Antibody Levels Research Articles

Clinical significance of serum Helicobacter pylori antibody cytotoxin-associated gene A levels in patients with unstable angina

ObjectivesWe investigated the clinical significance of serum Helicobacter pylori cytotoxin-associated gene A (CagA) antibody levels in 768 patients with unstable angina (UA).MethodsSerum CagA levels were measured using ELISA. Demographic data, serum biomarkers, and SYNTAX scores were collected. Patients were followed up for 1 year for major adverse cardiac events (MACE).ResultsCagA-positive UA patients had higher total cholesterol and hsCRP levels, and SYNTAX scores. CagA levels correlated positively with TC, hsCRP, and SYNTAX scores. Kaplan–Meier analysis showed shorter MACE-free survival in CagA-positive UA patients. CagA levels predicted MACE occurrence within 1 year, along with SYNTAX scores.ConclusionsSerum H. pylori CagA antibody positivity is associated with worse prognosis in UA patients. CagA levels correlate with lipid metabolism and inflammatory markers.

Identification and Allergenicity Analysis of Tropomyosin: A Heat-Stable Allergen in Lateolabrax japonicus.

Lateolabrax japonicus, a prevalent aquatic delicacy, is known to elicit allergic reactions in certain individuals. Nevertheless, the investigation into its allergenic components has remained notably inadequate. In the research, an approximately 35 kDa heat-stable protein of L. japonicus raw/steamed extracts was verified as tropomyosin (TM) by LC-MS/MS. Open reading frame of TM (852 bp) was acquired via PCR amplification, encoding 284 amino acids. The IgE-binding frequency of TM expressed in Escherichia coli was 22.5% among 80 fish-sensitized patients. Furthermore, TM had the ability to activate basophils in 7 patients. In the Balb/c mice model, compared with the PBS group, the levels of specific antibodies (IgE, IgG1, and IgG2a), CD19+ B cells, IL-4, and IL-10 were significantly increased in the TM group. However, the opposite was indeed the case for CD4+ TCR-β, CD4+ CD25+ Fox p 3+ cells, and IFN-γ. These findings regarding an allergen assist in conducting component-resolved diagnoses and therapeutic research for fish allergy.

Incidence and risk factors of hepatitis E virus infection in women with gynecological tumors in Eastern China

Background Recently, there has been increasing interest in the exploration of the association between the hepatitis E virus (HEV) infection and malignancies; however, epidemiological data for HEV infection among women with a gynecological tumors (GT) are limited. Herein, we investigated the correlation between HEV and GT in Chinese women. Methods We recruited 452 women diagnosed with a primary GT and 452 healthy volunteers to investigate the possible routes and risk factors for HEV infection. The serum antibody levels of anti-HEV IgG and IgM were measured by enzyme-linked immunoassays once a year. Results After a median follow-up time of 5.4 years (range 4 to 7 years), the overall detection rate of anti-HEV antibodies in patients with GT and in controls were 69/452 (15.27%) and 23/452 (5.09%) (P = 0.001), respectively. The seroprevalence of anti-HEV IgG antibodies was significant higher in patients with GT (15.27%) than in healthy controls (5.09%) (P = 0.001). Moreover, 13 (2.88%) patients with GT were positive for IgM antibodies, while only 4 (0.88%) healthy controls tested positive for anti-HEV IgM antibodies (P = 0.028). The highest prevalence of HEV antibodies were detected in patients with ovarian borderline tumors (40%), followed by patients with ovarian cancer (20.54%) and endometrial cancer (18.46%). Multivariable analysis revealed that contact with dogs (OR, 1.88; 95% CI [1.10–3.22]; P = 0.015) and a history of anti-tumor chemotherapy (OR, 1.85; 95% CI [1.07–3.20]; P = 0.028) were independent risk factors for HEV infection. Conclusion Overall, the present study showed that patients with GT are more susceptible to HEV infection in Eastern China, particularly in patients with ovarian borderline tumors. Thus, effective strategies are needed to reduce HEV infection in patients with GT.

