analiza różnic w stężeniu przeciwciał przeciw SARS-CoV-2 w przebiegu COVID-19 w zależności od ciężkości choroby, płci, wieku i statusu szczepienia

Introduction and objectiveThe role of immunoglobulin G antibodies in combating SARS-CoV-2 infection, modulation of COVID-19 disease severity, and persistence of humoral response after primary infection and vaccination is unclear. This study aimed to evaluate the role of antibodies in limiting the infection, modulating disease severity, and determining the durability of the immune response depending on the clinical status of patients, their age, sex, and vaccination status.Material and methodsThe study involved 156 patients, 99 men and 57 women, aged 58.3 ± 12.5 years old, hospitalised for pneumonia in the course of COVID-19, with infection confirmed by real-time polymerase chain reaction test. The concentration of anti-SARS-CoV-2 IgG antibodies was tested at 3, 6, and 9 months from the day of hospitalisation.ResultsThe concentration of anti-SARS-CoV-2 IgG antibodies in patients with severe COVID-19 was higher compared to the group of patients with mild to moderate disease. The level of anti-SARS-CoV-2 IgG antibodies was comparable in men and women. In patients over 60 years of age, a lower concentration of antibodies was observed than in patients under 60 years of age. In the vaccinated group, the level of antibodies was higher than in the unvaccinated group.ConclusionsThe study findings showed that the concentration of IgG anti-SARS-CoV-2 antibodies was not a parameter dependent on the sex of the patients, but rather on the severity of the disease and the age of the patients and their vaccination status.