Suppression Of Antibody Production Research Articles

Neonatal SARS-CoV-2 mRNA Vaccination Efficacy Is Influenced by Maternal Antibodies.

Vaccination in pregnancy guards against infection. Maternal antibodies, however, can inhibit antibody production in neonates. We sought to determine the effects of maternal vaccination on neonatal immune response to a SARS-CoV-2 mRNA vaccine. We hypothesized that mRNA-lipid nanoparticles (LNP) vaccination allows for a de novo neonatal antibody response even in the presence of vertically transmitted maternal antibodies. Female mice were vaccinated with SARS-CoV-2 spike receptor binding domain (RBD) mRNA-LNPs. Mice were then bred, and 21-day-old pups were inoculated with the same mRNA-LNPs. Spike-specific IgG ELISAs were performed using mouse serum. A SARS-CoV-2 spike protein peptide library to perform peptide ELISAs characterized high affinity binding domains within the spike protein. Results were analyzed with one-way ANOVAs with Tukey's multiple comparisons tests. Compared to pups of unvaccinated dams, there were high levels of spike-specific IgG detected in the pups of vaccinated dams at 3 weeks of life (p < 0.0001). After neonatal vaccination, pups of unvaccinated dams had higher spike-specific serum IgG than pups of vaccinated dams at 12 weeks of life (p < 0.001). Antibody specificity to peptide moieties within spike RBD were similar when comparing a vaccinated dam to her pup at Week 3 of life, with different binding affinities observed in the pups by Week 15 of life. Pre-existing maternal antibodies may partially blunt the initial neonatal antibody response to mRNA-LNPs vaccination. This vaccine strategy, however, does not prohibit the subsequent development of a broad range of RBD antibody specificities that may be protective.

Methylprednisolone Modulates the Tfr/Tfh ratio in EAE-Induced Neuroinflammation through the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR Signalling Pathways.

Methylprednisolone (MP) is a potent glucocorticoid that can effectively inhibit immune system inflammation and brain tissue damage in Multiple sclerosis (MS) patients. T follicular helper (Tfh) cells are a subpopulation of activated CD4 + T cells, while T follicular regulatory (Tfr) cells, a novel subset of Treg cells, possess specialized abilities to suppress the Tfh-GC response and inhibit antibody production. Dysregulation of either Tfh or Tfr cells has been implicated in the pathogenesis of MS. However, the molecular mechanism underlying the anti-inflammatory effects of MP therapy on experimental autoimmune encephalomyelitis (EAE), a representative model for MS, remains unclear. This study aimed to investigate the effects of MP treatment on EAE and elucidate the possible underlying molecular mechanisms involed. We evaluated the effects of MP on disease progression, CNS inflammatory cell infiltration and myelination, microglia and astrocyte activation, as well as Tfr/Tfh ratio and related molecules/inflammatory factors in EAE mice. Additionally, Western blotting was used to assess the expression of proteins associated with the PI3K/AKT pathway. Our findings demonstrated that MP treatment ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Furthermore, it reduced microglial and astrocytic activation. MP may increase the number of Tfr cells and the levels of cytokine TGF-β1, while reducing the number of Tfh cells and the levels of cytokine IL-21, as well as regulate the imbalanced Tfr/Tfh ratio in EAE mice. The PI3K/AKT/FoxO1 and PI3K/AKT/mTOR pathways were found to be involved in EAE development. However, MP treatment inhibited their activation. MP reduced neuroinflammation in EAE by regulating the balance between Tfr/Tfh cells via inhibition of the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR signalling pathways.