Fucoidan-Mediated Covalent Modification Mitigates Allergenicity of Shrimp (Penaeus vannamei) in Mice via Enhanced Intestinal Barrier Function and Antigen Presentation Suppression.

Covalent modification is an effective strategy for reducing the allergenicity of single allergens. However, due to the complexity of the food matrix, its application in hypoallergenic food production requires further exploration. The study showed that covalent modification of fucoidan decreased the specific antibody levels, inhibited Th2 cell differentiation, and reduced mast cell degranulation, suggesting that it significantly reduced the allergenicity of Penaeus vannamei. Further analysis showed that covalent modification not only up-regulated the intestinal tight junction proteins expression and improved intestinal mucus secretion but also restored intestinal microbial homeostasis by immunological and 16S rRNA gene sequencing. Additionally, covalent modification inhibited dendritic cell maturation and CD8+ T cell differentiation, thereby reducing antigen recognition and presentation, as determined by transcriptome and flow cytometry. Therefore, the covalent modification of fucoidan reduced shrimp allergenicity by enhancing intestinal barrier function and inhibiting antigen presentation. In conclusion, it is a potential strategy for processing hypoallergenic foods.

Comparing the protection of heterologous booster of inhaled Ad5-nCoV vaccine and hybrid immunity against Omicron BA.5 infection: a cohort study of hospital staff in China

BackgroundAfter the exit “zero-COVID” strategy in mainland China by the end of 2022, a large-scale COVID-19 outbreak seeded by Omicron variants occurred. An inhaled adenovirus type-5 vector-based (i.e., inhaled Ad5-nCoV) COVID-19 vaccine was licensed earlier in 2021. In this study, we aimed to assess the real-world effectiveness of a heterologous booster of inhaled Ad5-nCoV vaccine against Omicron infection and compared with the protection from hybrid immunity (i.e., prior breakthrough infection).MethodsIn this retrospective cohort study, we identified 1087 out of a total of 1146 hospital staff from a tertiary hospital in Urumqi city, China from November 22 to December 29, 2022. Demographic characteristics, baseline health status, occupation, behavioral factors, laboratory test of serological IgG antibody, and timeline from immunization to laboratory-testing outcome were obtained. We analysed the individual-level vaccination status of inhaled Ad5-nCoV vaccine, prior SARS-CoV-2 infection status and baseline vaccination status, and other risk factors before follow-up. The protective effects of the heterologous inhaled Ad5-nCoV vaccine and hybrid immunity against Omicron BA.5 infection and hospitalization were calculated as relative rate reduction (RRR), which was estimated using multivariate Poisson regression models.ResultsA total of 1087 hospital staff (median age of 34 years, and 343 males [31.6%]), including 931 accepted for serological antibody tests, were recruited to assess the vaccine effectiveness (VE) of the inhaled Ad5-nCoV booster and hybrid immunity. Among the 1087 participants, 413 had a history of prior SARS-CoV-2 infection (before follow-up) but did not receive an inhaled Ad5-nCoV booster, and 674 reported no prior infection, including 390 who received an inhaled Ad5-nCoV booster. The highest serological IgG antibody level was detected among the inhaled Ad5-nCoV group, with a median of 294.59 S/CO, followed by the hybrid immunity group, with a median of 93.65 S/CO compared to the reference level of the inactivated vaccine group (most of whom received the Sinopharm/BBIBP-CorV vaccine). The inhaled Ad5-nCoV booster and hybrid immunity yielded RRRs of 41.9% (95% CI: 24.8, 55.0) and 97.9% (95% CI: 94.2, 99.2), respectively, against Omicron BA.5 infection, regardless of symptom status.ConclusionWe found that hybrid immunity could provide a high level of protection against Omicron infection, while a heterologous inhaled Ad5-nCoV booster conferred a moderate level of protection. Our findings supported the rollout of a heterologous vaccination strategy regardless of preexisting vaccine coverage.

