Serum Immunoglobulin G Research Articles

AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection

The nasal mucosa is an important initial site of host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, intramuscularly administered vaccines typically do not achieve high antibody titers in the nasal mucosa. We measure anti-SARS-CoV-2 spike immunoglobulin G (IgG) and IgA in nasal epithelial lining fluid (NELF) following intramuscular vaccination of 3,058 participants from the immunogenicity substudy of a phase 3, double-blind, placebo-controlled study of AZD1222 vaccination (ClinicalTrials.gov: NCT04516746). IgG is detected in NELF collected 14days following the first AZD1222 vaccination. IgG levels increase with a second vaccination and exceed pre-existing levels in baseline-SARS-CoV-2-seropositive participants. Nasal IgG responses are durable and display strong correlations with serum IgG, suggesting serum-to-NELF transudation. AZD1222 induces short-lived increases to pre-existing nasal IgA levels in baseline-seropositive vaccinees. Vaccinees display a robust recall IgG response upon breakthrough infection, with overall magnitudes unaffected by time between vaccination and illness. Mucosal responses correlate with reduced viral loads and shorter durations of viral shedding in saliva.

Leishmania infantum infection does not affect the main composition of the intestinal microbiome of the Syrian hamster

BackgroundVisceral leishmaniasis (VL) is the most severe form of all leishmanial infections and is caused by infection with protozoa of Leishmania donovani and Leishmania infantum. This parasitic disease occurs in over 80 countries and its geographic distribution is on the rise. Although the interaction between the intestinal microbiome and the immune response has been established in several pathologies, it has not been widely studied in leishmaniasis. The Syrian hamster is the most advanced laboratory model for developing vaccines and new drugs against VL. In the study reported here, we explored the relationship between the intestinal microbiome and infection with L. infantum in this surrogate host.MethodsMale Syrian hamsters (120–140 g) were inoculated with 108 promastigotes of a canine-derived L. infantum strain or left as uninfected control animals. Infection was maintained for 19 weeks (endpoint) and monitored by an immunoglobulin G (IgG) enyzme-linked immunosorbent assay throughout the experiment. Individual faecal samples, obtained at weeks 16, 18 and 19 post-inoculation, were analysed to determine the 16S metagenomic composition (the operational taxonomic units [OTUs] of the intestinal microbiome and the comparison between groups were FDR (false discovery rate)-adjusted).ResultsLeishmania infantum infection elicited moderate clinical signs and lesions and a steady increase in specific anti-Leishmania serum IgG. The predominant phyla (Firmicutes + Bacteriodetes: > 90%), families (Muribaculaceae + Lachnospiraceae + Ruminococcaceae: 70–80%) and genera found in the uninfected hamsters showed no significant variations throughout the experiment. Leishmania infantum infection provoked a slightly higher—albeit non-significant—value for the Firmicutes/Bacteriodetes ratio but no notable differences were found in the relative abundance or diversity of phyla and families. The microbiome of the infected hamsters was enriched in CAG-352, whereas Lachnospiraceae UCG-004, the [Eubacterium] ventriosum group and Allobaculum were less abundant.ConclusionsThe lack of extensive significant differences between hamsters infected and uninfected with L. infantum in the higher taxa (phyla, families) and the scarce variation found, which was restricted to genera with a low relative abundance, suggest that there is no clear VL infection-intestinal microbiome axis in hamsters. Further studies are needed (chronic infections, co-abundance analyses, intestinal sampling, functional analysis) to confirm these findings and to determine more precisely the possible relationship between microbiome composition and VL infection.Graphical

Immunological evidence of an early seroconversion to oncogenic Merkel cell polyomavirus in healthy children and young adults.