Silencing of FCRLB by shRNA ameliorates MuSK-induced EAMG in mice

IntroductionMuscle specific kinase (MuSK) antibody positive myasthenia gravis (MG) often presents with a severe disease course and resistance to treatment. Treatment-refractory patients may respond to B cell depleting treatment methods. Our aim was to investigate whether inhibition of Fc receptor–like B (FCRLB) could effectively suppress autoimmunity without diminishing B cell counts in animal model of MG, a classical antibody-mediated autoimmune disease. MethodsExperimental autoimmune MG was induced in Balb/C mice with two s.c. immunizations with recombinant human MuSK in complete Freund's adjuvant. FCRLB was silenced with a lentiviral particle transported shRNA in myasthenic mice with a single i.p. injection during second MuSK-immunization. Control immunized mice received scrambled shRNA or saline. Mice were observed for clinical parameters for 28 days and at termination, anti-MuSK IgG, neuromuscular junction (NMJ) deposits, muscle AChR expression and lymph node B and T cell ratios were assessed by ELISA, immunofluorescence, immunoblotting and flow cytometry, respectively. ResultsFCRLB shRNA-treated mice showed no muscle weakness or weight loss at termination. Also, they exhibited higher grip strength and muscle AChR levels, lower anti-MuSK IgG and NMJ IgG/C3 levels than control mice. Flow cytometry analysis showed that ratios of major effector lymph node B and T cell populations were not altered by FCRLB silencing. However, regulatory T and CD19 + CD5+ B cell ratios were decreased in FCRLB shRNA-group. ConclusionOur results provide evidence regarding involvement and therapeutic value of FCRLB in MuSK-MG. Silencing of FCRLB appears to substantially inhibit antibody production without interfering with survival of major lymphocyte populations.

SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in individuals with multiple sclerosis receiving different disease-modifying treatments.

The study aims to evaluate the concentration of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike1 protein (S1RBD) in BNT162b2- vaccinated relapsing-remitting multiple sclerosis (RRMS) individuals receiving disease-modifying treatments (DMTs). Serum from 126 RRMS volunteers was collected 3 months after the administration of the second dose of the Pfizer-BioNTech BNT162b2 vaccine. Additional samples were analyzed after the administration of the booster dose in fingolimod- treated MS. Anti-S1RBD IgG antibody concentrations were quantified using the ABBOTT SARS-CoV-2 IgG II Quant assay. Anti-S1RBD IgG antibody concentrations in RRMS individuals receiving natalizumab, interferons, teriflunomide, and dimethyl fumarate showed no significant difference to those in healthy controls. However, fingolimod-treated MS individuals showed a marked inability to produce SARS-CoV-2- specific antibodies (p < 0.0001). Furthermore, a booster dose was not able to elicit the production of IgG antibodies in a large portion of matched individuals. A possible explanation for the altered immune response in fingolimod- treated MS individuals could be due to the medication inhibiting the circulation of lymphocytes, and possibly in turn inhibiting antibody production. Overall, patients on DMTs are generally of no disadvantage toward mounting an immune response against the vaccine. Nevertheless, further studies require evaluating non-humoral immunity against SARS-CoV-2 following vaccination, as well as the suitability of such vaccinations on patients treated with fingolimod.

Effectiveness and safety of COVID-19 vaccines in patients with diabetes as a factor for vaccine hesitancy.

Diabetes mellitus is one of the most common comorbid conditions encountered in patients with severe acute respiratory syndrome coronavirus 2 infection accompanied by significantly increased mortality, prolonged hospital stay, and requirement of invasive mechanical ventilation. This review aims to present the effectiveness and safety profile of available coronavirus disease 2019 (COVID-19) vaccines in people with diabetes as a potential cause of hesitancy for vaccination. Data from published research proves a robust immune response following immunization for COVID-19 in diabetic patients with substantial production of virus-neutralizing antibodies; however, the observed immune response was unequivocally weaker than that in individuals without diabetes. This observation was further enhanced by the findings that worse glycemic control was associated with more suppressed antibody production. In contrast, individuals with optimal glycemic control performed similarly to healthy controls. In addition to the need for strict glucose monitoring and adequate diabetes treatment, those findings reinforce the concept of diabetes-induced secondary immune deficiency and necessitate the application of booster doses to diabetic patients with priority. Nevertheless, after vaccination, reported adverse events were not different from those in the general population. No increase in severe adverse events was documented. While single case reports detected transient increases in blood glucose post-vaccination, more extensive trials could not replicate such a relationship.

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy.

Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which is the second or third main cause of end-stage kidney diseases in patients with primary glomerulonephritis. Substantial achievements have increased our understanding of the aetiology and pathogenesis of murine and human MN. The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition. Furthermore, additional antibody specificities for antigens have been discovered, but their pathogenic effects are uncertain. Although anti-PLA2R and anti-THSD7A antibodies as a diagnostic marker is widely used in MN patients, many questions including autoimmune response development, antigenic epitopes, and podocyte damage signalling pathways remain unresolved. This review describes the current available evidence regarding both established and novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers and DNA methylation) in MN, with an emphasis on clinical findings. This review further summarizes the applications of traditional Chinese medicines such as Tripterygium wilfordii and Astragalus membranaceus for MN treatment. Lastly, this review considers how the identification of novel antibodies/antigens and unresolved questions and future challenges reveal the pathogenesis of MN.