PM2.5-induced oxidative stress upregulates PLA2R expression in the lung and is involved in the pathogenesis of membranous nephropathy through extracellular vesicles

BackgroundParticulate matter (PM2.5) has been implicated in the development of membranous nephropathy (MN), but the underlying mechanism has yet to be fully understood. Oxidative stress is an essential factor of PM2.5-related toxicity and plays a significant role in the exposure of target antigenic epitopes in MN. This study aims to explore the pathogenic effects of PM2.5 in facilitating the crosstalk between the lung and kidney in MN.MethodWe examined oxidative stress indicators and the circulating levels of extracellular vesicles (EVs) in patients diagnosed with MN. Additionally, we assessed the expression of M-type phospholipase A2 receptor (PLA2R) in human lung tissue ex vivo. To verify the impact of PM2.5 on PLA2R expression in the lung and the kidney, we stimulated human bronchial epithelial cells (Beas-2B) with lipopolysaccharide (LPS) or PM2.5. We then treated podocytes in vitro with the supernatants from PM2.5-exposed Beas-2B cells, intervening with GW4869, an inhibitor of EV release, to explore the role of EV-mediated cell-cell interactions.ResultsWe found that elevated serum markers of oxidative stress and increased levels of PLA2R + EVs correlated positively with anti-PLA2R antibody levels in the serum of patients with idiopathic MN (IMN). Notably, PLA2R expression was significantly higher in the lung tissue of smokers, suggesting a possible link between PLA2R and oxidative stress. In vitro experiments demonstrated that PLA2R expression in Beas-2B cells was upregulated upon stimulation with LPS and PM2.5, an effect that could be reversed by the antioxidant glutathione (GSH). Furthermore, the supernatants from PM2.5-exposed Beas-2B cells were found to induce PLA2R overexpression and injury in podocytes, with this effect being mitigated by GW4869, an inhibitor of EVs release.ConclusionOur study contributes new knowledge to the understanding of how environmental pollutants, such as PM2.5, cause kidney damage through oxidative stress and EV-mediated signaling. The findings pave the way for further research into therapeutic strategies targeting oxidative stress and EVs, which could potentially improve patient outcomes of MN, particularly in high-risk populations like smokers and those exposed to air pollution.

Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection

IntroductionUpon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.MethodIn this study, convalescent individuals with stable RBD antibody levels (n=14, “sustainers”) were compared with donors (n=13) with the greatest antibody decline from a cohort of 132. To investigate the role of the cellular immune compartment in the maintenance of antibody levels, SARS-CoV-2-specific responses at 4 to 6 weeks post-mild COVID-19 infection were characterized using deep immune profiling.ResultsBoth groups had similar frequencies of total SARS-CoV-2-specific B and CD4+ T cells. Sustainers had fewer Spike-specific IgG+ memory B cells early after infection and increased neutralizing capacity of RBD antibodies over time, unlike the declining group. However, declining IgG titers correlated with lower frequency of Spike-specific CD4+ T cells.ConclusionThese data suggest that “sustainers” have unique dynamics of GC reactions, yield different outputs of terminally differentiating cells, and improve the quality of protective antibodies over time. This study helps identify factors controlling formation of long-lived PC and sustained antibody responses.

Experimental Induction of Anti-Muscarinic Type-3-Receptor Extracellular Loop Antibodies by Immunization with 4-Hydroxy-2-nonenal Modified Ro60 and Unmodified Ro60.