Oncogenic Merkel cell polyomavirus (MCPyV) provokes a widespread and asymptomatic infection in humans. Herein, sera from healthy children and young adults (HC, n=344) aged 0-20 years old were evaluated for anti-MCPyV immunoglobulin G (IgG) and IgM antibodies employing a recently developed immunoassay. Serum MCPyV IgG data from healthy subjects (HS, n=510) and elderlies (ES, n=226), aged 21-65/66-100 years old, from our previous studies, were included. The anti-MCPyV IgG and IgM rates in HC sera were 40.7% and 29.7%, respectively. A lower prevalence of anti-MCPyV IgGs was found in HC aged 0-5 years old (13%) compared to 6-10 (52.3%), 11-15 (60.5%) and 16-20 years old (61.6%) cohorts. Age-stratified HCs exhibited similar anti-MCPyV IgM rates (27.9%-32.9%). Serological profiles indicated that anti-MCPyV IgGs and IgMs had low optical densities (ODs) during the first years of life, while IgM ODs appeared to decrease throughout young adulthood. A lower anti-MCPyV IgGs rate was found in HC (40.7%) than HS (61.8%) and ES (63.7%). Upon the 5-years range age-stratification, a lower anti-MCPyV IgGs rate was found in the younger HC cohort aged 0-5 years old compared to the remaining older HC/HS/ES cohorts (52.3%-72%). The younger HC cohort exhibited the lowest anti-MCPyV IgG ODs than the older cohorts. Low anti-MCPyV IgMs rates and ODs were found in the 21-25 (17.5%) and 26-30 (7.7%) years old cohorts. Our data indicate that, upon an early-in-life seroconversion, the seropositivity for oncogenic MCPyV peaks in late childhood/young adulthood and remains at high prevalence and relatively stable throughout life.

Prevalence of theDirect Antiglobulin Test and Its Clinical Impact on Multiply Transfused Thalassemia Patients: AProspective Study Conducted at aTertiary Care Center in Northern India.

This study was conducted to estimate prevalence of direct antiglobulin test (DAT) positivity and its impact on transfusion support in patients with thalassemia. The DAT testing was performed for patients with β-thalassemia who received transfusion from November 2021 to March 2022. Elution was done for DAT-positive samples. Of 180 patients, 21 (11.6%) were DAT positive. Immunoglobulin G (IgG) was present in 4 (19%) and IgG+C3d was present in 8 (38%). Only complement was present in 9 (42.8%) patients. The IgG-reactive DATs were associated with pan-reactive eluate. Patients who were DAT-positive had significantly higher levels of serum bilirubin, ferritin, and IgG than those who were DAT-negative. Autoantibody formation in multiply transfused thalassemia patients is common and merits equal attention as alloimmunization. It is particularly important as DAT-positive red bloodcells may undergo clinically significant hemolysis, which may increase the transfusion requirements with associated sequalae such as increased serum ferritin and splenomegaly.

Changes in serum total protein and immunoglobulin G concentrations and Brix percentages in neonatal Arabian foals from birth up to 21 days of age

The aim of this study was to evaluate changes in the serum immunoglobulin G (IgG) and serum total protein (STP) concentrations and serum Brix percentages of neonatal Arabian foals during first 3 weeks of life. Blood samples were collected from 12 apparently healthy foals by jugular venipuncture at birth and at 12-hours, 24-hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 and 21 days of age. Serum IgG and STP concentrations and Brix percentages were measured by the radial immunodiffusion assay, and digital STP and Brix refractometers, respectively. Based on the serum IgG concentrations measured at 24 h, two foals were diagnosed with failure of transfer of passive immunity (FTPI). While IgG concentrations were determined using the data of foals with adequate transfer of passive immunity, other calculations were made using the data of all foals. The mean IgG concentration of the foals increased from birth (<200 mg/dl) to 12 (2068.5 mg/dl) and 24 h (2184.7 mg/dl), and progressively decreased up to 21 days of age (1318.5 mg/dl). The serum IgG concentrations at 12 h were highly correlated with each of the IgG concentrations measured over the 21-day period. The serum IgG and STP concentrations and Brix percentages of the foals diagnosed with FTPI at 12 h did not reach the adequate strata over time. These results suggest that foals can be reliably tested for passive immunity status at 12 h after birth.

Hazelnut Skin in Ewes' Diet: Effects on Colostrum Immunoglobulin G and Passive Transfer of Immunity to the Lambs.