Probing the potential interactions between two protein vaccine candidates from Nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi) is the leading cause of AOM (acute otitis media) among children in the US, and NTHi infections contribute to the $6 billion in AOM‐related medical costs each year. NTHi is also a leading cause of COPD (Chronic Obstructive Pulmonary Disease), the third leading cause of death in adults in the US, underlining the need for a vaccine to protect us against NTHi. Two well studied protein vaccine candidates from NTHi are OMP26 and Protein D. In preliminary studies, mice produced a robust antibody response to OMP26 and Protein D when injected individually. However, when both proteins were mixed in a single solution, Protein D antibody production was significantly suppressed. We hypothesized that an interaction between the proteins prevented Protein D’s interaction with immune cells thus suppressing antibody production. Here, we discuss our biochemical approaches to study the potential OMP26‐Protein D interaction, including native mass spectrometry. Preliminary results from those studies suggest OMP26 and Protein D do not form a complex in vitro.

Evaluation of Antiasthamic Activity of Electrohomeopathy Formulation Pettorale on Experimental Animals

Objective: The current study was planned to evaluate the antiasthamatic effect of Electrohomeopathic medicine Pettorale in various experimental models.&#x0D; Methods: The antiasthmatic activity of Electrohomeopathic medicine Pettorale was studied on different experimental animals like histamine induced bronchospasm in guinea pig, haloperidol induced catalepsy in rats, egg albumin induced paw anaphylaxis in rats and milk induced leukocytosis in mice.&#x0D; Conclusion: Preliminary phytochemical screening has revealed the presence of alkaloids, glycosides, carbohydrates, amino acids, proteins, steroids and terpenoids. Petorella exhibited best antihistaminic activity at the dose of 400 mg/kg. It inhibited haloperidol-induced catalepsy, increased leukocyte count and increased eosinophil count due to milk allergen. Antiasthmatic activity of Pettorale may be possible due to the membrane stabilising potential, suppression of antibody production and inhibition of antigen induced histamine release.&#x0D; Keywords: Electrohomeopathy, Pettorale, catalepsy, asthma, histamine

Incorporating Gangliosides into PEGylated Cationic Liposomes that Complexed DNA Attenuates Anti-PEG Antibody Production but Not Anti-DNA Antibody Production in Mice.

Gangliosides (glycosphingolipids) reduce antibody production by inhibiting B-cell receptor (BCR) signaling. We have shown that a copresentation of gangliosides and polyethylene glycol (PEG) on the same liposomes suppresses anti-PEG IgM production in mice. In addition, we recently observed that pDNA incorporated in PEGylated cationic liposomes (PCLs) induces anti-DNA IgM, which could be a hurdle to the development of efficient gene delivery systems. Therefore, the focus of this study was to determine if the copresentation of gangliosides and DNA on the same PCL would suppress antibody production against DNA. PCLs including DNA induced both anti-PEG IgM production and anti-DNA IgM production. The extent of anti-PEG and anti-DNA IgM production was likely dependent on the immunogenicity of the complexed DNA. Treatment of clodronate-containing liposomes, which causes a depletion of phagocytic cells, suppressed anti-PEG IgM production from PCLs that did not include DNA but failed to suppress anti-PEG IgM production from PCLs that complexed DNA (PCLD). Both anti-PEG IgM and anti-DNA IgM was induced in T-cell-deficient nude mice as well as in normal mice following treatment with PCLs and PCLD, respectively. These results indicate that phagocytic cells contribute to anti-PEG IgM production but not to anti-DNA IgM production, while T-cells do not contribute to any form of antibody production. The copresentation of gangliosides and DNA significantly reduced anti-PEG IgM production but unfortunately did not reduce anti-DNA IgM production. It appears that the immunosuppressive effect of gangliosides, presumably via the CD22 signaling pathway, is limited only to anti-PEG immunity.

IL-21 Receptor Blockade Shifts the Follicular T Cell Balance and Reduces De Novo Donor-Specific Antibody Generation.