Sjögren's Disease (SjD) subjects have decreased lacrimal/salivary gland function. Studies have proposed that autoantibodies targeting G-protein-coupled muscarinic acetylcholine-type-3-receptor (M3R) are potential clinical markers for SjD. We hypothesized that rabbits/mice immunized with 4-hydroxy-2-nonenal (HNE)-modified/unmodified Ro60 will develop an autoimmunity, specifically a SjD phenotype, thus expressing increased levels of anti-M3R antibodies. We immunized two rabbits each with 10mM HNE-modified Ro60/unmodified Ro60 antigen or Ro274-290/Ro413-428/Ro500-517 Ro60 peptides. Two rabbits each were immunized with either M3R second extracellular loop (ECL2) or M3R ECL3 peptide. Finally, five groups of BALB/c mice were immunized as follows-Group-I immunized with Ro60, Groups-II-IV immunized with Ro60 modified with 0.4mM (low), 2mM (medium) and 10mM (high) HNE respectively and Group-V-Freund's adjuvant. Serum antibodies to M3R ECL2/ECL3/Ro60/La or Sm were detected by ELISA. Functional assays were also performed. Immunization with HNE-modified Ro60/unmodified Ro60 antigen or Ro274/Ro 413/Ro500 peptides induced a rapid intermolecular epitope spreading to M3R ECL2/ECL3, especially to M3R ECL3 in HNE-Ro immunized rabbits. These animals did not bind to scrambled M3R peptides. Ro60-immunized rabbit IgG inhibited M3R activity in a functional assay. Rabbits immunized with ECL2/ECL3 developed high reactivity to Ro60 but not against Sm/RNP. We found a differential antibody-induction against M3R ECL2 with Group-3 mice developing significant reactivity. Our data show induction of increasing anti-M3R antibodies in rabbits immunized with Ro60/HNE-Ro60 or Ro60 peptides and differential induction of these antibodies in mice immunized with Ro60 modified with increasing HNE. These findings suggest that M3R ECL2/ECL3 are involved in SjD autoimmunity progression.

Evaluation of thyroid function tests among children with neurological disorders

BackgroundThyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy.MethodsOur study employed a combination of meta-analysis and case-control design. For the meta-analysis, we conducted a systematic search of online databases for studies that compared thyroid function tests in children with neurological disorders to controls. In our case-control study, we recruited a total of 11836 children, comprising 7035 cases and 4801 healthy controls. Wilcoxon Rank Sum Test was used to determine characteristics of thyroid function between the cases and healthy controls. In order to exclude the false discovery rate (FDR), the Benjamini-Hochberg (BH) procedure is applied.ResultsA total of 12 relevant literature sources were included in the meta-analysis. Compared with controls, free thyroxine (FT4) levels were significantly decreased in neurological disorders in meta-analysis (MD = -0.29, 95% CI: -0.50 to -0.09), whereas thyroid-stimulating hormone (TSH) levels showed no significant difference (MD = -0.07, 95% CI: -0.36 to 0.21). In our case-control study, levels of free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and anti-thyroglobulin antibodies (TG-Ab) were notably reduced among individuals with neurological disorders, compared with healthy controls (P<0.001, P<0.001, P=0.036, P=0.006). However, thyroid-stimulating hormone (TSH) levels did not show any statistically significant differences among the cases and controls.ConclusionsOur research demonstrates that, in comparison to controls, children with neurological disorders exhibited a significant decrease in FT4 levels, while TSH levels remained unchanged. This finding provides a reference for potential serum marker of neurological disorders in children. Replication in future studies with the assessment of THs is needed to determine whether thyroid function should be included as a routine screening in these children.

Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study.