Passive immunity transfer has a pivotal role in newborn lambs, where the colostrum represents the primary source of immunoglobulins. This study hypothesized that the high content in polyphenolic compounds, mono- and poly-unsaturated fatty acids, and vitamin E of hazelnut skin affects blood and colostrum immunoglobulin G (IgG) concentration and related gamma-glutamyl-transferase (GGT) and lactate dehydrogenase (LDH) levels in sheep and their lambs. In the last 45 days of pregnancy, ewes were divided into a control (CTR) and a hazelnut skin supplemented group (HZN). Blood and colostrum were collected from ewes and lambs before the first suckling, at 24 and 48 h after birth, then IgG concentration, GGT and LDH activity levels were measured. IgG concentration in the colostrum and in lamb's serum were significantly greater in HZN than CTR. No significant difference was detected for ewe's blood. A significant positive correlation was found between IgG and GGT in lambs' serum and colostrum, between IgG and LDH, as well as between GGT and LDH in lambs' serum and colostrum. Our results suggest that hazelnut skin supplementation influences IgG colostrum concentration, with improved immune passive transfer to the suckling lambs. The transfer of maternal derived immune factors is confirmed by the GGT and LDH enzyme activity levels.

Alpha-aminoisobutyric acid incorporated peptides for the construction of electrochemical biosensors with high stability and low fouling in serum

An effective strategy to construct low fouling electrochemical biosensors for assaying serum biomarkers was proposed based on specially designed α-aminoisobutyric acid (Aib) incorporated peptides. The Aib-peptides were designed to be of antifouling properties, and at the same to incorporate Aib residues in their interior to enhance the hydrolytic stability. In order to construct the electrochemical biosensor, two kinds of Aib-peptides labelled with biotin were modified on the electrode surface: One with cysteine terminal for easy attachment to the electrode modified with gold nanoparticles, the other with unique terminal peptide sequence for specific binding of immunoglobulin G (IgG), and they were connected through the streptavidin-biotin affinity system. Owing to the interposition of Aib residues, the peptides as well as the constructed biosensors showed excellent antifouling performances and enhanced stability against enzymatic degradation in serum. Furthermore, the IgG biosensor constructed with the Aib-peptides displayed a very low detection limit (29.5 pg mL−1) and a broad linear range (100 pg mL−1 - 10 μg mL−1), and it was able to assay IgG in clinical human sera with decent accuracy and reliability. This strategy provides a new path for the construction of stable antifouling biosensors based on functional peptides for practical biomarker assaying in real clinical samples.

Energy Trial in Warm Autoimmune Hemolytic Anemia (wAIHA): Design of a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nipocalimab, an FcRn Blocker

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare condition characterized by the premature destruction of red blood cells (RBCs) mainly in the presence of pathogenic immunoglobulin G (IgG) autoantibodies that preferentially bind to RBCs at 37°C, resulting in extravascular hemolysis of these RBCs in the spleen (or liver). Patients with wAIHA can experience acute or chronic worsening of anemia, increased risk of thromboembolic events, and premature death. Innovative targeted therapies that address the underlying pathogenesis of wAIHA are needed, as there is currently no approved treatment for this disease. Nipocalimab is a high affinity, fully human, aglycosylated, effectorless IgG1 monoclonal antibody that targets the neonatal Fc receptor (FcRn) to lower circulating IgG levels, including pathogenic autoantibodies. Nipocalimab is being evaluated across multiple IgG-mediated diseases. A completed phase 2 study in patients with generalized myasthenia gravis demonstrated rapid, durable total serum IgG and pathogenic IgG autoantibody reductions and meaningful clinical response [Guptill J, et al. AAN 2021. Presentation 2157]. Aim: Describe the rationale and study design of ENERGY, an ongoing, adaptive, phase 2/3 multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of nipocalimab compared with placebo in patients with wAIHA (NCT04119050). Methods: Subjects ≥18 years of age who have been diagnosed with primary or secondary wAIHA and are currently receiving treatment for wAIHA or have previously received treatment for wAIHA will be included in the study. Subjects with cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria will be excluded. Stable doses of corticosteroids or immunosuppressants will be allowed. Approximately 111 patients will be randomized 1:1:1 to receive nipocalimab at two different dose schedules or placebo. Following completion of 24 weeks of double-blind treatment, patients may enter an open-label extension period to receive nipocalimab for 144 weeks with a follow-up period of 6 weeks after last assessment. Results: ENERGY will include approximately 160 sites across 19 countries, including Brazil, Canada, China, Czech, Egypt, France, Germany, Greece, Hungary, Japan, Israel, Malaysia, Netherlands, Italy, Poland, South Korea, Spain, the United Kingdom, and the United States. The primary endpoint is percentage of participants achieving durable response of improvement in hemoglobin (Hgb). The secondary endpoints include change from baseline in the total score from the Functional Assessment of Chronic Illness Therapy-Fatigue Scale, corticosteroid dose reduction from baseline, and normalization of hemolytic markers. Conclusion/Summary: The results of ENERGY have the potential to identify a novel treatment option to address the significant unmet needs of patients with wAIHA. Enrollment is ongoing in this clinical trial.

