Total Immunoglobulin G Levels Research Articles

Serological characteristics and clinical implications of IgG subclasses in visceral leishmaniasis.

Visceral leishmaniasis (VL) represents the most severe form of Leishmaniasis infection, often resulting in fatality without timely treatment. Previous studies have found that immunosuppression increases the risk of VL disease progression and mortality, and the total immunoglobulin G (IgG) levels in peripheral blood vary before and after treatment. However, the distinct levels and roles of IgG subclasses in VL have not been documented yet. This study aims to elucidate the characteristics and clinical significance of IgG subclasses in VL. A total of 43 cases newly-diagnosed with VL were enrolled in the cohort. We measured the levels of IgG subclasses before and after standard treatment and conducted assessments of bone marrow features. In addition, we analysed other haematological indices and examined the variations in IgG subclasses, as well as their correlation with clinical and laboratory factors. The levels of total IgG, IgG1, and the ratios of both IgG1/IgG and IgG1/IgG2 decreased significantly after treatment, whereas the ratios of IgG2/ IgG showed an obvious increase. The VL patients without hyperglobulinemia displayed significant lower IgG1/IgG2 ratios, but higher IgG2/IgG ratios compared with those with hyperglobulinemia. In addition, VL patients with positive bone marrow amastigotes had significant higher IgG1/IgG and IgG1/IgG2 ratios, but lower IgG2/IgG ratios. IgG subclasses were correlated with abnormal blood test results, particularly immunological elements including IgM and Complement 4 (C4). IgG1 and IgG2 exhibited contrasting changes after treatment in VL patients. The features of bone marrow and laboratory tests indicated that IgG1 and IgG2 serve different roles in the progression of VL. The ratios of IgG subclasses may be more precise indicators to evaluate immune reaction in VL than traditional total IgG.

How immune breakthroughs could slow disease progression and improve prognosis in COVID-19 patients: a retrospective study.

Previous infections and vaccinations have produced preexisting immunity, which differs from primary infection in the organism immune response and may lead to different disease severities and prognoses when reinfected. The purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19. A retrospective cohort study was conducted on 1513 COVID-19 patients in Chengdu Public Health Clinical Medical Center from January 2020 to November 2022. All patients were divided into the no immunity group (primary infection and unvaccinated, n=1102) and the immune breakthrough group (previous infection or vaccination, n=411). The immune breakthrough group was further divided into the natural immunity subgroup (n=73), the acquired immunity subgroup (n=322) and the mixed immunity subgroup (n=16). The differences in clinical and outcome data and T lymphocyte subsets and antibody levels between two groups or between three subgroups were compared by ANOVA, t test and chi-square test, and the relationship between T lymphocyte subsets and antibody levels and the disease progression and prognosis of COVID-19 patients was assessed by univariate analysis and logistic regression analysis. The total critical rate and the total mortality rate were 2.11% and 0.53%, respectively. The immune breakthrough rate was 27.16%. In the no immunity group, the critical rate and the mortality rate were all higher, and the coronavirus negative conversion time was longer than those in the immune breakthrough group. The differences in the critical rate and the coronavirus negative conversion time between the two groups were all statistically significant (3.72% vs. 0.24%, 14.17 vs. 11.90 days, all p<0.001). In addition, in the no immunity group, although lymphocyte counts and T subsets at admission were higher, all of them decreased consistently and significantly and were significantly lower than those in the immune breakthrough group at the same time from the first week to the fourth week after admission (all p<0.01). The total antibody levels and specific Immunoglobulin G (IgG) levels increased gradually and were always significantly lower than those in the immune breakthrough group at the same time from admission to the fourth week after admission (all p<0.001). Moreover, in the natural immunity subgroup, lymphocyte counts and T subsets at admission were the highest, and total antibody levels and specific IgG levels at admission were the lowest. Then, all of them decreased significantly and were the lowest among the three subgroups at the same time from admission to one month after admission (total antibody: from 546.07 to 158.89, IgG: from 6.00 to 3.95) (all p<0.001). Those in the mixed immunity subgroup were followed by those in the acquired immunity subgroup. While lymphocyte counts and T subsets in these two subgroups and total antibody levels (from 830.84 to 1008.21) and specific IgG levels (from 6.23 to 7.51) in the acquired immunity subgroup increased gradually, total antibody levels (from 1100.82 to 908.58) and specific IgG levels (from 7.14 to 6.58) in the mixed immunity subgroup decreased gradually. Furthermore, T lymphocyte subsets and antibody levels were negatively related to disease severity, prognosis and coronavirus negative conversion time. The total antibody, specific IgM and IgG levels showed good utility for predicting critical COVID-19 patients and dead COVID-19 patients. Among patients with COVID-19 patients, immune breakthroughs resulting from previous infection or vaccination, could decelerate disease progression and enhance prognosis by expediting host cellular and humoral immunity to accelerate virus clearance, especially in individuals who have been vaccinated and previously infected. Chinese Clinical Trial Register ChiCTR2000034563.