The GENCOV study sought to evaluate serological differences between individuals with differing COVID-19 severity and outcomes. We assessed the SARS-CoV-2 antibody response of GENCOV participants cross-sectionally 1-, 6-, and 12-months following COVID-19 diagnosis to identify patient factors associated with more robust and durable humoral immune responses. COVID-19 patients and a control cohort of vaccinated infection-naïve participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Commercially available and laboratory-developed serological assays were used to characterize features of participants' antibody responses, including both binding and neutralizing antibodies. Regression analyses were performed to identify associations between participant characteristics and features of the SARS-CoV-2 antibody response. Samples were obtained from participants 1- (n = 938), 6- (n = 842), and 12-months (n = 662) post-infection or vaccination. At all time points, vaccinees, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody levels compared to unvaccinated participants. Increasing age and/or illness severity were associated with significantly higher antibody levels among unvaccinated participants. Among vaccines, those who were vaccinated after infection (i.e., hybrid immunity) had consistently higher antibody levels compared to participants who were infection-naïve or vaccinated before their infection (i.e., breakthrough infections). Additionally, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody levels across all time points. Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.

Correlation between Insulin antibodyand HbA1c in Diabetes Mellitus

Insulin antibodies (INAs) are found in both types of diabetic patients and have low binding capacity and high affinity leading to hypoglycemia or hyperglycemia in type II patients taking insulin, which differs from the insulin antibodies found in type I that contain a high capacity of insulin binding and low affinity. This work aims to detect the levels of insulin antibodies and HbA1c in diabetic patients, and find the correlation between them and its potential role in glucose control. The study involved 60 patients with diabetes, divided into two groups type I and type II, each group containing 30 patients, in addition to 30 healthy individuals as a control group. High-performance liquid chromatography in a D-10 analyzer was used to measure HbA1c while ELISA was used to measure INAs in control and patients .Results: The current finding showed significant an elevated mean levels of HbA1c and INAs in both of patients groups compare to healthy, and there was non-significant weak positive correlation between them (R= 0.107 , P= 0.4 ).Together, elevated levels of HbA1c and INA, and the positive correlation between their levels, provide evidence of the effect of insulin antibodies on glycemic control and the effects of HbA1c levels in patients with diabetes.

Characterisation of specific responses to three models of viral antigens in immunocompetent older adults

BackgroundMemory responses to the antigens that an individual encounters throughout life may vary with the intensity and duration of antigen contacts or even with changes in immune status over time. This work aims to characterise specific responses to latent CMV, seasonal influenza and novel SARS-CoV-2 infections in immunocompetent individuals over 60 years of age. Specific cellular and humoral responses were identified by IFN-γ and granzyme B release by ELISpot and antibody level measurement. T lymphocyte subpopulation phenotypes were characterised by flow cytometry.ResultsCellular and humoral responses to these viruses were detected in almost all patients. Influenza and SARS-CoV-2 cellular responses were positively correlated. There was no significant correlation between CMV and influenza or SARS-CoV-2 responses although both were consistently lower in CMV-seropositive patients. CMV responses were negatively correlated with the levels of the least differentiated subsets of T lymphocytes, and positively correlated with the most differentiated ones, contrary to what happened with the influenza responses. Nevertheless, SARS-CoV-2 cellular responses were negatively correlated with the most differentiated CD8+ T lymphocytes, while humoral responses were negatively correlated with the least differentiated T lymphocytes. Responses to the three viruses were correlated with a Th1/Th2/Th17 balance in favour of Th1.ConclusionsThe results indicate that memory responses differ depending on the durability of the antigen stimulus. Cellular responses to novel pathogens resemble those generated by seasonal but not CMV infection. Subpopulation distribution and the level of specific T lymphocytes against previous pathogens could be used as immunocompetent status biomarkers in older adults reflecting their ability to generate memory responses to new pathogens.