Ultra-early weaning alters growth performance, hematology parameters, and fecal microbiota in piglets with same genetic background

Piglets with the same genetic background were used to investigate the effects of different lengths of suckling period on growth performance, hematology parameters, and fecal microbiota. All piglets were born by a sow (Landrace×Yorkshire). On day 14 postpartum, a total of 16 piglets [Duroc×(Landrace×Yorkshire)] with a similar initial body weight (2.48 ± 0.25 kg) were randomly assigned into two groups with four replicates per group, two pigs per replicate pen (one barrow and one gilt). On day 14 of age, experiment started, piglets from the first group were weaned (14W), whereas the others continued to receive milk until day 28 of age (28W). The experiment completed on day 70 of age, last 56 days. Growth performance parameters including body weight, average daily gain, feed intake, feed efficiency, and growth rate and hematology parameters including immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), albumin, globulin, and total protein were measured in this study. Additionally, a technique of 16S rRNA gene sequencing was used to analyze fecal microbiota for revealing how the changes in the lengths of suckling period on intestinal microbiota. We found that ultra-early weaning impaired growth performance of piglets, whose worse body weight, average daily gain, feed intake, feed efficiency, and growth rate were observed in 14W group at all measured timepoints in comparison with those in 28W group (P < 0.05). Moreover, higher contents of serum IgA (P = 0.028), IgG (P = 0.041), and IgM (P = 0.047), as well as lower contents of serum albumin (P = 0.002), albumin-to-globulin ratio (P = 0.003), and total protein (P = 0.004), were observed in 14W group in comparison with those in 28W group on day 28 of age, but not on day 70 of age. High-throughput pyrosequencing of 16S rRNA indicated that the intestinal microbiota richness in 14W group was lower than that in 28W group (P < 0.05); moreover, in comparison with 28W group at all sampling timepoints, fecal microbiota in 14W group showed more beneficial bacteria and fewer pathogenic bacteria (P < 0.05). Therefore, we considered that ultra-early weaning had positive effects on immune status and fecal microbiota composition in piglets, but negative effects on growth performance and fecal microbiota abundance.

ODP509 Proof-of-concept, Multicenter, Open-Label Phase 2a Study of Batoclimab in Active and Moderate-to-Severe Thyroid Eye Disease

