Specific IgG Antibody Concentrations Research Articles

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy.

M-type phospholipase A2 receptor (PLA2R) is the major autoantigen in adult idiopathic membranous nephropathy (IMN). Although reactive epitopes in the PLA2R domains have been identified, the clinical value of these domains recognized by anti-PLA2R antibodies remains controversial. Accordingly, this study aimed to quantitatively detect changes in the concentrations of different antibodies against epitopes of PLA2R in patients with IMN before and after treatment to evaluate the clinical value of epitope spreading. Highly sensitive time-resolved fluorescence immunoassay was used to quantitatively analyze the concentrations of specific IgG and IgG4 antibodies against PLA2R and its epitopes (CysR, CTLD1, CTLD6-7-8) in a cohort of 25 patients with PLA2R-associated membranous nephropathy (13 and 12 in the remission and non-remission groups, respectively) before and after treatment, and the results were analyzed in conjunction with clinical biochemical indicators. The concentration of specific IgG (IgG4) antibodies against PLA2R and its epitopes (CysR, CTLD1 and CTLD6-7-8) in non-remission group was higher than that in remission group. The multipliers of elevation of IgG (IgG4) antibody were 5.6(6.2) fold, 3.0(24.3) fold, 1.6(9.0) fold, and 4.2(2.6) fold in the non-remission/remission group, respectively. However, the difference in antibody concentrations between the two groups at the end of follow-up was 5.6 (85.2), 1.7 (13.1), 1.0 (5.1), and 1.5 (22.3) times higher, respectively. When detecting concentrations of specific IgG antibodies against PLA2R and its different epitopes, the remission rate was 66.67% for only one epitope at M0 and 36.36% for three epitopes at M0. When detecting concentrations of specific IgG4 antibodies against PLA2R and its different epitopes, the remission rate was 100.00% for only one epitope at M0 and 50.00% for three epitopes at M0. A trivariate logistic regression model for the combined detection of eGFR, anti-CTLD678 IgG4, and urinary protein had an AUC of 100.00%. Low concentrations of anti-CysR-IgG4, anti-CTLD1-IgG4, and anti-CTLD6-7-8-IgG4 at initial diagnosis predict rapid remission after treatment. The use of specific IgG4 against PLA2R and its different epitopes combined with eGFR and urinary protein provides a better assessment of the prognostic outcome of IMN.

Phase I Pharmacokinetics Study of Drug «COVID-globulin» (Specific Human Immunoglobulin Against COVID-19)