SARS-CoV-2 antibodies in breast milk of women given one and two doses of COVID-19 vaccine

Background & objectives The COVID-19 pandemic underscores the significance of vaccination in mitigating disease spread, with Covishield and Covaxin serving as pivotal vaccines in India. Breast milk, rich in vital antibodies like IgA and IgG, plays a crucial role in enhancing the immune defence of breastfeeding infants. However, limited research exists on the antibody responses in breast milk among individuals receiving single versus double doses of the COVID-19 vaccine. This study aimed to bridge this gap by exploring IgA and IgG antibody levels in breast milk and assessing the correlation with COVID-19 vaccination status. Methods This hospital-based descriptive study aimed to assess the relationship between COVID-19 vaccination and the presence of anti-SARS-CoV-2 IgA/IgG antibodies in breast milk. Breast milk samples were collected using a sterile, closed-system electric breast pump and stored at -20°C. ELISA testing, utilizing commercially available kits, was utilized to assess anti-SARS-CoV-2 IgA and IgG antibodies. Results Among the 151 women participants, 76 (50.3%) received COVID-19 vaccination. Of these vaccinated women, 70 (92.1%) received Covishield, and 6 (7.9%) received Covaxin. Within the vaccinated cohort, 32 (42.1%) completed the recommended double-dose regimen, while 44 (57.9%) received a single dose. While no significant association was found between vaccination status and IgA positivity (P=0.491), a notable association emerged for IgG positivity (P<0.001). Notably, individuals who completed the recommended double-dose regimen exhibited higher IgA (63.6%) and IgG (65.4%) positivity compared to those receiving a single dose. Interpretation & conclusions This study underscores the significance of COVID-19 vaccination in impacting IgA and IgG antibody presence in breast milk. Completing the double-dose regimen correlated with higher IgA and IgG levels, emphasizing the benefits of complete vaccination. These findings contribute to understanding vaccination’s impact on maternal-infant health.

Association Between Quantitative Sialoscintigraphy and Antibody Profiles in Patients With Sjögren or Sicca Syndrome.

This study analyzed the association between anti-Ro/SSA and anti-La/SSB antibody levels with quantitative and visual sialoscintigraphy patterns in patients suspected of having Sjögren or sicca syndrome. Medical records of patients who underwent sialoscintigraphy between April 2020 and May 2022 were reviewed. Associations between antibody levels and sialoscintigraphy parameters were evaluated using linear regression. Receiver operating characteristic curve analysis was used to identify antibody cutoff values for predicting flat-type patterns and the risk of Sjögren or sicca syndrome. Of the 170 patients (mean age, 56.6 years; 78.8% female), 95.3% had dry mouth and eyes, 30% experienced polyarthralgia, and 66.5% were prescribed hydroxychloroquine. The most common sialoscintigraphy finding was the median-type time-activity curve (TAC) pattern. Anti-Ro/SSA and anti-La/SSB levels were significantly correlated with maximum accumulation or maximum secretion in the salivary glands. Receiver operating characteristic analysis for anti-Ro/SSA predicting a flat-type TAC pattern showed an area under the curve (AUC) of 0.659 to 0.780, with specificity between 82.1% and 86.3% for antibody levels greater than 85.2 units. Anti-Ro/SSA levels greater than 49.75 units predicted a higher risk of Sjögren or sicca syndrome, with an AUC of 0.622 and 83.9% specificity. Anti-La/SSB levels had no significant predictive value, with an AUC of 0.554. Anti-Ro/SSA levels greater than 85.2 units were strong predictors of flat-type TAC patterns, indicating near-total salivary gland dysfunction and supporting their diagnostic utility in Sjögren or sicca syndrome.

Evaluation of the immune status of dogs vaccinated against rabies by an enzyme-linked immunosorbent assay using crude preparations of insect cells infected with a recombinant baculovirus encoding the rabies virus glycoprotein gene.