Abstract In thyroid eye disease (TED), immunoglobulin G (IgG) autoantibodies target thyrotropin receptors (TSHR) on the thyroid gland causing Graves’ disease. These TSHR-Ab also bind to the TSHR on orbital fibrocytes, inducing inflammation and hyaluronan production, resulting in extraocular muscle swelling and orbital fat expansion, causing the clinical manifestations of TED. Batoclimab (IMVT-1401) is a selective, fully human monoclonal antibody with high affinity for the IgG binding site on the neonatal Fc receptor (FcRn). Normally, the half-life of IgG is extended by FcRn-mediated recycling from lysosomal degradation. By competitively binding to the IgG binding site on FcRn, batoclimab blocks FcRn-mediated recycling of IgG, resulting in increased elimination and decreased levels of IgG. Batoclimab thus has the potential to provide clinical benefit for TED patients by reducing the level of pathogenic IgG anti-TSHR-Ab. In this open-label, multicenter, phase 2a study (NCT03922321), subjects with anti-TSHR-Ab positive, moderate-to-severe TED with a clinical activity score (CAS) ≥4 received weekly subcutaneous (SC) injections of batoclimab for six weeks (680 mg for two weeks followed by 340 mg for four weeks). Subjects were monitored for up to an additional 11 weeks. Safety and tolerability were assessed throughout the study. Pharmacodynamic changes in serum IgG and anti-TSHR-Ab were monitored weekly. Clinical efficacy was assessed weekly by response rate for proptosis (≥2 mm reduction in study eye without a deterioration in the other eye). The study eye was defined as the eye with greater proptosis at baseline. CAS response was defined as having a CAS score of 0 or 1. Seven subjects enrolled and completed this study (baseline mean [SD] age 56.7 [14.9] years, CAS 5.4 [1.1], proptosis 23.1 [3.3] mm). Serum IgG and anti-TSHR-Ab were reduced by a mean (SD) of 64.8% (17.7) and 56.7% (33.6), respectively at Week 6 compared to baseline. Similar reductions were also observed with each IgG subclass. Three of seven subjects were proptosis responders and four subjects were CAS responders. Three of seven subjects were joint responders for both proptosis and CAS. All adverse events (AEs) were mild to moderate in severity and no participant reported serious AEs or discontinuation due to AE. The most common AEs were increased lacrimation, fatigue, and dizziness (n=2 for each).There was a reversible reduction in serum albumin while on treatment which returned to normal levels in all subjects by the end of the study. In conclusion, batoclimab reduced serum IgG and especially the pathogenic anti-TSHR-Ab with an acceptable tolerability profile. Approximately half of study subjects demonstrated improvement in ophthalmologic assessments with six weeks of treatment. Together, these results support further evaluation of SC batoclimab as a therapeutic option for patients with TED. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF35 | PSAT269 Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase 2b Study of Batoclimab in Active and Moderate-to-Severe Thyroid Eye Disease

Abstract Clinical manifestations of thyroid eye disease (TED) are mainly caused by the binding of immunoglobulin G (IgG) thyrotropin receptors (TSHR) autoantibodies (TSHR-Ab) on orbital fibroblasts. Batoclimab (IMVT-1401) is an anti-neonatal Fc receptor (FcRn) human monoclonal antibody that prevents normal IgG recycling, leading to reduced levels of circulating IgG. Thus, batoclimab may provide benefit for patients with TED by reducing pathogenic anti-TSHR-Ab. In this Phase 2b, double-blind, randomized study (NCT03938545), subjects with active and moderate-to-severe TED received weekly subcutaneous (SC) injections of batoclimab (680mg, 340mg, 255mg) or placebo for 12-weeksSixty-five subjects were randomized and received batoclimab (680mg [n=18], 340mg [n=19], 255mg [n=10]) or placebo (n=18). Recruitment and treatment were stopped because of an unanticipated increase in LDL cholesterol levels, not included in subject informed consent. Hence, forty-five of 77 planned subjects completed the 12-week treatment period. Serum IgG and anti-TSHR-Ab were reduced from baseline to Week-12 with batoclimab (680mg [-77.9%; -65.5%], 340mg [-65.8%; -70.1%], 255mg [-56.6%; -42.1%]) versus placebo (-4.67%; -3.23%), respectively. Substantial reductions were also observed at Week-12 in stimulatory anti-TSHR-Ab. Fifty-one of 65 subjects had proptosis ≥ upper level of normal at baseline. At Week-12 (primary outcome), greater proportions of 680mg (30%; p=0.2197) and 340mg (30.8%; p=0.1311) subjects were proptosis responders (≥2mm reduction) versus placebo (8.3%). Absolute risk reduction (ARR [95% CI]) versus placebo was 21.4 (-11.3, 54.1) for 680mg and 24.2 (-4.8, 53.2) for 340mg at Week 12. Earlier proptosis responses were statistically different from placebo for 680mg at Weeks-four (35.7%; ARR [95% CI] 36.0 [10.9, 61.1]), five (42.9%; 43.0 [17.1, 68.9]), and 11 (41.7%; 34.5 [3.4, 65.6]) and for 340mg at Weeks-five (29.4%; 29.6 [7.9, 51.3]), nine(35.7%; 30.6 [3.0, 58.2]), and 11 (46.2%; 40.2 [10.2, 70.1]) (all p&amp;lt;0.05). Changes in clinical activity at Week-12 were not significantly different from placebo.The proportion of subjects with an adverse event (AE) were similar across treatment groups; most were mild or moderate in severity. Two subjects reported serious AEs not related to treatment (optic neuropathy, autoimmune encephalitis [occurring after treatment period]). No subjects withdrew from the study due to an AE during the 12-week treatment period. There was a reversible dose-dependent reduction in serum albumin during the treatment period. Post-hoc lipid analysis demonstrated a reversible increase in mean serum LDL during treatment (680-mg: 58.7%; 340-mg: 30.8%; 255-mg: 19.0%) vs placebo (-3.9%),.In conclusion, batoclimab reduced circulating IgG and especially the pathogenic anti-TSHR-Ab. Although the proptosis response was not statistically significant at the primary endpoint, significance was seen at earlier time points. This is probably related to early study termination which reduced the numbers of patients available for efficacy assessment at the primary endpoint. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.

Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation

Antibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSAs) are associated with a higher risk of AMR, not all patients with DSAs develop rejection, suggesting that the characteristics of alloantibodies determining their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we apply systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR-binding properties. Levels of afucosylated anti-A2 antibodies are elevated in seropositive patients, especially those with AMR, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 drives potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells, and greater cytotoxicity against HLA-A2+ cells mediated by natural killer (NK) cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and contribute to pathogenesis.

Impact of saline infusion and citrate infusion rate during donor plasmapheresis.

The purpose of our research was to evaluate the effects of saline infusion to counteract incidents of severe hypotension during donor plasmapheresis (DP; synonym with plasma donation), and on immunoglobulin G (IgG) content in collected plasma, and on donor hematological values. It examines the clearance (Cl) of IgG during DP without saline to calculate the distribution of citrate and citrate infusion rate (CIR) during DP. It is based on three studies: an observation of saline infusion in donors with severe drops in blood pressure at DP, and two crossover trials of 32 repeat plasma donors each on saline infusion during DP. We observed 50 cases with a significant drop of mean systolic blood pressure ≤90 mm Hg in 1 year, predominantly in young, female first-time donors. In trial 1, there was a reduction of IgG concentration in collected plasma related to the average IgG serum concentration without saline to 85.5% vs to 80.5% with saline (P< .001). In trial 2, there was an important 11%-12% increase of the donor hematological values without saline during DP. An average of 84.6% of citrate was removed in retained plasma; our calculated minimal CIR of 0.16 ± 0.17 mg/kg/min was confirmed by other empirical studies. Our research has led to significant improvements in the practice of DP: (a) Saline should be infused at DP as clinically indicated in agreement with the donor. (b) Young, female first-time donors require special care. (c) The long-time effects of minimal amounts of citrate on bone metabolism are improbable.

Serum antibodies to periodontal pathogens are related to allergic symptoms.

The association between periodontitis and allergic symptoms has been investigated. However, the difference in immune signatures between them remains poorly understood. This cross-sectional study assessed the relationship between serum immunoglobulin G (IgG) antibodies to periodontal pathogens and allergic symptoms in a nationwide population cohort. Two phases of the Third National Health and Nutrition Examination Survey (NHANES III) were used as discovery dataset (n =3700) and validation dataset (n=4453), respectively. Based on the antibodies against 19 periodontal pathogens, we performed an unsupervised hierarchical clustering to categorize the population into three clusters. In the discovery dataset, cluster 1 (n=2847) had the highest level of IgG antibodies, followed by clusters 2 (n=588) and 3 (n=265). Data on allergic symptoms (asthma, hay fever, and wheezing) were obtained using a self-reported questionnaire. Survey-weighted multivariable logistic regression evaluated the association between these clusters and allergic symptoms. In the discovery dataset, the participants with lower levels of antibodies to periodontal pathogens exhibited a higher risk of asthma (odds ratio [OR]cluster 3vs. cluster 1 =1.820, 95% confidence interval [CI]: 1.153-2.873) and wheezing (ORcluster 3vs. cluster 1 =1.550, 95% CI: 1.095-2.194) compared to those with higher periodontal antibodies, but the non-significant association with hay fever. Consistent results were found in the validation dataset. Serum IgG titers to periodontal pathogens were inversely associated with the risk of asthma and wheezing, suggesting the potentially protective role against allergic conditions.