Mucosal humoral immune response of respiratory tract in medical workers during the post-COVID-19 period

Currently, the role of local respiratory tract immunoglobulins in COVID-19 and rearrangement of mucosal immune response in the post-COVID period have not been sufficiently studied. Our aim was to evaluate long-term effects of novel coronavirus infection on the mucosal immunity in healthcare workers over the post-infection period.&#x0D; A total of 180 healthcare workers, ranging in age from 18 to 65 years, were enrolled in a one-stage, cross-sectional study. The subjects with a history of COVID-19 were divided into three groups, depending on the severity of their disease. The control group consisted of 44 healthcare workers who had no history of novel coronavirus infection. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, naso- and oropharyngeal scrapings by ELISA technique. Specific anti-SARS-CoV-2 IgG antibodies were quantified in the serum by chemiluminescence immunoassay.&#x0D; Numerous shifts in adaptive immune response were detected for different mucosal compartments, i.e., in subjects who suffered from severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p 0.05 and p 0.005, respectively). An inverse correlation was demonstrated between the levels of total sIgA in all mucosal sites, and the number of days from the onset of disease to the start of study (r = 0.278, р 0.05). When compared to the control subjects, all the patients with prior COVID-19 had significantly higher levels of total IgG in the induced sputum samples. Total IgG in saliva was also higher in the group of patients who had severe infection (p 0.05). By contrast, IgG levels in nasopharyngeal samples were decreased in severe and moderately severe groups compared to the control group, thus, probably, indicating an immunodeficiency state in these cases. A direct significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum.&#x0D; Long-term changes in the humoral mucosal immune response were most pronounced in the healthcare workers with a history of severe or moderate-to-severe COVID-19.

Mucosal immunity in health care workers’ respiratory tracts in the post-COVID-19 period

Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome.

Dose Selection and Clinical Development of Efgartigimod PH20 Subcutaneous in Patients with Generalized Myasthenia Gravis (P1-5.017)

Dose Selection and Clinical Development of Efgartigimod PH20 Subcutaneous in Patients with Generalized Myasthenia Gravis (P1-5.017)

Serum Immunoglobulin G (IgG) Subclasses in a Cohort of Systemic Sclerosis Patients

To assess serum immunoglobulin G (IgG) subclasses in a cohort of systemic sclerosis (SSc) patients and to evaluate the influence of IgG subclasses in the main complications of the disease. The serum level of IgG subclasses was evaluated in 67 SSc patients and 48 healthy controls (HC), matched for sex and age. Serum samples were collected and measured IgG1-4 subclasses by turbidimetry. SSc patients had lower median total IgG [9.88 g/l (IQR 8.18-11.42 g/l) vs. 12.09 g/l (IQR 10.24-13.54 g/l), p < 0.001], IgG1 [5.09 g/l (IQR 4.25-6.38 g/l) vs. 6.03 g/l (IQR 5.39-7.90 g/l), p < 0.001], and IgG3 [0.59 g/l (IQR 0.40-0.77 g/l) vs. 0.80 g/l (IQR 0.46-1 g/l), p < 0.05] serum levels compared to HC. The logistic regression analysis showed IgG3 as the only variable associated with the diffusing capacity of the lung for carbon monoxide (DLco) ≤60% of the predicted [OR 9.734 (CI 95%: 1.312-72.221), p < 0.05] and modified Rodnan skin score (mRSS) [OR 1.124 (CI 95%: 1.019-1.240), p < 0.05], anti-topoisomerase I [OR 0.060 (CI 95%: 0.007-0.535), p < 0.05], and IgG3 [OR 14.062 (CI 95%: 1.352-146.229), p < 0.05] as variables associated with radiological interstitial lung disease (ILD). SSc patients have reduced levels of total IgG and an altered IgG subclass distribution compared to HC. Moreover, SSc patients show different serum IgG subclasses profiles according to the main involvement of the disease.