Introductio n. Coronavirus infection is an acute viral disease with a predominant lesion of the upper respiratory tract caused by an RNA-containing virus of the Coronaviridae family. However, it is known that neutralizing antibodies play an important role in antiviral therapy because they effectively inhibit the reproduction of viruses and reduce the severity of the disease. Polyclonal antibodies contained in convalescent plasma are usually used as emergency therapy for emerging infectious diseases. In this aspect, the use of a human immunoglobulin G preparation containing specific antibodies to SARS-CoV-2 ("COVID-globulin") appears to be safer and more effective. Aim. The aim is pharmacokinetics study of drug "COVID-globulin" (specific human immunoglobulin against COVID-19, solution for infusions, not less than 160 anti-COVID units/mL (ACU/mL), JSC "NPO Microgen", owner of the registration certificate of JSC "Natsibio", Russia), in addition to standard therapy for the treatment of patients with middle-grade COVID-19. Materials and methods. The clinical and analytical stages of the study of the pharmacokinetics of drug "COVID-globulin", as well as the analysis of the safety and parameters of pharmacokinetics were carried as part of a clinical study of the safety, tolerability and pharmacokinetics of the drug immunoglobulin ("COVID-globulin"), not less than 160 anti-COVID units/mL (ACU/mL), JSC "NPO Microgen", owner of the registration certificate of JSC " Natsibio", Russia. Quantitative determination of antibody concentrations against SARS-CoV-2 was carried out by enzyme-linked immunosorbent assay using spectrophotometric detection in the visible range of the spectrum on an automatic plate enzyme-linked immunosorbent assay analyzer Lazurite (Dynex Technologies Inc., USA). The calculation of pharmacokinetic parameters was carried out using the Microsoft Excel package with an extension for pharmacokinetic analysis Boomer (Department of Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92606, USA). Results and discussion. No serious adverse events were reported in the study, and the only adverse event that resulted in a volunteer withdrawing from the study was not related to the use of the drug. The pharmacokinetic parameters of the drug "COVID-globulin" were calculated for two batches of drugs. The pharmacokinetics of the "COVID-globulin" (the content of antibodies to SARS-CoV-2 – 330 ACU/ml) was assessed on a sample of 8 volunteers. The maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 25.46 ± 8.71 ACU/ml (Mean ± SD, where Mean is the arithmetic mean, SD is the standard deviation). The median value of the time to maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 0.25 hours. Specific IgG antibodies to the SARS-CoV-2 virus were eliminated from blood plasma with a half-life value 266.89 ± 59.92 hours. The pharmacokinetics of the "COVID-globulin" (the content of antibodies to SARS-CoV-2 – 250 ACU/ml) was assessed on a sample of 15 volunteers. The maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 20.93 ± 3.82 ACU/ml. The median value of the time to maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 0.25 hours. Specific IgG antibodies to the SARS-CoV-2 virus were eliminated from blood plasma with a half-life value 295.56 ± 50.68 hours. Conclusion. According to the results of the study, the safety profile of the drug "COVID-globulin" is assessed as favorable. Based on the concentrations of specific IgG antibodies to the SARS-CoV-2 virus obtained during the analytical stage of the study, the main pharmacokinetic parameters were calculated, and the average pharmacokinetic profiles of the test drug "COVID-globulin" were plotted after a single injection. The results obtained were the basis for the subsequent phases of clinical trials of the drug "COVID-globulin".

Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein–specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

Age-Related Dynamics in Post-Vaccine Antibody Immune Response to Diphtheria and Tetanus Toxoid in Bulgarian Subjects

Abstract In this study, we investigated the age-related dynamics in post-vaccine humoral immunity to diphtheria (DT) and tetanus (TT) toxoids in the Bulgarian population. In addition, we attempted to correlate the titers of specific antibodies with the predisposition to more common infectious pathology among our study participants. The 208 individuals tested were divided into five age groups: 0-4, 4-6, 6-12, 12-17 and 17-66 years, based on the vaccines received according to the immunization schedule in Bulgaria. Vaccine response was determined by measuring the concentrations of specific IgG antibodies using commercial ELISA kits. Sufficient protective levels of diphtheria (> 0.1 IU/mL) and tetanus (> 0.15 IU/mL) antitoxin were detected in 63.5% and 85.1% of all subjects, respectively. The highest rates of protection against both TT (94.3%) and DT (79.2%) were observed in the youngest age group (0-4 years). We also observed a relatively high rate of insufficient protection (< 0.1 IU/ml) against diphtheria (36% of individuals tested across all age groups) in comparison to tetanus (14.9% of all subjects). The rate of insufficient protection against both antigens was higher among children with frequent infections. Moreover, 77.1% of the individuals having low antibody titers against the highly immunogenic tetanus toxoid, also had low levels of diphtheria antibodies. The level of seroprotection is better for tetanus than for diphtheria toxoid at any age. In conclusion, our data provide information on the level of immunity to diphtheria and tetanus among vaccinated individuals in Bulgaria and allows for the identification of persons suspected of having an immune deficiency. Additional investigations are needed in order to provide reliable recommendations for the national vaccine program and personalized vaccinations.

Application of benchmark analysis for mixed contaminant exposures: Mutual adjustment of perfluoroalkylate substances associated with immunotoxicity.

