IgG Ab Research Articles

Is the combination of two automated rapid assays for diagnosis of heparin-induced thrombocytopenia necessary?

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.

Immune Response to SARS-CoV-2 in Vaccine-naive Pregnant Women: Assessment of IgG and IgA Antibody Profile at Delivery and 42 Days Postpartum.

This prospective cohort study assessed the SARS-CoV-2 IgG and IgA Ab profiles at delivery and 42 d postpartum in unvaccinated SARS-CoV-2-positive pregnant women and determined the association with the timing and the clinical course of the infection. A total of 387 vaccine-naive women with confirmed SARS-CoV-2 infection during pregnancy were included. IgG and IgA Abs were detected in maternal blood at delivery and 42 d postpartum using ELISA kits. The relationships between Ab detection and value and clinical features, including the timing of the infection, were analyzed using univariate and multivariate logistic and linear regression models. The mean gestational age at infection was 31 4/7 wk of pregnancy. Symptoms of SARS-CoV-2 infection were present in 88.1% of women. IgG and IgA Abs were detected in 45.7 and 58.9% at delivery, respectively, increasing to 72.7 and 76.8% at 42 d postpartum. Detection of IgG and IgA Abs in maternal blood at delivery was independently associated with symptomatic infection (adjusted odds ratio [OR] 3.13, 95% confidence interval (CI): 1.47-6.69 and adjusted OR 3.62, 95% CI: 1.8-7.26, respectively), but not with the time from positive swab to delivery or gestational age at positive swab. Detection of Abs at 42 d postpartum was also strongly associated with the detection of Abs at delivery (OR 29.97, 95% CI: 10.11-88.82 for IgG and OR 13.09, 95% CI: 6.37-26.9 for IgA). Vaccine-naive pregnant women exhibit a significant and durable immune response to SARS-CoV-2, which is more pronounced in symptomatic women but independent of gestational age at diagnosis or the diagnosis-to-delivery interval.

Prevalence of occult hepatitis C virus infection (OCI) among hemodialysis patients; a cross-sectional study from Lorestan Province, Western Iran.

Patients with chronic kidney disorders, such as hemodialysis, are at a higher risk of infection with hepatitis viruses than the other population due to high nosocomial transmission by the dialysis units. The incidence of occult HCV infection (OCI) among chronic hemodialysis (CHD) remains controversial and the real burden of HCV in this population may be affected by the rate of OCI. This study aimed to evaluate the prevalence of OCI among patients with CHD from Lorestan province, Western Iran. In this cross-sectional study, whole blood samples were collected from 122 patients with CHD. Subsequently, anti-HCV antibody and HCV-RNA were assessed in serum/peripheral blood mononuclear cells (PBMCs) using Enzyme-Linked Immunosorbent Assay and Real-Time PCR technique, respectively. Out of the 122 patients, 61.15% were male and 38.8% were female. Regarding HCV results, out of the 122 studied patients, 4 cases (3.3%) were positive for anti-HCV IgM Ab and 3 patients (2.47%) for anti-HCV IgG Ab in their serum. Moreover, none of the 122 patients were positive for HCV-RNA in serum samples, while in PBMC samples, two patients (1.6%) tested positive for HCV-RNA, of which one patient was anti-HCV IgG Ab positive. Furthermore, the prevalence of OCI was correlated with the history of blood transfusion and serum level of transaminases (P = 0.012). The results of the current study suggest that there is a potential risk of occult HCV infection among patients undergoing hemodialysis. Therefore, it is necessary to use appropriate molecular techniques for early diagnosis and treatment of these patients.

Evaluation of a Novel Detection Method for Allergen-Specific IgE Antibodies with IgE Receptor Crosslinking Using Rat Food Allergy Model.

The specific detection of serum IgE antibodies specific to allergens (sIgE Abs) that can crosslink the plural high-affinity IgE receptor (FcεRIα) molecules on the surface of mast cells or basophils with a multivalent allergen can reduce the false-positive diagnoses observed in chemiluminescent and fluorescence enzyme immunoassays for type-I allergic patients. In this study, we detected sIgE Abs to the egg-allergen ovalbumin (OVA) and the wheat-allergen gluten in the sera of rats sensitized with each allergen using an amplified luminescence proximity homogeneous assay by crosslinking (AlphaCL). OVA and gluten were reacted with each sIgE Ab in the sera. Then, acceptor and donor beads labeled with the human FcεRIα were added to the reacted solution. The luminescence intensity for anti-OVA IgE Abs in the sera with the removal of IgG Abs was observed in five of seven (71.4%) of the sensitized rats, whereas no signals were observed in any of the unsensitized rats. The AlphaCL could also detect anti-gluten sIgE Abs in the sera of sensitized rats, but not of unsensitized rats. In conclusion, we successfully detected sIgE Abs in the sera of rats sensitized to two allergens using the AlphaCL. This detection method has the potential to be used as a new diagnostic tool for type-I allergic patients.

Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.

Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment. We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs. Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19. The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.

Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy.

Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization. Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed. Choroid sprouts treated with 30µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

New-onset diabetes in children during the COVID-19 Pandemic: an assessment of biomarkers and psychosocial risk factors at play in Mississippi.

The coronavirus disease 2019 (COVID-19) pandemic has led to an association between COVID-19 and pediatric diabetes. Studies have indicated the increased likelihood of children with COVID-19 infection developing diabetes. Our objective was to assess not only the increase in pediatric diabetes at our hospital and identify possible risk factors, but also to correlate the psychosocial changes resulting from the pandemic with new-onset diabetes. We analyzed data from 58 children aged 1 to 18 years admitted to our hospital with new-onset diabetes between March 2020 and December 2021. The data included inflammatory biomarkers and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (Abs), as well as the results of a lifestyle questionnaire. The average number of hospital admissions per month for new-onset diabetes increased from 10 to 18 with the start of the pandemic. Of the 58 children in our analysis, 33% had positive SARS-CoV-2 IgG Ab, 31% had type 1 diabetes mellitus, and 62% had type 2 diabetes mellitus (T2DM). More than half (54%) were experiencing diabetic ketoacidosis. Those with T2DM were older, majority African American, had higher median body mass index (BMI) percentiles, and lower vitamin D levels. There were no significant correlations between any psychosocial risk factors and either diabetes type or SARS-CoV2 Ab status. Despite the increased incidence of new-onset diabetes among children in Mississippi during the pandemic, this study was unable to demonstrate a significant correlation between COVID-19 infection and new-onset diabetes. The findings of this study highlighted the correlation between increased BMI and type 2 diabetes, underscoring the significant problems of obesity and diabetes in our study region. Further research is warranted.

Engineering Dimeric EGFR-directed IgA Antibodies Reveals a Central Role of CD147 during Neutrophil-mediated Tumor Cell Killing of Head and Neck Squamous Cancer Cells.

Human IgA Abs engage neutrophils for cancer immunotherapy more effectively than IgG Abs. Previous studies demonstrated that engineering approaches improved biochemical and functional properties. In this study, we report a novel, to our knowledge, IgA2 Ab against the epidermal growth factor receptor generated by protein engineering and polymerization. The resulting molecule demonstrated a covalent linkage of L and H chains and an effective polymerization by the joining chain. The engineered dimer outperformed its monomeric variant in functional experiments on Fab-mediated modes of action and binding to the Fc receptor. The capacity to engage neutrophils for Ab-dependent cell-mediated cytotoxicity (ADCC) of adherent growing target cancer cells was cell line dependent. Although the engineered dimer displayed a long-term efficacy against the vulva carcinoma cell line A431, there was a notable in-efficacy against human papillomavirus (HPV)- head and neck squamous cell carcinoma (HNSCC) cell lines. However, the highly engineered IgA Abs triggered a neutrophil-mediated cytotoxicity against HPV+ HNSCC cell lines. Short-term ADCC efficacy correlated with the target cells' epidermal growth factor receptor expression and the ability of cancer cell-conditioned media to enhance the CD147 surface level on neutrophils. Notably, the HPV+ HNSCC cell lines demonstrated a significant increment in releasing soluble CD147 and a reduced induction of membranous CD147 on neutrophils compared with HPV- cells. Although membranous CD147 on neutrophils may impair proper IgA-Fc receptor binding, soluble CD147 enhanced the IgA-neutrophil-mediated ADCC in a dose-dependent manner. Thus, engineering IgA Abs and impedance-based ADCC assays provided valuable information regarding the target-effector cell interaction and identified CD147 as a putative critical parameter for neutrophil-mediated cytotoxicity.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. We identified 166 patients with neurological symptoms appearing in less than 1month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1year follow-up. One patient died, and 15% of patients relapsed. Age > 70years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12months. No predictors of relapse were identified. This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Dissecting signaling parameters in autoreactive B cells