Efgartigimod alfa for the treatment of primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia. Most patients with ITP have antiplatelet antibodies of the immunoglobulin G (IgG) subtype which through interaction with platelet and megakaryocyte glycoproteins result in increased platelet destruction and inhibition of platelet production. There are a variety of therapeutic options available for the treatment of ITP including corticosteroids, IVIgG, TPO-RA, rituximab, fostamatinib, and splenectomy. Long-term remissions with any of these therapies can vary widely and patients may require additional therapy. The neonatal Fc receptor (FcRn) plays a pivotal role in IgG and albumin physiology through recycling pathways. Efgartigimod is a human IgG1-derived fragment that has been modified by ABDEG technology to increase its affinity for FcRn at both physiologic and acidic pH. The binding of efgartigimod to FcRn blocks the interaction of IgG with FcRn facilitating increased lysosomal degradation of IgG and decreasing total IgG levels. Based on the mechanism of action and the known pathophysiology of ITP as well as the efficacy of other therapies such as intravenous immunoglobulin (IVIG), the use of efgartigimod in patients with ITP is attractive. This article will briefly discuss the pathophysiology of ITP, current treatments, and the data available on efgartigimod in ITP.

Immunogenicity and antigenicity of a conserved fragment of the rhoptry-associated membrane antigen of Plasmodium vivax

BackgroundPlasmodium vivax rhoptry-associated membrane antigen (RAMA) is a glycophosphatidylinositol-anchored membrane protein currently under consideration as a malaria vaccine candidate. Immunoglobulin G (IgG) antibodies induced by P. vivax RAMA (PvRAMA) have been proved to persist over 12 months in the sera of people infected with P. vivax. It has also been shown that through stimulation of peripheral blood mononuclear cells with PvRAMA in vitro, the antigen can induce CD4+ T cells to produce interleukin-10. However, the genetic diversity of the RAMA gene in isolates of P. vivax (pvrama) and the immunogenicity of PvRAMA in animals remain unclear.MethodsGenomic DNA was extracted from blood samples (n = 25) of patients in Jiangsu Province, China with imported infections of P. vivax from endemic countries in South and Southeast Asia. The extract genomic DNA was used as templates to amplify the P. vivax rama gene (pvrama) by PCR, and the PCR products were then sequenced and analyzed by the DnaSP, MEGA, and GeneDoc software packages. Recombinant PvRAMA (rPvRAMA) protein was expressed and purified, and then used to immunize mice. Levels of total IgG and different IgG subclasses of rPvRAMA-immunized mice were evaluated by enzyme-linked immunosorbent assay. Also, spleen cells of rPvRAMA-immunized mice were stimulated with rPvRAMA in vitro and levels of T cells were measured by flow cytometry.ResultsThe average pairwise nucleotide diversity (π) of the pvrama gene was 0.00190, and the haplotype diversity (Hd) was 0.982. The C-terminal of PvRAMA showed lower haplotype diversity compared to the N-terminal and was completely conserved at amino acid sites related to erythrocyte binding. To further characterize immunogenicity of the C-terminal of PvRAMA, mice were immunized with rPvRAMA antigen. The rPvRAMA protein induced antibody responses, with the end-point titer ranging from 1:10,000 to 1:5,120,000. IgG1 was the predominant IgG subclass in rPvRAMA-immunized mice, followed by IgG2b. In addition, levels of CD4+ and CD8+ T cells in the rPvRAMA-stimulated group were significantly higher than those in the phosphate-buffered saline-stimulated group (normal control group).ConclusionsThe high conservation at specific amino acid sites and the high immunogenicity of the C-terminal of PvRAMA indicate the presence of conserved epitopes able to generate broadly reactive humoral and cellular immune responses. These findings support the potential of PvRAMA to serve as a vaccine candidate against P. vivax infection.Graphical

HEADACHE AS AN ADVERSE EFFECT OF IMMUNOGLOBULIN ADMINISTRATION FOR SELECTIVE IMMUNOGLOBULIN G DEFICIENCY

INTRODUCTION: IgG subclass deficiency was described by William Terry in a patient with recurrent infections. Selective IgG subclass is defined as a significant decrease in serum concentration of 1 or more IgG subclasses with normal total IgG, IgA and IgM levels. Persistent low serum levels of one or more immunoglobulin G (IgG) subclasses may be found in a high proportion of adult patients with increased susceptibility to infections (17). This deficiency has been described in association with other primary immunodeficiencies, including: selective IgA deficiency, selective IgM deficiency and Ataxia-Telangiectasia, growth hormone deficiency, Down syndrome, cystic fibrosis, among others (1). CLINICAL CASE:We present the clinical case of a 28-year-old female patient with a history of selective immunodeficiency to IgG immunoglobulin, repeated urinary tract infections, repeated vaginal infections and herpes simplex II infection, all of which have been treated, She went to a hospital in Morona Santiago three days ago for presenting, as the apparent cause, administration of immunoglobulin for a basic illness, a mild holocranial headache that evolved into a severe headache, accompanied by nausea that led to vomiting on one occasion, for which she was admitted to the hospital for pain management. Complementary examinations showed that there was no metabolic alteration or neurological deterioration, which is why she was classified as an adverse effect of the administration of immunoglobulin 3 days earlier. EVOLUTION:The patient was admitted for pain management due to severe headaches, multiple analgesics were administered without adequate response, so it was decided to start a tramadol infusion pump. During the following hours of hospitalization she remained with a feeling of nausea and weakness, however, the headache gradually subsided and it was decided to discontinue analgesic medication to assess the response of the clinical picture, and she was discharged 24 hours after admission with a favorable evolution. CONCLUSIONS: IgG subclass deficiency is a pathology characterized by the fact that it occurs in women over 16 years of age, with a very low prevalence; the presence of respiratory pathologies gives rise to the suspicion of this disease. The treatment of this pathology is based solely on the intravenous or subcutaneous administration of Immunoglobulin G, together with the concomitant treatment of the infections that the patient presents. Adverse effects should always be taken into account, as they are temporary, but quite disabling. KEYWORDS: Headache, Immunoglobulin G, Urinary Tract Infections, Herpes Simplex

Pneumococcal Conjugate Vaccine Does Not Induce Humoral Response When Administrated Within the Six Months After CD19 CAR T-Cell Therapy

CD19 targeted chimeric antigen receptor-modified T cell therapy (CAR-T) leads to B cell aplasia and low serum immunoglobulin levels. Long-lived CD19–negative plasma cells may persist through the therapy and generate antibodies. There is a paucity of data describing how CAR-T impacts the persistence of antibodies against vaccine-related antigens and the degree to which CAR-T recipients may respond to vaccines. We characterized the effect of CAR-T on pneumococcal immunoglobulin G (IgG) titers and determine whether pneumococcal conjugate vaccine (PCV13) administered after CAR-T develops long-term humoral protection against pneumococcus. A retrospective chart review was performed to identify CAR-T recipients who had serum pneumococcal IgG titers drawn before (baseline) or at days +90, +180, +270, +360, or +540 after CAR-T. We then determined whether they received PCV13 vaccination at these timepoints. IgG concentration ≥1.3 μg/mL was considered protective for that serotype, and patients with ≥6/11 tested vaccine-specific serotypes meeting this threshold were deemed to have humoral protection against pneumococcus. Absolute pneumococcal IgG titers and the proportion of patients with humoral protection, stratified by serotype, and vaccination status were compared by paired nonparametric t-tests. Absolute counts for lymphocyte, CD4 T-cell, and CD19 cell and total IgG level, along with the rate of invasive pneumococcal infections, were measured at these timepoints. A total of 148 CAR-T recipients with pneumococcal IgG titers measured for at least one of the defined time points were identified. At baseline, 25% (19/76) patients with evaluable pneumococcal IgG titers met the definition of humoral protection. Among 44 patients with paired pneumococcal IgG titers at baseline and day+90, absolute IgG titers of all serotypes decreased (geometric mean = 0.41 and 0.32 µg/mL, respectively; P < .001). Thirteen patients were vaccinated following the titer blood draw at day+90 and had paired pneumococcal IgG titers at day+90 and day180. Absolute IgG titers of all vaccine specific serotypes in these vaccinated patients decreased from day+90 to day+180 (geometric mean = 0.36 and 0.29 µg/mL, respectively; P = .03). The proportion of patients meeting the criteria of humoral protection remained the same at day+180 despite vaccination at day+90. The results were similar among 8 patients vaccinated at day+180, as well as 7 patients consecutively vaccinated at day+90 and day+180 with corresponding pneumococcal IgG titers. When all vaccine-specific pneumococcal IgG titers were pooled together by timepoint regardless of vaccination status, the proportion of patients with humoral protection decreased until day+540. Some patients developed humoral protection after vaccination at day+360, maintained seroprotective IgG titers from baseline, or developed protection after receiving intravenous immunoglobulin treatment secondary to recurrent infections. Our study demonstrated that few large B cell lymphoma patients had humoral protection against pneumococcus at baseline, and existing IgG titers decreased after CAR-T. PCV13 vaccination at day+90 or day+180 after CAR-T did not increase humoral protection against pneumococcus. Only at day+540 was there evidence of humoral protection against pneumococcus in a modest proportion of patients. Clinical trials are needed to determine the optimal timing of vaccination, before or after CAR-T, to develop protective immunity against Streptococcus pneumoniae infections.

Effect of FcRn antagonism on protective antibodies and to vaccines in IgG-mediated autoimmune diseases pemphigus and generalised myasthenia gravis

Antagonism of the neonatal Fc receptor (FcRn) by efgartigimod has been studied in several autoimmune diseases mediated by immunoglobulin G (IgG) as a therapeutic approach to remove pathogenic IgGs. Whereas reduction of pathogenic titres has demonstrated efficacy in multiple autoimmune diseases, reducing total IgG could potentially increase infection risk in patients receiving FcRn antagonists. The objective of this study was to analyse the effect of FcRn antagonism with efgartigimod on existing protective antibody titres and the ability to mount an immune response after vaccine challenge. Serum levels of total IgG and protective antibodies against tetanus toxoid (TT), varicella zoster virus (VZV), and pneumococcal capsular polysaccharide (PCP) were measured in all patients enrolled in an open-label trial of efgartigimod for the treatment of pemphigus. Vaccine specific-responses were assessed by measuring changes in IgG titres in patients with generalised myasthenia gravis (gMG) who were treated with efgartigimod and who received influenza, pneumococcal, or coronavirus disease 2019 (COVID-19) vaccines during participation in the double-blind trial ADAPT or open-label extension, ADAPT+ (n = 17). FcRn antagonism reduced levels of protective anti-TT, anti-VZV, and anti-PCP antibodies and total IgG to a similar extent; anti-TT and anti-VZV titres remained above minimally protective thresholds for the majority of patients, (10/12) 83% and (14/15) 93% respectively. Protective antibodies returned to baseline values upon treatment cessation. Antigen-specific IgG responses to influenza, pneumococcal, and COVID-19 immunisation were detected in patients with gMG who received these vaccines while undergoing therapy with efgartigimod. In conclusion, FcRn antagonism with efgartigimod did not hamper generation of IgG responses but did transiently reduce IgG titres of all specificities.

PB2305: EFGARTIGIMOD: CLINICAL DEVELOPMENT OF A NOVEL FCRN ANTAGONIST IN THE TREATMENT OF AUTOIMMUNE DISEASES

Background: Immunoglobulin G (IgG) autoantibodies play a key role in the pathogenesis of various autoimmune diseases. The neonatal Fc receptor (FcRn) is the central regulator of IgG homeostasis, rescuing IgG (including pathogenic autoantibodies) and albumin from lysosomal degradation and is responsible for the long half-life of IgG. Therapeutic blocking of FcRn leads to reduction of all IgG subtypes without reducing other immunoglobulin types, making it a possible target for symptomatic treatment of autoimmune disorders, while maintaining normal immunological responses. Efgartigimod (EFG), an FcRn antagonist, is a human IgG1-derived Fc-fragment that outcompetes endogenous IgG binding, reduces IgG recycling, and increases IgG degradation. EFG is approved in the US and Japan for treatment of generalized myasthenia gravis (MG) in adult patients. Aims: This presentation provides an overview of EFG as a molecule and summarize the clinical development program to date. Methods: Studies in healthy volunteers and patients with autoimmune diseases are already completed. Phase 3 studies in immune thrombocytopenia (ITP; ADVANCE and ADVANCE SC) and phase 2/3 studies in chronic inflammatory demyelinating polyneuropathy (ADHERE), pemphigus vulgaris and foliaceus (ADDRESS), bullous pemphigoid (BALLAD), and myositis (ALKIVIA) are ongoing. Results: In a Phase 2 trial in patients with ITP, EFG (10 mg/kg given intravenously) reduced total IgG levels by 63.7% (from mean [SD] 10.6 g/L [5.1] at baseline to 4.1 g/L [2.0]) 3 days after the fourth weekly infusion. No changes in IgG levels were observed in patients treated with placebo during that time. These reductions led to clinically relevant increases in platelet counts; 46% of EFG patients vs 25% on placebo achieved a platelet count of ≥50 x109/L on ≥2 occasions. In a Phase 3 trial in MG (ADAPT), EFG rapidly reduced IgG without impacting IgM, IgA, or albumin levels while participants recorded statistically significant functional neurological improvements. In all studies to date, EFG was well tolerated, and adverse events were mainly mild to moderate. Summary/Conclusion: FcRn inhibition by EFG is a promising potential therapeutic option for several autoimmune diseases mediated by pathogenic IgG autoantibodies.

Immunoglobulin-G subclass pattern among children with mucopolysaccharidosis attending the genetic clinic of Alexandria University Children’s Hospital

Background Mucopolysaccharidosis is an inherited lysosomal-storage disease, due to deficiency in lysosomal enzymes degrading glycosaminoglycans, causing accumulation of undegraded substrate within the lysosomes. These substrates are related to widespread inflammation, as well as the release of various proinflammatory immune mediators and autophagy dysfunction. Oxidative stress, abnormal mitochondrial function, and disruption in homeostasis also play a role in mucopolysaccharide (MPS) pathogenesis. Defects in immunological parameters in MPS have been described and postulated as explanations for the increased severity of infections seen in MPS children. Most of these infections are of the respiratory tract.Aim The aim was to estimate the total level of immunoglobulin G (IgG) and its subclasses in children with MPS and find out the relation if any between the estimated levels and the recurrence of infections.Patients and methods The study was conducted on 35 children with MPS, either newly diagnosed or previously diagnosed cases attending the genetic clinic of Alexandria University Children’s Hospital for follow-up in the period from July 2019 to July 2020. ELISA was used for estimation of the levels of total IgG and its subtypes (IgG1, IgG2, IgG3, and IgG4).Results The levels of total IgG and its subtypes (IgG1, IgG2, IgG3, and IgG4) were measured in all studied cases. A positive significant correlation between IgG3 and repeated upper respiratory-tract infections (URTIs), that 68.2% of cases with high levels of IgG3 had repeated URTIs, while only 31.8% of cases with normal levels of IgG3 had repeated URTIs with P value of 0.001.Conclusion Children with MPS are especially prone to repeated URTIs more than six times/year, this increased susceptibility to infections has been linked to abnormal parameters of the immune system. IgG subclasses are a significant predictor of recurrent URTIs in patients with MPS disease. Therefore, measurement of IgG subclass level, especially IgG3 level, provides a new strategy to more aggressive treatments for high-risk groups.

Understanding the role of serological and clinical data on assessing the dynamic of malaria transmission: a case study of Bagamoyo district, Tanzania.

naturally acquired blood-stage malaria antibodies and malaria clinical data have been reported to be useful in monitoring malaria change over time and as a marker of malaria exposure. This study assessed the total immunoglobulin G (IgG) levels to Plasmodium falciparum schizont among infants (5-17 months), estimated malaria incidence using routine health facility-based surveillance data and predicted trend relation between anti-schizont antibodies and malaria incidence in Bagamoyo. 252 serum samples were used for assessment of total IgG by enzyme-linked immunosorbent assay and results were expressed in arbitrary units (AU). 147/252 samples were collected in 2021 during a blood-stage malaria vaccine trial [ClinicalTrials.gov NCT04318002], and 105/252 were archived samples of malaria vaccine trial conducted in 2012 [ClinicalTrials.gov NCT00866619]. Malaria incidence was calculated from outpatient clinic data of malaria rapid test or blood smear positive results retrieved from District-Health-Information-Software-2 (DHIS2) between 2013 and 2020. Cross-sectional data from both studies were analysed using STATA version 14. this study demonstrated a decline in total anti-schizont IgG levels from 490.21AU in 2012 to 97.07AU in 2021 which was related to a fall in incidence from 58.25 cases/1000 person-year in 2013 to 14.28 cases/1000 person-year in 2020. We also observed a significant difference in incidence when comparing high and low malaria transmission areas and by gender. However, we did not observe differences when comparing total anti-schizont antibodies by gender and study year. total anti-schizont antibody levels appear to be an important serological marker of exposure for assessing the dynamic of malaria transmission in infants living in malaria-endemic regions.

Phase II, Multiple-Dose Study of Anti-FcRn Antibody, Rozanolixizumab (UCB7665), in Patients with Primary Immune Thrombocytopenia: Interim Analysis

Phase II, Multiple-Dose Study of Anti-FcRn Antibody, Rozanolixizumab (UCB7665), in Patients with Primary Immune Thrombocytopenia: Interim Analysis

IgG Subclass Analysis in Patients with Chagas Disease 4Years After Benznidazole Treatment.

In humans, Trypanosoma cruzi infection is controlled by a complex immune response. Immunoglobulin G (IgG) is important for opsonizing blood trypomastigotes, activating the classic complement pathway, and reducing parasitemia. The trypanocidal activity of benznidazole is recognized, but its effects on the prevention and progression of Chagas disease is not well understood OBJECTIVE: We aimed to evaluate the levels of total IgG and cross-specific IgG subclasses in patients with chronic Chagas disease of different clinical forms before and after 4years of benznidazole treatment. Eight individuals with the indeterminate form and nine with the cardiac form who completed the treatment protocol were evaluated. The levels of total IgG and IgG1, IgG2, IgG3, and IgG4 isotypes were quantified in the serum of each individual using the fluorescent immunosorbent assay. The results are expressed as relative fluorescence unit. Patients with chronic Chagas disease presented decreased levels of total IgG at 48months after benznidazole treatment. Increased IgG1 and decreased IgG3 levels were observed in patients with the cardiac form and those with exacerbated clinical forms. In addition, a decrease in the IgG3/IgG1 ratio was observed in individuals with the cardiac form of Chagas disease. Benznidazole administration in the chronic phase differentially changes IgG subclasses in patients with cardiac and indeterminate forms, and monitoring the IgG3 level may indicate the possible prognosis to the cardiac form or worsening of the already established clinical form.

Efficacy and Safety of Intravenous Efgartigimod 10 Mg/Kg in Adult Patients with Primary Immune Thrombocytopenia: Advance, a Phase 3 Clinical Trial in Progress

Efficacy and Safety of Intravenous Efgartigimod 10 Mg/Kg in Adult Patients with Primary Immune Thrombocytopenia: Advance, a Phase 3 Clinical Trial in Progress

Bariatric surgery-induced weight loss reduces B cell activating cytokines and IgG immunoglobulins related to autoimmunity.

Obesity is associated with a chronic inflammatory state and autoimmune diseases, but little is known about the role of B cells in this context and the changes in B cell activation factors during obesity and after weight loss. To test whether bariatric-surgery-induced weight loss ameliorates the systemic inflammatory state associated with B cell activation molecules. We conducted a prospective observational study in patients treated with bariatric surgery. Anthropometric and body composition measurements were performed preoperatively and at 6months of follow-up post surgery. The patients were tested for a biochemical profile, plasmatic immunoglobulin G (IgG), cytokines (including specific B cell activating cytokines), and adipokines serum levels RESULTS: The patients' weight loss was accounted for mostly by fat mass (52.9%). We observed a significant reduction in total plasmatic IgG levels (p = 0.001), which could be associated with decreased B cell activity. Accordingly, there was a significant decrease in the B cell activating factors such as APRIL, BAFF, and soluble CD40L and a general improvement in the inflammatory markers hs-CRP, IL-1β, IL-12, IL-18, and IFN-γ. These findings point toward reduced B cell activity after weight loss due to bariatric surgery. Moreover, they could be the initial link among the systemic inflammatory factors, and B cell activation in this inflammatory context that leads to IgG production and, potentially, to autoimmunity in patients with severe obesity.

Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti-C5 monoclonal antibody tesidolumab.

Awareness of drug-drug interactions is critical in organ transplant recipient management. However, biologic agents interfering with monoclonal antibodies is not widely considered. We report the effect of high-dose intravenous immunoglobulin (IVIg) on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the human anti-C5 monoclonal antibody tesidolumab (LFG316) in end-stage renal disease patients awaiting kidney transplant. In this single-center, phase 1, open-label, parallel-group study, 8 patients were assigned to receive either single-dose tesidolumab+IVIg or tesidolumab alone, with 56-day follow-up. Within-group PK parameters were consistent. Mean tesidolumab exposure decreased 34%, clearance increased 63%, and half-life decreased 41% comparing tesidolumab+IVIg to tesidolumab alone. IVIg influence on tesidolumab elimination was most evident in the first 3weeks. Complete suppression of both total and alternative complement activities was maintained for 4weeks in the tesidolumab alone group and for 2weeks in the tesidolumab+IVIg group. Tesidolumab was well tolerated. IVIg infused before tesidolumab affected tesidolumab PK and PD, resulting in a shortened period of full complement activity inhibition. These findings suggest a clinically relevant impact of IVIg on monoclonal antibody clearance and indirectly hint at an IVIg mechanism of action in treating autoimmune diseases and allosensitization by accelerating pathogenic IgG antibody degradation. Trial registration number: NCT02878616.

Cell-mediated and humoral immune profile to hydatidosis among naturally infected farm animals.

Background and Aim:Cystic echinococcosis (CE) is a widespread parasitic disease caused by Echinococcus granulosus tapeworm infect different intermediate hosts including sheep, cattle, and camels. The intermediate host’s immune response to the hydatid cyst is still conflict and complex. The current study was designed to evaluate the immune response in sera of hydatid naturally infected sheep, cattle, and camels in the form of features of inflammatory cell infiltrations, levels of Th1 and Th2 cytokines, besides the humoral specific immunoglobulin G (IgG) responses.Materials and Methods:Thirty-nine sheep, 74 cattle, and 79 camels’ sera were collected and considered as CE naturally infected and ten samples from each species were graded as non-infected. Lung specimens were collected for histopathological examination. The quantitative concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-4, and IL-10 were determined. Different antigens were prepared from hydatid cyst; hydatid cyst fluid of lung origin hydatid cyst fluid of liver origin, hydatid cyst protoscoleces of lung origin (HCP-g), hydatid cyst protoscoleces of liver origin, hydatid cyst germinal layer of lung origin, and hydatid cyst germinal layer of liver origin; and characterized by gel electrophoresis and Western blotting analysis. The total specific IgG level against E. granulosus infection was measured using an indirect enzyme-linked immunosorbent assay.Results:The results indicated that the cellular immune response in the infected tissues was characterized by inflammatory cell penetration. The pro-inflammatory Th1 cytokine profile was predominant in infected animals in comparison with non-infected ones. However, the humoral immune response was seen as a high level of IgG in infected animals. The presented data approved that the HCP-g antigen could be considered as a delegate antigen for all other prepared antigens with an immunoreactive band at molecular weights 32 kDa.Conclusion:This study provides a fundamental insight into the events that manipulate cellular and humoral immune profiles in an intermediate host; sheep, cattle, and camel that naturally infected with CE. Hence, it was concluded that CE is a constant disease and confirm the reactivity Th1 in combating hydatid cyst. Besides, it could lead to the activation of the humoral immune response in the form of a high level of IgG.