BackgroundDevelopmental exposure to perfluorinated alkylate substances (PFASs) is associated with deficient IgG antibody responses to childhood vaccines. As this immunotoxicity outcome may represent a critical effect, calculation of benchmark dose (BMD) results would be useful for defining protective limits of exposure. However, exposures to the major PFASs that are associated with this adverse effect are interrelated, and mutually adjusted BMD results would be desirable.MethodsWe carried out BMD calculations on prospective data from two prospective birth cohort studies from the Faroe Islands with a total of 1,146 children. Exposure data included serum concentrations of five major PFASs at birth and at age 5 years and, as outcome parameters, the serum concentrations of specific IgG antibodies against tetanus and diphtheria at ages 5 and 7. We calculated the BMDs and their lower confidence bounds (BMDLs) and included mutual adjustment for five major PFASs. BMD and BMDL were expressed in terms of the serum concentration of the PFASs.ResultsThe BMDLs for the immunotoxicants were of similar magnitude before and after adjustment. As compared to linear dose-response models, the PFASs showed lower results for a piecewise linear model, which also provided a slightly better fit. Weaker associations with the antibody outcomes were observed after adjustments due to the correlation between the PFASs. However, while the adjustments resulted in elevated BMD results and p values, the BMDL values were not materially changed.ConclusionsAdjustment for co-exposure to a related immunotoxicant increased both the BMD values and their standard errors, though affected the BMDL values only to a negligible extent. Thus, when correlated toxicants appear to affect the same outcome and none of them is known a priori to be solely responsible, all exposures may be considered responsible in BMD calculations. Our BMDL results, both before and after adjustment are generally below current exposure levels and therefore suggest that all five perfluorinated substances should attract regulatory attention, at least until additional evidence shows otherwise.

Seroprevalences of Specific IgG Antibodies to Measles, Mumps, and Rubella in Korean Infants.

In this study, the seroprevalences of measles, mumps, and rubella antibodies in infants were determined to assess the immunization strategy and control measures for these infectious diseases. Serum samples from infants < 1 year of age and their mothers were collected to measure the concentrations of specific IgG antibodies to measles, mumps, and rubella by enzyme-linked immunosorbent assay. For selected infant serum samples, measles-specific neutralizing antibody levels were determined by using the plaque reduction neutralization test. The sera from 295 of infants and 80 of their mothers were analyzed. No infants had past measles, mumps, or rubella infections. Almost all infants < 2 months of age were positive for measles and rubella IgG antibodies. However, seroprevalence of measles and rubella antibodies decreased with age, and measles IgG and rubella IgG were barely detectable after 4 months of age. The seroprevalence of mumps antibodies was lower than that of measles and rubella antibodies in infants ≤ 4 months old, and mumps IgG was barely detectable after 2 months of age. The seropositivity of measles-specific neutralizing antibody was 63.6% in infants aged 2 months and undetectable in infants ≥ 6 months old. Because the seropositivity rates of measles, mumps, and rubella antibodies were low after the first few months of age in Korean infants, active immunization with vaccines is strongly recommended for infants aged 6–11 months when measles is epidemic. Timely administration of the first dose of measles-mumps-rubella vaccine at 12 months of age should be encouraged in non-epidemic situations.

Naturally acquired immunity to Haemophilus influenzae type B in healthy Cuban children

We have evaluated the prevalence of antibody to immunogenicity of Haemophilus influenzae type b (Hib) in a group of 4 to 5 years old healthy children, who were too old to be included in the first vaccinated cohort when Hib vaccination begun in Cuba in 1999. Serum capsular polysaccharide specific IgG antibody concentrations were measured in 974 healthy children, between February and May 2002. The prevalence of Hib nasopharyngeal carriage was also estimated. The majority of children (99.7%) had more than 1 microg/ml of antibody. The preliminary report of the nasopharyngeal cultures was positive for H. influenzae in 16 children, but in only one was confirmed as Hib after serotyping (0.1% Hib nasopharyngeal carrier). These results provide evidence that in Cuba the natural active immunity to Hib can be acquired at an early age.

Antibody response to pneumolysin and to pneumococcal capsular polysaccharide in healthy individuals and Streptococcus pneumoniae infected patients

Background: Animal experiments have shown that antibodies against capsular polysaccharide enhance phagocytosis of pneumococcal bacteria and that antibodies against pneumolysin are anti-inflammatory and prevent pneumococcal invasion. It is not known if an antibody response to pneumolysin can be acquired from natural exposure to pneumococcal bacteria or how the concentration of pneumolysin antibody at the mucosal surface compares with that of antibodies against pneumococcal capsular polysaccharide. This study used an equal potency method to measure specific antibody concentrations against pneumolysin and pneumococcal capsular polysaccharides in order to facilitate comparative estimates of concentrations in saliva and serum. The results may provide experimental information as a basis for an improved pneumococcal vaccine strategy. Results: Healthy individuals had higher IgM and IgG antibody concentrations against capsular polysaccharide than against pneumolysin in both saliva and serum, but for IgA the converse was true. Patients with acute pneumococcal infection had significantly lower concentrations of specific IgG antibodies against both antigens than the healthy group. These patients also had significantly higher concentrations of IgM antibody against both antigens than the healthy control group. Discussion: Healthy individuals acquire a comparatively lower concentration of antibody to pneumolysin than to pneumococcal capsular polysaccharides from natural exposure to pneumococcal bacteria. Patients infected by pneumococcal bacteria have lower specific IgG antibody concentrations to both antigens than healthy individuals. These findings support the view that pneumolysin could potentially be used as a vaccine. For enhanced effectiveness, it could be used as a supplement to Pneumovax ®II rather than as a replacement. The two acquired antibodies, i.e. to pneumolysin and to capsular polysaccharide, could then play their protective roles at different stages in the course of pneumococcal infection, and together contribute to an effective immune defence against Streptococcus pneumoniae.

Opsonophagocytic activity against Streptococcus pneumoniae type 19F in allogeneic BMT recipients before and after vaccination with pneumococcal polysaccharide vaccine

Opsonophagocytic activity (OPA) of pneumococcal polysaccharide (Pnc PS) antibodies in vitro, a measure of antibody functional activity, usually correlates with specific IgG antibody concentrations measured by an EIA method. In order to investigate the functional activity of specific Pnc PS antibodies, we determined IgG antibodies to Pnc PS type 19F by an EIA method and OPA against Pnc type 19F by a killing assay in a randomized study, where 23 adult allogeneic BMT recipients were vaccinated with Pnc PS vaccine at 8 months (early group) and 21 recipients at 20 months (late group) after transplantation. Serum samples drawn before BMT, before vaccination, and at 1 and 16 months after vaccination were available from 27, 35, 34 and 30 patients, respectively. The geometric mean anti-Pnc 19F concentrations were 4.3, 1.3, 1.6 and 1.3 microg/ml in the early group and 3.8, 0.9, 0.6 and 0.6 microg/ml in the late group before transplantation, before vaccination, and at 1 and 16 months after vaccination, respectively. OPA (titre > or = 8) was found in 10/27, 5/35, 5/34 and 6/30 patients before BMT, before vaccination, and at 1 and 16 months after vaccination, respectively. The specific IgG antibody concentration and OPA correlated with each other before BMT, and in the early group patients before and at 1 month after vaccination. The results demonstrate that after Pnc PS vaccination allogeneic BMT recipients have antibodies with low functional activity to a Pnc PS antigen associated with low specific IgG responses. There is a need to study new Pnc conjugate vaccines in multi-dose schedules for their capacity to elicit higher specific antibody concentrations with high OPA in BMT recipients.

Health complaints and immunological markers of exposure to bioaerosols among biowaste collectors and compost workers

OBJECTIVESIn a cross sectional study, work related health complaints and diseases of 58 compost workers and 53 biowaste collectors were investigated and compared with 40 control subjects. Levels of specific...

IgG subclass deficiencies associated with bronchiectasis.

Only a small number of patients with IgG subclass deficiencies (IgGSD) have been observed to have bronchiectasis. Moreover, in the series of patients with bronchiectasis, IgGSD have not been found at any frequency, and the etiology of bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in 65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA test was performed to quantify subclasses 1 through 4 using subclass-specific antihuman monoclonal antibodies. IgG subclass estimation in a healthy population with age-stratified normal ranges was derived from 100 adults, 37 children aged between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum concentrations of specific IgG antibodies to Haemophilus influenzae type b capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer membrane protein complex (OMPC). Thirty-one patients (48%) had low serum concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3 deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All patients showed increased levels of total IgG, IgG1, and IgA, but this rise was significantly higher in patients without IgGSD. Patients with IgGSD showed impaired antibody response to Hib-PRP compared with patients with non-IgGSD and the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed whenever other causes of bronchiectasis have been ruled out.

Seroepidemiology of Helicobacter pylori infection in vegans and meat-eaters.

An enzyme-linked immunosorbent assay has been used to diagnose serologically the prevalence of Helicobacter pylori infection in Asian life-long vegans. There was no difference in the seropositivity between these individuals and a group of age- and sex-matched Asian meat-eaters, indicating the meat consumption is not a risk factor for H. pylori infection. However, both Asian groups had a higher prevalence of infection than age- and sex-matched Caucasian meat-eaters. Additionally, the Asian individuals had a wider range of specific IgG antibody concentrations than the Caucasians. This did not appear to be due to antigenic cross-reactivity between H. pylori and Campylobacter jejuni. The significance of these observations to the establishment of cut-off levels for the serodiagnosis of certain ethnic groups is discussed.

Pneumococcal serum antibody concentrations during the first three years of life: a study of otitis-prone and non-otitis-prone children

One hundred and thirteen children were followed prospectively from birth until the age of 3, serum being obtained from cord blood, and at the ages of 3, 6, 12, 18, 24, 30 and 36 months. Thirteen children developed recurrent acute otitis media (rAOM), 29 remained very healthy and the remaining children formed an intermediate group. Cord serum concentrations were determined of total IgG class, of IgG 1 and IgG 2 subclasses, as well as of specific IgG antibodies against the pneumococcal capsular types, 3, 6A and 19F. The specific pneumococcal IgG as well as IgA and IgM antibodies were also followed in the sequential serum samples up to the age of 3 in the rAOM and healthy children. Despite total IgG class and IgG 1 and IgG 2 subclass concentrations being of the same magnitude in cord serum of rAOM (median: 11.15, 7.48 and 2.16 g/l for IgG, IgG 1 and IgG 2, respectively) as in that of healthy children (median: 10.21, 8.16 and 2.16 g/l, respectively), both in cord serum and in most serum samples drawn during the first year of life, specific IgG antibodies against types 6A and 19F, but not against type 3, were significantly lower in the rAOM group than in the healthy children. In the intermediate group, cord serum concentrations of specific IgG antibodies to type 6A were of the same magnitude as in the healthy children. The only significant difference in specific IgM and IgA antibody concentrations against types 3, 6A and 19F between the two groups was noted for type 6A antibodies at 36 months of age where rAOM children exhibited lower values. The results indicate an association between pre-existing low specific IgG antibody levels against AOM-associated pneumococcal types and the development of rAOM.

The effect of serial intravenous immunoglobulin infusion on type-specific anti-pneumococcal antibodies in children.

The effect of a series of five immunoglobulin G infusions--at 3-4 week interval--on serum IgG antibody concentrations against some pneumococcal types commonly associated with acute otitis media (AOM) was studied in 11 children, 1-4 years old, suffering from recurrent AOM. Increase of specific IgG antibody concentrations was observed when the initial concentrations were low. However, once higher antibody concentrations had been achieved as a result of the treatment, subsequent infusions resulted in a decrease of the antibodies. In two children with initially high specific antibody concentrations, antibodies successively decreased in response to repeated immunoglobulin infusions.

Delayed hypersensitivity skin testing of 150 volunteers. Retesting results and antibody measurements.

We studied skin test reactivity to five commonly used antigens by testing 150 healthy adults. The delayed hypersensitivity (DH) skin test is widely used to assess the immune status of patients. The battery of antigens suitable for use may vary in different countries, but the reactivity to the antigens in our population did not differ remarkably from reports of other authors. The reactivity rates were: candida 32.7%, mumps 86%, streptokinase-streptodornase (SK-SD) 70%, trichophyton 0% and tuberculin 58.7%. Sixteen of the subjects were retested after 2 weeks. Only eight of them showed unchanged reactions to all five antigens. Specific IgG antibody concentrations measured by enzyme-linked immunosorbent assay (ELISA) against each of the five antigens in the serum of 42 subjects before and after testing showed great inter-individual variation. The antibody concentration did not correlate with the DH skin test results, but the testing itself increased the production of anti-mumps- and anti-SK-SD-antibodies.