Donor-specific antibodies (DSAs) play a key role in chronic kidney allograft injury. Follicular T helper (Tfh) cells trigger the humoral alloimmune response and promote DSA generation, while T-follicular regulatory (Tfr) cells inhibit antibody production by suppressing Tfh and B cells. Interleukin (IL)-21 exerts a distinct effect on Tfh and Tfr. Here, we studied whether blocking IL-21R with anti-IL-21R monoclonal antibody (αIL-21R) changes the Tfh/Tfr balance and inhibits DSA generation. First, we investigated the impact of αIL-21R on CD4+ T cell proliferation and apoptosis. The results showed that αIL-21R did not have cytotoxic effects on CD4+ T cells. Next, we examined Tfh and regulatory T cells (Tregs) in an in vitro conditioned culture model. Naïve CD4+ T cells were isolated from 3-month-old C57BL/6 mice and cultured in Tfh differentiation inducing conditions in presence of αIL-21R or isotype IgG and differentiation was evaluated by CXCR5 expression, a key Tfh marker. αIL-21R significantly inhibited Tfh differentiation. In contrast, under Treg differentiation conditions, FOXP3 expression was inhibited by IL-21. Notably, αIL-21R rescued IL-21-inhibited Treg differentiation. For in vivo investigation, a fully mismatched skin transplantation model was utilized to trigger the humoral alloimmune response. Consistently, flow cytometry revealed a reduced Tfh/Tfr ratio in recipients treated with αIL-21R. Germinal center response was evaluated by flow cytometry and lectin histochemistry. We observed that αIL-21R significantly inhibited germinal center reaction. Most importantly, DSA levels after transplantation were significantly inhibited by αIL-21R at different time points. In summary, our results demonstrate that αIL-21R shifts the Tfh/Tfr balance toward DSA inhibition. Therefore, αIL-21R may be a useful therapeutic agent to prevent chronic antibody mediated rejection after organ transplantation.

Dysregulatory processes of the cellular link of the immune system in the dynamics of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a variant of primary immunodeficiency in which inhibition of antibody production is formed due to disorders of intercellular interaction affecting cellular elements of both innate and adaptive immune responses. A feature of CVID is the late start and variability of clinical minifestation. These arguments determine the purpose of the study: to identify the dynamics of changes in the cellular parameters of the adaptive and innate immune response depending on the duration and severity of the infectious manifestation of CVID. In this regard, a retrospective analysis of medical histories and dynamic observation of fifteen patients with CVID were carried out. Selection of specific parameters of cellular indices of factors of innate resistance and adaptive immunity was carried out on the basis of systemic-functional approach of immunodiagnostics. It is shown that in patients with CVID -mediated hypogammaglobulinemia and infectious phenotype of clinical manifestation, enhancement of quantitative and functional potentials of T-link effector cells of adaptive immunity is recorded against the background of reduction of number of regulatory T-helpers. With a more severe clinical course of the disease, the number of CD3+HLA DR + limphocytes is lower than with a more favorable version, there is a tendency to decrease the number of these cells, as well as the number of peripheral Treg with an increase in the length of the disease. Cellular components of innate immunity are characterized by a decrease in neutrophil activity, inhibition of antigen-presenting monocyte activity, the number and cytotoxicity of natural killers. At the same time, the tendency to decrease the cytolytic potential of NK with an increase in the length of illness and statistically significant differences depending on the severity of the manifestation of the infectious phenotype of CVID was recorded. The obtained results determine the importance of evaluating the cellular link of the immune system in patients with CVID, including as a prognostic criterion for the severity of the course.

Immunoglobulins and Transcription Factors in Otitis Media.

The causes of otitis media (OM) involve bacterial and viral infection, anatomo-physiological abnormalities of the Eustachian canal and nasopharynx, allergic rhinitis, group childcare centers, second-hand smoking, obesity, immaturity and defects of the immune system, formula feeding, sex, race, and age. OM is accompanied by complex and diverse interactions among bacteria, viruses, inflammatory cells, immune cells, and epithelial cells. The present study summarizes the antibodies that contribute to immune reactions in all types of otitis media, including acute otitis media, otitis media with effusion, and chronic otitis media with or without cholesteatoma, as well as the transcription factors that induce the production of these antibodies. The types and distribution of B cells; the functions of B cells, especially in otorhinolaryngology; antibody formation in patients with otitis media; and antibodies and related transcription factors are described. B cells have important functions in host defenses, including antigen recognition, antigen presentation, antibody production, and immunomodulation. The phenotypes of B cells in the ear, nose, and throat, especially in patients with otitis media, were shown to be CD5low, CD23high, CD43low, B220high, sIgMlow, sIgDhigh, Mac-1low, CD80(B7.1)low, CD86(B7.2)low, and Syndecam-1low. Of the five major classes of immunoglobulins produced by B cells, three (IgG, IgA, and IgM) are mainly involved in otitis media. Serum concentrations of IgG, IgA, and IgM are lower in patients with OM with effusion (OME) than in subjects without otitis media. Moreover, IgG, IgA, and IgM concentrations in the middle ear cavity are increased during immune responses in patients with otitis media. B cell leukemia/lymphoma-6 (Bcl-6) and paired box gene 5 (Pax-5) suppress antibody production, whereas B lymphocyte inducer of maturation program 1 (Blimp-1) and X-box binding protein 1 (XBP-1) promote antibody production during immune responses in patients with otitis media.