Evaluation of the effectiveness of vaccination of animals against rabies is not routinely implemented. In cases where it is carried out, the rapid fluorescent focus inhibition test (RFFIT) or the fluorescent antibody virus neutralization (FAVN) test are the recommended tests. However, both of these tests require handling of live rabies virus (RABV), and are cumbersome to perform. In view of this, the enzyme-linked immunosorbent assay (ELISA) has been proposed as a surrogate test; however, availability of appropriate antigen is a major impediment for the development of ELISAs to detect anti-rabies antibodies. The most widely used antigen is the RABV glycoprotein (G) purified from cell culture-propagated virus, which requires a biosafety level 3 containment. The alternative is to use recombinantly expressed G, which needs to be to be properly glycosylated and folded to serve as the best antigen. The most suitable system for its production is the baculovirus expression system (BVES). However, purification of RABV G is challenging. We therefore tested partially purified preparations in the form of extracts of insect cells infected with baculovirus expressing RABV G, against sera from vaccinated dogs in an indirect ELISA. The results showed good concordance against RFFIT, with sensitivity and specificity of 90.48% and 80.00%, respectively. The system may be used for quick screening to determine the presence and an approximate level of antibodies, and can be modified to enable monitoring of mass dog vaccination programs, as well as to facilitate certification of dogs intended for international travel and transportation.

Peripheral Neuropathy in the Phase 3 ASPEN Study of Bruton Tyrosine Kinase Inhibitors for Waldenström Macroglobulinemia.

Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN. Logistic regression was performed between PN symptom resolution and several predictors. Health-related quality of life (HRQOL) was assessed using the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Forty-nine patients with PN symptoms were included (zanubrutinib treated, n=27; ibrutinib treated, n=22). Overall, 35 patients (71.4%) experienced resolution of PN symptoms, with a median time to resolution of 10.1 months (range, 1-46.8). In cohort 1 (MYD88 mutation), the median time to PN symptom resolution was 4.6 months (range, 1.1-46.8) with zanubrutinib and 14.1 months (range, 1-44) with ibrutinib. Logistic regression demonstrated a significant relationship between PN symptom resolution and both major response (hazard ratio [HR], 10.67 [95% CI,2.20-51.81]; P=.0033) and lower baseline anti-MAG antibody levels (HR, 0.72 [95% CI, 0.52-1.00]; P=.0486). Patients with PN symptom resolution had greater improvement in HRQOL. Physical functioning improved in patients with PN symptom resolution and was unchanged in patients without resolution. Improvements observed in PN symptoms may be in response to a reduction in IgM. While further investigation is required, this analysis supports the potential use and further exploration of Bruton tyrosine kinase inhibitors to treat PN symptoms in patients with WM. ClinicalTrials.gov: NCT03053440.

Kinetics of naturally induced binding and neutralising anti-SARS-CoV-2 antibody levels and potencies among SARS-CoV-2 infected Kenyans with diverse grades of COVID-19 severity: an observational study.

Given the low levels of coronavirus disease 2019 (COVID-19) vaccine coverage in sub-Saharan Africa (sSA), despite high levels of natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of naturally acquired immunity. We measured whole-spike immunoglobulin G (IgG) and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody-neutralising potency against the wild-type (Wuhan) SARS-CoV-2 pseudovirus in a subset of 51 patients over three successive time points. Binding and neutralising antibody levels and potencies were then tested for correlations with COVID-19 severities. Rates of seroconversion increased from day 0 (day of PCR testing) to day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike-IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at day 28 (p<0.01) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody-neutralising potencies peaked at day 28 (p<0.01) but declined by three-fold, six months after COVID-19 diagnosis (p<0.01). Binding antibody levels were highly correlated with neutralising antibody potencies at all the time points analysed (r>0.60, p<0.01). Levels and potencies of binding and neutralising antibodies increased with disease severity. Most COVID-19 patients generated SARS-CoV-2 specific binding antibodies that remained stable in the first six months of infection. However, the respective neutralising antibodies decayed three-fold by month-six of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere in the world. Thus, regular vaccination boosters are required to sustain the high levels of anti-SARS-CoV-2 naturally acquired neutralising antibody potencies in our population.