Abstract In systemic lupus erythematosus (SLE), IgG antibodies (Abs) directed against nuclear antigens (ANA) are pathogenic. Healthy individuals (HC) harbor a similar frequency of ANA+ mature B cells without producing pathogenic IgG Abs. Differences in behavior between ANA+/- B cells in SLE patients and HC have not been explored. The aim of this study was to measure the response to BCR activation in the ANA+/- B cell subpopulations in SLE patients and HC. B cells from 7 SLE patients and 5 HC were isolated and activated with F(ab)'2 fragments of anti-IgG Abs. Calcium flux was measured using indo-1 AM. The response was quantified by area under the curve (AUC), using the bound/unbound ratio of the marker for 5 minutes after activation. Values were compared using Wilcoxon rank sum test. In SLE patients, ANA+ IgG memory cells have a stronger calcium influx than ANA- (AUC for ANA + vs -: 89.46±18.51 vs 76.17±12.65; p=0.05). This difference is not present in HC (AUC for ANA + vs -: 88.02±16.51 vs 89.52±14.49; p=ns). In both HC and SLE patients, ANA+ naïve B cells are less responsive to BCR activation, suggesting anergy. IgM+ B cells overall, irrespective of ANA status, seem to be less responsive in patients with SLE. These results show that ANA+ IgG memory B cells are hyperreactive in SLE patients. The data also suggests a mechanism for the breach in tolerance that is observed in SLE. Further studies are warranted to explore the mechanism and effects on autoantibody generation in SLE.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Antigenic markers of T. gondii for chronic forms of toxoplasmosis in fertility age women

Objective: This study aimed to assess the avidity of IgG antibodies against Toxoplasma gondii in fertile-aged women with a history of abortion. Using the recomLine Toxoplasma IgG Avidity kit, the research investigated the relationship between antibody avidity, T. gondii antigens (GRA1 and SAG1), and the number of abortions to enhance understanding of infection dynamics in this population.
 Methods : Forty (40)fertile aged women (18-37years) with history of abortion and had positive results of IgG Abs by minividus form October 2021 to April 2022 ,Kit of recomLine Toxoplasma IgG Avidity form Mikrogen /Germany,item No.11010, was used ,which is a qualitative in vitro test for the determination the avidity of IgG antibodies against Toxoplasma gondii in human serum or plasma.
 Results: Phase II of toxoplasmosis was positive of antibodies against different antigens detected by recomLine assay, no other significant relation was observed. Also, that there was no significant relation between the period of infection and avidity of IgG –Abs against different antigens of T.gondii detected by recomLine test. In addition The results showed that there was a significant relation between of the number of abortions to GRA1-antigen (P=0.012) and SAG1-antigen (P=0.003) .
 Conclusion: There was a significant relation between of the number of abortions to GRA1 and SAG1-antigens detected by recomLine assay ,where increase in the positive results with the increase in the number of abortions.

Prolonged SARS-CoV-2 T Cell Responses in a Vaccinated COVID-19-Naive Population.

Exploring T cell response duration is pivotal for understanding immune protection evolution in natural SARS-CoV-2 infections. The objective of the present study was to analyze the T cell immune response over time in individuals who were both vaccinated and COVID-19-naive and had undetectable levels of SARS-CoV-2 IgG antibodies at the time of testing. We performed a retrospective descriptive analysis using data extracted from the electronic medical records of consecutive adult individuals who underwent COVID-19 immunity screening at a private healthcare center from September 2021 to September 2022. The study participants were divided into three groups according to the post-vaccination time period, as follows: group A (up to 3 months), group B (3-6 months), and group C (>6 months). T cell response was evaluated using the IGRA methodology T-SPOT®.COVID. Of the total number of subjects (n = 165), 60/165 (36.4%) had been vaccinated in the last 3 months (group A), 57/165 (34.5%) between 3 and 6 months (group B), and 48/165 (29.1%) at least 6 months prior to the examination day (group C). T cell positivity was reported in 33/60 (55.0%) of group A, 45/57 (78.9%) of group B, and 36/48 (75%) of group C (p < 0.007). No statistically significant differences were revealed in the spot-forming cell (SFC) count among groups, with mean SFC counts of 75.96 for group A, 89.92 for group B, and 83.58 for group C (Kruskal-Wallis test, p = 0.278). Our findings suggest that cellular immunity following SARS-CoV-2 vaccination may endure for at least six months, even in the presence of declining or absent IgG antibody levels.

Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.

IL-15 Complex-Induced IL-10 Enhances Plasmodium-specific CD4+ T Follicular Helper Differentiation and Antibody Production.

Malaria, which results from infection with Plasmodium parasites, remains a major public health problem. Although humans do not develop long-lived, sterilizing immunity, protection against symptomatic disease develops after repeated exposure to Plasmodium parasites and correlates with the acquisition of humoral immunity. Despite the established role Abs play in protection from malaria disease, dysregulated inflammation is thought to contribute to the suboptimal immune response to Plasmodium infection. Plasmodium berghei ANKA (PbA) infection results in a fatal severe malaria disease in mice. We previously demonstrated that treatment of mice with IL-15 complex (IL-15C; IL-15 bound to an IL-15Rα-Fc fusion protein) induces IL-10 expression in NK cells, which protects mice from PbA-induced death. Using a novel MHC class II tetramer to identify PbA-specific CD4+ T cells, in this study we demonstrate that IL-15C treatment enhances T follicular helper (Tfh) differentiation and modulates cytokine production by CD4+ T cells. Moreover, genetic deletion of NK cell-derived IL-10 or IL-10R expression on T cells prevents IL-15C-induced Tfh differentiation. Additionally, IL-15C treatment results in increased anti-PbA IgG Ab levels and improves survival following reinfection. Overall, these data demonstrate that IL-15C treatment, via its induction of IL-10 from NK cells, modulates the dysregulated inflammation during Plasmodium infection to promote Tfh differentiation and Ab generation, correlating with improved survival from reinfection. These findings will facilitate improved control of malaria infection and protection from disease by informing therapeutic strategies and vaccine design.

The impact of ABO blood types on humoral immunity responses and antibody persistency after different COVID-19 vaccine regimens.

This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022. Anti-Spike IgG and neutralizing Ab rise were tracked on Day 21 as well as the humoral immune persistency assessment 180 after booster shots. Late adverse events up to 6 months after the booster dose were collected. The results showed that blood type A, led to a significantly higher anti-Spike Ab rise in AstraZeneca primed recipients in comparison with Sinopharm primed ones in heterologous regimens (p: 0.019). Furthermore, blood type O was a great co-effector in homologous AstraZeneca recipients regarding neutralizing Ab rise (0.013). In addition, blood type O led to a better anti-Spike Ab persistency in the Sinopharm homologous group whereas type A had the best effect on neutralizing Ab durability in the same vaccine group. What is more, Rh-positive individuals in AstraZeneca + PastoCovac Plus group had a higher rate of anti-Spike Ab rise (p = 0.001). Neutralizing Ab rise was also induced in AstraZeneca homologous and heterologous regimens of Rh-positive individuals significantly higher than Sinopharm primed cases. The present study showed the potential impact of blood types A/O and Rh-positive on a better humoral immune responses and Ab persistency. It is proposed that blood type A and Rh-positive could increase the Ab rise in AstraZeneca vaccinated individuals. Moreover, blood type O might be a better co-effector of anti-Spike Ab persistency in Sinopharm recipients.

Seroprevalence and risk factors of Toxoplasma gondii infection among pregnant women.

Toxoplasma gondii is an obligate intracellular parasite affecting a broad range of warm-blooded animals, including humans. Infection acquired during pregnancy can be transmitted to the fetus and leading to serious problems such as spontaneous abortion, stillbirth, or severe mental and/or physical handicaps in the child. The purpose of this study was to investigate the seroprevalence of Toxoplasma infection and related risk factors in pregnant woman. The study enrolled 1200 serum samples of pregnant women from February-November 2017. Then the samples were tested for the presence of anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. Out of the 1200 samples, 381 (31.7%) and 41 (3.4%) subjects were positive for IgG and IgM Ab, respectively. Among the evaluated risk factors, the seroprevalence of Toxoplasma infection was not related to the occupation in a significant way. However significant relationship was observed with factors such as; contact with soil, cats, consumption of raw washed vegetables, and washed hands before meals. According to the results, more than two-thirds of pregnant women are susceptible to Toxoplasma infection, hence training health care programs should be provided to prevent infection.

IgG antibody response to SARS-CoV-2 infection and its influencing factors in lymphoma patients

BackgroundThe ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients.Patients & methods80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods.ResultsThe anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1–5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels.ConclusionsHumoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients.

Antibody Response to the Sneathia vaginalis Cytopathogenic Toxin A during Pregnancy.

Sneathia vaginalis is a Gram-negative vaginal species that is associated with pregnancy complications. It produces cytopathogenic toxin A (CptA), a pore-forming toxin. To determine whether CptA is expressed invivo and to examine the mucosal Ab response to the toxin, we examined human midvaginal swab samples obtained during pregnancy for IgM, IgA, and IgG Abs with CptA affinity. This subcohort study included samples from 93 pregnant people. S. vaginalis relative abundance was available through 16S rRNA survey. There were 22 samples from pregnancies that resulted in preterm birth in which S. vaginalis relative abundance was <0.005%, 22 samples from pregnancies that resulted in preterm birth with S. vaginalis ≥0.005%, 24 samples from pregnancies that resulted in term birth with S. vaginalis <0.005%, and 25 samples from pregnancies that resulted in term birth with S. vaginalis ≥0.005%. IgM, IgA, and IgG with affinity for CptA were assessed by ELISA. The capacity for the samples to neutralize CptA was quantified by hemolysis assay. All three Ab isotypes were detectable within different subsets of the samples. There was no significant association between relative abundance of S. vaginalis and the presence of any Ab isotype. The majority of vaginal swab samples containing detectable levels of anti-CptA Abs neutralized the hemolytic activity of CptA, with the strongest correlation between IgA and neutralizing activity. These results demonstrate that S. vaginalis produces CptA invivo and that CptA is recognized by the host immune defenses, resulting in the production of Abs with toxin-neutralizing ability.