Cigarette Smoke Exposure Inhibits Early Phase of Antibody Production through Inhibition of Immune Functions in Alveolar Macrophage

Background::Cigarette smoke (CS) is inhaled into the lung. Alveolar macrophage (AM) is known to play an important role in the lung immune system. However, the relationship between AM functions and antibody production by CS is not fully investigated.Objective::Therefore, we investigated the effects of AM from CS exposed mice on antibody production. Mice were exposed to 20 cigarettes/day for 10 days. AM were obtained by broncho-alveolar lavage. Antibody production was analyzed by plaque-forming cell assay using seep red blood cell (SRBC) as antigen.Methods::B cell proliferation was analyzed by 3H-thymidine incorporation. Phagocytic activity using fluorescein isothiocyanate-labeled SRBC and expressions of surface antigens on AM were analyzed by flow cytometry. Cytokines and NF-κB mRNA expressions of AM were analyzed by RTPCR.Results and Discussion:Antibody production was decreased at the induction phase, but not at the expression phase by AM from smoked mice (SM) compared with non-smoked mice (NSM). B cell proliferation was decreased by cigarette extracts dose-dependently. Phagocytic activity of AM was decreased in SM compared with NSM. Expression of surface antigens on AM was decreased in SM compared with NSM. Cytokines or NF-κB mRNA expressions of AM were decreased in SM compared with NSM.Conclusion::These results suggest that the inhibition of antibody production by cigarette smoking is caused by the inhibition of phagocytosis and expressions of surface antigens associated with antigen presentation. Such inhibition of AM functions may increase the risk of bacterial and virus infections.

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

Cigarette smoke exposure inhibit antibody production via inhibition of alveolar macrophage

Cigarette smoke exposure inhibit antibody production via inhibition of alveolar macrophage

A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides

Guillain-Barré syndrome (GBS), including its variant Miller Fisher syndrome (MFS), is an acute peripheral neuropathy that involves autoimmune mechanisms leading to the production of autoantibodies to gangliosides; sialic acid-containing glycosphingolipids. Although association with various genetic polymorphisms in the major histocompatibility complex (MHC) is shown in other autoimmune diseases, GBS is an exception, showing no such link. No significant association was found by genome wide association studies, suggesting that GBS is not associated with common variants. To address the involvement of rare variants in GBS, we analyzed Siglec-10, a sialic acid-recognizing inhibitory receptor expressed on B cells. Here we demonstrate that two rare variants encoding R47Q and A108V substitutions in the ligand-binding domain are significantly accumulated in patients with GBS. Because of strong linkage disequilibrium, there was no patient carrying only one of them. Recombinant Siglec-10 protein containing R47Q but not A108V shows impaired binding to gangliosides. Homology modeling revealed that the R47Q substitution causes marked alteration in the ligand-binding site. Thus, GBS is associated with a rare variant of the SIGLEC10 gene that impairs ligand binding of Siglec-10. Because Siglec-10 regulates antibody production to sialylated antigens, our finding suggests that Siglec-10 regulates development of GBS by suppressing antibody production to gangliosides, with defects in its function predisposing to disease.

Gender Disaggregation in COVID-19 and Increased Male Susceptibility.