Antibody Avidity Maturation Following Booster Vaccination with an Intranasal Adenovirus Salnavac Vaccine

Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of these antibodies. The avidity of serum antibodies is associated with a vaccine showing high effectiveness and reflects the process of affinity maturation. In the context of vaccines against SARS-CoV-2, only a limited number of studies have investigated the avidity of antibodies, often solely focusing on the wild-type virus following vaccination. This study provides new insights into the avidity of serum antibodies following adenovirus-based boosters. We focused on the effects of an intranasal Salnavac booster, which is compared, using a single analytical platform, to an intramuscular Sputnik V. Methods: The avidity of RBD-specific IgGs and IgAs was investigated through ELISA using urea and biolayer interferometry. Results: The results demonstrated the similar avidities of serum antibodies, which were induced by both vaccines for six months post-booster. However, an increase in antibody avidity was observed for the wild-type and Delta variants, but not for the BA.4/5 variant. Conclusions: Collectively, our data provide the insights into antibody avidity maturation after the adenovirus-based vaccines against SARS-CoV-2.

Enhanced levels of IL-6 and PAI-1 and decreased levels of MMP-3 in cytomegalovirus seropositive patients with prior myocardial infarction

BackgroundEfforts to understand atherosclerosis, a major cause of ischemic heart disease, have linked several lifestyle factors to increased risk for developing cardiovascular disease. Some studies suggest that cytomegalovirus (CMV), a widely prevalent herpesvirus, is reactivated in atherosclerotic plaques and associated with higher cardiovascular mortality risk. We aimed to explore whether CMV seropositivity and CMV-IgG antibody levels correlate with relevant biomarkers in a cohort of patients with myocardial infarction (MI) and matched controls. Methods and resultsWe analyzed a dataset from 324 survivors of MI treated in Stockholm between 1996 and 2001. Blood samples collected three months after MI were used to measure protective Apo B100 autoantibodies, metabolic, and inflammatory biomarkers. CMV serology was performed on stored serum samples. Correlation analyses were conducted between biomarkers and CMV serostatus in 324 patients and age- and sex-matched controls. While CMV seroprevalence was equal, the CMV-IgG levels were higher in controls. Among various factors examined, CMV seropositive MI patients had elevated levels of plasminogen activator inhibitor-1 (PAI-1) and interleukin-6, along with lower levels of MMP-3, than CMV seronegative MI patients. CMV-IgG levels correlated positively with PAI-1 levels in patients. Although CMV seropositivity was associated with increased proinsulin levels, there was no correlation with diabetes diagnosis. ConclusionsOur findings suggest an enhanced inflammatory and prothrombotic state in CMV seropositive patients after MI. Notably, patients had lower levels of CMV IgG than controls.

Assessment of Thyroid Function Status and Thyroid Antibody Levels Among Tribal Population of Jarugumalai Hills of Salem District, Tamil Nadu, India

Background: Tribal population not only suffers from malnutrition and communicable diseases but also from non-communicable diseases. Globally, one of the most frequent metabolic disorders include thyroid disorders. The study was conducted to estimate the prevalence of Thyroid disorders using Thyroid Function Test, to determine the Anti-Thyroid Peroxidase Antibody levels among the tribal population, and also to determine the factors associated with thyroid disorders among the tribal population. Materials and Methods: It is a community based analytical cross-sectional study conducted among 375 tribal residents of Jarugumalai hills. Data was collected using a pre tested semi-structured questionnaire. Categorical variables were described using frequency and percentage. Variables significantly associated with thyroid disorders were identified using univariate and multivariate analysis. Results: Nearly 32% had any form of thyroid disorders. About 18% and 7% respectively had subclinical hypothyroidism and overt hypothyroidism. Also, 12% of the study participant blood samples were positive for Anti Thyroid Peroxidase antibody (ATPO). Female gender Usage of inadequately iodised salt and presence of ATPO were significantly associated with thyroid disorder on multivariate analysis. Conclusion: Thyroid status assessment showed a high prevalence (32%) among the marginalized population. Multi-pronged approach involving educational, administrative and legal measures must be implemented to curb this problem.