Association between serum baseline C1q and IgG levels and the efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma: a retrospective study

Background To assess the clinical value of serum complement component 1q (C1q) and immunoglobulin G (IgG) levels in predicting the response to combined immunotherapy in patients with esophageal squamous cell carcinoma. Methods We conducted a retrospective study of 44 patients with esophageal squamous cell carcinoma who received combined immunotherapy in our hospital. Serum IgG and C1q levels were collected before and three weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. Results Twenty seven patients (61.4%) showed partial response (PR), 13 (29.5%) stable disease (SD), and 4 (9.1%) progressive disease (PD). None of the patients presented complete response (CR). The PR group displayed lower IgG and higher C1q levels both before and after immunotherapy than patients showing SD or PD. The IgG reduction (59.3%) and C1q increment (70.3%) in the PR group three weeks post-treatment were significantly larger than those in patients showing SD or PD. Moreover, the pretreatment C1q level and the post-treatment change of C1q levels were strongly associated with the immunotherapy response. Conclusions High pre- and post-treatment C1q levels and reduced post-treatment IgG levels correlate with efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma. Serum baseline C1q level may predict immunotherapy response in such patients.

Maintenance of Antibody Response in Egyptian Healthcare Workers Vaccinated with ChAdOx1 nCoV-19 Vaccine during Delta and Omicron Variants Pandemic: A Prospective Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a constantly evolving virus, resulting in an increased burden on the existing COVID-19 vaccines. Healthcare workers (HCWs) are the first line of defense against the coronavirus disease 2019 (COVID-19) pandemic and have been prioritized among the risk categories receiving the COVID-19 vaccine. This work aimed to investigate the maintenance of antibody response of the Oxford–AstraZeneca vaccine (ChAdOx1/nCoV-19). Methods: Anti-spike immunoglobulin G (IgG) was measured at baseline point (immediately prior to vaccination) and 12- and 24-week (w) points following vaccination. Adverse reactions to the vaccine were reported. Participants were followed up for the incidence of COVID-19 during the 12 w interval between vaccination doses for 24 w after the second dose. Results: A total of 255 HCWs participated in the study. Prior to vaccination, 54.1% experienced COVID-19, 88.2% were seropositive after the first dose, while seropositivity reached 95.7% after the second dose. Following the first and second doses, the anti-spike IgG serum level was significantly higher in subjects with past COVID-19 than in others (p < 0.001 and =0.001, respectively). Conclusions: The Oxford–AstraZeneca vaccine is generally safe and provides a highly effective long-term humoral immune response against the Delta and Omicron variants of SARS-CoV-2.

Denatured bovine serum albumin hydrogel-based electrochemical biosensors for detection of IgG.

Anantifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor. Due to the large specific surface area and good electrical conductivity of MXene, the sensitivity of the biosensor is significantly enhanced. The biosensor at a working potential of around - 0.18V (vs. Ag/AgCl) provides a wide linear detection range (0.1 ng/mL to 10 µg/mL)for IgGwith alimit of detection of 23pg/mL (3σ/k). The result is consistent with that obtained from the commercial enzyme-linked immunosorbent kit. Compared with BSA, which is usually used as a passivator or blocker for biosensing platforms, the hydrogel formed through the peptide chain obtained from BSA with good hydrophilicity can provide a better antifouling sensing surface to resist nonspecific adsorption. The prepared biosensor can quantitatively detect the concentration of IgG in complex human serum with high sensitivity. Thus, the antifouling sensing surface constructed without expensive antifouling materials and complex process is expected to develop as a variety of electrochemical biosensors and used for the clinical testing of biomarkers. Graphical abstract An antifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor.