Novel coronavirus disease 2019 (COVID-19) is a growing public health crisis. Despite initial focus on the elderly population with comorbidities, it seems that large studies from the worst affected countries follow a sex-disaggregation pattern. Analysis of available data showed marked variations in reported cases between males and females among different countries with higher mortality in males. At this early stage of the pandemic, medical datasets at the individual level are not available; therefore, it is challenging to conclude how different factors have impacted COVID-19 susceptibility. Thus, in the absence of patients' level data, we attempted to provide a theoretical description of how other determinants have affected COVID-19 susceptibility in males compared to females. In this article, we have identified and discussed possible biological and behavioral factors that could be responsible for the increased male susceptibility. Biological factors include - an absence of X-chromosomes (a powerhouse for immune-related genes), a high level of testosterone that inhibits antibody production, and the presence of Angiotensin-converting enzyme 2 (ACE2) receptors that facilitate viral replication. Similarly, behavioral factors constitute - higher smoking and alcohol consumptions, low level of handwashing practices, and high-risk behavior like non-adherence to health services and reluctance to follow public health measures in males. Keywords: COVID-19; gender; males; sex disaggregation; susceptibility.

Does Celiac Disease Affect Antibody Production Against Hepatitis B in Children?

Background: Celiac disease is an immune-mediated systemic disease, in which gluten ingestion causes different symptoms. HLA-DQ2 is positive in 90% - 95% of celiac patients. HLA has been considered to inhibit antibody production against the hepatitis B virus vaccine. Considering that celiac disease affects about 1% of the population, this phenomenon could be a significant factor in immunization programs. On the other hand, HLA-DQ2 positive patients not only are at the risk of HBV infection themselves but also have the potential to be an important source of HBV dissemination in the world. Objectives: This study was carried out to evaluate the responsiveness of celiac-affected children to HBV vaccination in Iran. Methods: This case-control prospective study was performed on 62 Iranian children (31 children with confirmed celiac disease before introducing a gluten-free diet and 31 healthy children). HBS Ab (antibody against hepatitis B virus surface antigen) titer was checked in the patients and compared between the two groups. Results: It was shown that 67.7% of cases and 64.5% of controls had HBS Ab titer above 10 mIU/mL, but the difference was not significant statistically. After matching for the time interval from the last HBV vaccination, it was observed that although non-significantly, celiac disease can decrease the chance for anti-HBS production up to 30%. Conclusions: This study did not confirm non-responsiveness against the HBV vaccine in celiac disease in children. This may be due to genetic factors or type of vaccine. Moreover, in our study, responsiveness was assessed qualitatively in the two groups (HBS Ab &gt; 10 mIU/mL was considered as a responder).

Effects of Monoacyltrehalose Fraction of Rhodococcus Biosurfactant on the Innate and Adaptive Immunity Parameters In Vivo.

The biosurfactant monoacyltrehalose fraction isolated from Rhodococcus ruber IEGM 231 actinobacterium suppresses antibody production, bactericidal potential, and production of IL-1β by mouse peritoneal cells after intraperitoneal and intramuscular injection and stimulates the production of IL-10 after intraperitoneal injection. The data of in vitro experiments attest to an important role of bacterial glycolipids in the regulation of the functions of splenocytes and peritoneal macrophages.

Effects of AS2819899, a novel selective PI3Kδ inhibitor, in a NZB/W F1 mouse lupus-like nephritis model

Phosphoinositide 3-kinases generate lipid-based second messengers that control an array of intracellular signaling pathways. In particular, phosphoinositide 3-kinases delta (PI3Kδ) is expressed primarily in hematopoietic cells and plays an important role in B-cell development and function. B cells play a critical role in autoimmune diseases by producing autoantibodies. Studies have therefore increasingly focused on PI3Kδ as a therapeutic target for the treatment of inflammatory and autoimmune diseases. One such autoimmune disease is systemic lupus erythematosus (SLE). SLE is a chronic systemic autoimmune disease with repeated recurrence and remission, and autoantibodies play an important role in its pathogenesis. Here, we examined the pharmacological profile of the novel PI3Kδ selective inhibitor AS2819899 and investigated its therapeutic potential against SLE in a NZB/W F1 mouse lupus-like nephritis model, a widely-used SLE mouse model. AS2819899 prevented B and T cell activation in vitro, and inhibited antibody production in a T-cell independent de novo antibody production mouse model. In the spontaneous NZB/W F1 mouse model, AS2819899 treatment significantly reduced anti-dsDNA antibody titers and improved kidney dysfunction. Further, AS2819899 inhibited the memory recall reaction in a T-cell dependent antibody production mouse model, suggesting that AS2819899 can potentially maintain remission of SLE. Moreover, we identified a pharmacodynamics marker for AS2819899 that may be useful in clinical studies. These results indicate that AS2819899 may be an attractive therapeutic candidate for SLE, including the maintenance of remission.