Assaying the concentration of immunoglobulin G in colostrum from females postpartum and serum from neonatal calves of buffaloes (Bubalus bubalis)

Neonatal ruminants are born without any humoral immunity due to lack of placental transfer of immunoglobulins during gestation. This predisposes the newborn buffalo calves to a high incidence of morbidity and mortality on exposure to infectious agents. Colostrum is the first milk produced by the females after calving and is a rich source of immunoglobulins, especially immunoglobulin G (IgG). The immunocompetence of the neonates can be boosted by feeding them sufficient amount of good quality colostrum within a few hours after birth. Optimal colostrum management at a farm not only reduces the occurrence of diseases among the younger stock but also enhances their growth performance and productivity once they are adults. In the present study, eighty animals at a Murrah buffalo farm were screened for the concentration of IgG in the colostrum collected from recently parturated females and in the serum collected from their calves within 6 to 12 h of colostrum consumption to determine the status of transfer of passive immunity. Indirect ELISA was used to estimate the IgG levels. The overall mean (range) of colostral and serum IgG concentration was found to be 50.44±3.36 (12.71 to 227.78) and 10.85±0.62 (0.25 to 19.88) mg/ml, respectively for all the 80 animals. Routine screening of buffaloes, in a similar way, will help to reduce calf deaths due to immunodeficiency.

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray.

Background: Inflammation plays a key role in the progression of atherosclerotic plaque for peripheral artery disease (PAD). Immunoglobulin G (IgG) glycosylation could modulate immunological effector functions and has been explored as biomarkers for various diseases. Methods: Lectin microarray was applied to analyze the expression profile of serum IgG glycosylation in patients with lower-extremity peripheral artery disease (LEPAD), carotid artery stenosis (CAS), abdominal aortic aneurysm (AAA), and healthy controls. Lectin blot was performed to validate the differences. Results: SNA (Sambucus nigra agglutinin) binding (preferred sialic acid) was significantly higher in the LEPAD (3.21 ± 2.06) and AAA (3.34 ± 2.42) groups compared to the CAS (2.47 ± 1.45) group. Significantly higher binding levels of ConA (Concanavalin A) (preferred mannose) and PSA (Pisum sativum agglutinin) (preferred fucose) were also observed in LEPAD compared to CAS patients. Among LEPAD patients, a significant lower binding level of Black bean crude (preferred GalNAc) was present for dyslipidemia patients. A higher binding level of MNA-M (Morniga M agglutinin) (preferred Mannose) and Jacalin-AIA (Artocarpus integrifolia agglutinin) (preferred Galβ3GalNAc) was observed for Fontaine severe patients. Higher binding levels of PHA-E (Phaseolus vulgaris Erythroagglutinin) and PHA-L (Phaseolus vulgaris Leucoagglutinin) (preferred Galβ4GlcNAc) were observed for diabetic patients, and higher binding of ASA (Allium sativum agglutinin) (preferred Mannose) was present in patients with hypertension. The level of high-sensitivity C-reactive protein (hsCRP) was positively associated with LTL (Lotus tetragonolobus lectin) (r = 0.44), PSA (r = 0.44), LCA (Lens Culinaris agglutinin) (r = 0.39), SNA (r = 0.57), and CSA (Cytisus sscoparius agglutinin) (r = 0.56). For CAS, symptomatic patients had lower binding levels of AAL (Aleuria aurantia lectin) (preferred fucose) and IAA (Iberis amara agglutinin) (preferred GalNAc). Blood total cholesterol level was positively associated with SNA-I (r = 0.36) and SBA (Soybean agglutinin) (r = r = 0.35). Creatinine levels were positively associated with lectins including, but not limited to, MNA-M (r = 0.42), CSA (r = 0.45), GHA (Glechoma hederacea agglutinin) (r = 0.42), and MNA-G (Morniga G agglutinin) (r = 0.45). Conclusion: LEPAD patients had increased IgG binding levels of SNA and ConA compared to CAS, which could provide potential diagnostic value. Fontaine severity was associated with Mannose-rich IgG N-glycan, while diabetic LEPAD correlated with bisecting GlcNAc. The levels of hsCRP and creatinine were positively associated with IgG fucosylation and galactosylation. Changes in IgG glycosylation may play important roles in PAD pathogenesis and progression.

Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?

ObjectiveFatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8–25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia. MethodsPwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run. Results97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (–1.6, 95%CI –2.7 - –0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2–1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8–1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness. ConclusionsWe found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively.