IgD Levels Research Articles

Altered B-cell, plasma cell and antibody immune profiles in blood of systemic mastocytosis

Systemic mastocytosis (SM) is a heterogeneous disease characterised by an expansion of KIT-mutated constitutively activated mast cells (MC) which release MC mediators that might act on the tumour microenvironment including other immune cells. Here we investigated the blood distribution of B-cell, plasma cell (PC) and antibody-isotype compartments in SM. We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B-cells, PC and their subsets in blood of 108 SM patients - 35 bone marrow mastocytosis (BMM), 64 indolent SM (ISM), 9 aggressive SM (ASM)- vs 117 age-matched healthy donors (HD) and paired bone marrow (BM) samples of 31 SM vs 17 controls, respectively. In parallel, immunoglobulin (Ig) M, IgD, IgG, IgA and IgE plasma levels of were measured. Compared to HD, SM patients showed an increased immature B-cell production in BM (P=0.003) associated with a greater release of pre-germinal center immature (P<0.001) and naive CD5+ B-lymphocytes (P<0.001) to blood, but a pronounced decrease in PC counts of all different IgH-isotypes and subclasses (P≤0.001) together with overall increased IgM (P=0.001) and IgD (P<0.001) plasma levels. Of note, different immune profiles were found per diagnostic subtype of the disease with progressively greater counts in blood of immature B-lymphocytes together with decreased IgMD+, IgG2+, IgA1+ and IgA2+ MBC (P≤0.032) and elevated IgM (P=0.017) plasma levels in ASM cases, increased IgM (P=0.001) and IgD (P=0.001) plasma levels in ISM patients and exacerbated IgE (P<0.001) with decreased IgG (P=0.008) plasma levels in BMM cases. Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.

Causality of genetically proxied immunophenotypes on cardiovascular diseases: a Mendelian randomization study.

Cardiovascular diseases (CVDs) stand as the foremost global cause of mortality, prompting a growing interest in using the potential of immune cells for heart injury treatment. This study aims to assess the causal association between immune cells and CVDs. A total of 731 immune cells were derived from a previously published genome-wide association study (GWAS), which included approximately 22 million genetic variants among 3,757 individuals of Sardinian ancestry. Genetic associations with atrial fibrillation (AF), heart failure, coronary artery disease, myocardial infarction and stroke were extracted from large-scale GWAS. A two-sample Mendelian randomization (MR) analysis was used to assess the causal association between immune cells and CVDs. Replication MR analysis based on FinnGen dataset and meta-analysis are sequentially conducted to validate causal relationships. Collectively, genetically predicted 4 immune cell traits were associated with AF and 5 immune cell traits were associated with stroke. Increased levels of IgD- CD38dim absolute count were associated with a higher susceptibility to AF, while increased expression of CD14+ CD16+ monocytes, CD62L on CD62L+ myeloid dendritic cells, and CD16 on CD14- CD16+ monocytes were linked to a decreased susceptibility to AF. Additionally, an elevated susceptibility to stroke was linked to an increase in the percentage of CD39+ resting Tregs and heightened CD27 expression on IgD- CD38+ cells. Conversely, a decreased susceptibility to stroke was associated with increased CD40 expression on monocytes, particularly on CD14+ CD16+ and CD14+ CD16- monocytes, with the latter two showing the most compelling evidence. This study identified several immune cell traits that have a causal relationship with CVDs, thus confirming that immune cells play an important role in the pathogenesis of these diseases.

Single-cell RNA sequencing reveals diverse B cell phenotypes in patients with anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by prominent psychiatric symptoms. Although the role of NMDAR antibodies in the disease has been extensively studied, the phenotype of B cell subsets is still not fully understood. We utilized single-cell RNA sequencing, single-cell B cell receptor sequencing (scBCR-seq), bulk BCR sequencing, flow cytometry, and enzyme-linked immunosorbent assay to analyze samples from both NMDAR-E patients and control individuals. The cerebrospinal fluid (CSF) of NMDAR-E patients showed significantly increased B cell counts, predominantly memory B (Bm) cells. CSF Bm cells in NMDAR-E patients exhibited upregulated expression of differential expression genes (DEGs) associated with immune regulatory function (TNFRSF13B and ITGB1), whereas peripheral B cells upregulated DEGs related to antigen presentation. Additionally, NMDAR-E patients displayed higher levels of IgD- CD27- double negative (DN) cells and DN3 cells in peripheral blood (PB). In vitro, DN1 cell subsets from NMDAR-E patients differentiated into DN2 and DN3 cells, while CD27+ and/or IgD+ B cells (non-DN) differentiated into antibody-secreting cells (ASCs) and DN cells. NR1-IgG antibodies were found in B cell culture supernatants from patients. Differential expression of B cell IGHV genes in CSF and PB of NMDAR-E patients suggests potential antigen class switching. B cell subpopulations in the CSF and PB of NMDAR-E patients exhibit distinct compositions and transcriptomic features. In vitro, non-DN cells from NMDAR-E can differentiate into DN cells and ASCs, potentially producing NR1-IgG antibodies. Further research is necessary to investigate the potential contribution of DN cell subpopulations to NR1-IgG antibody production.

Internet gaming disorder and aggression: A meta-analysis of teenagers and young adults.

Internet gaming disorder (IGD) and aggression (AG) are widespread phenomena around the world. Numerous studies have explored the relationship between the two but findings from such studies are inconsistent. The meta-analysis aimed to evaluate the relationship between IGD and AG as well as identify the variables moderating the relationship. Studies investigating the relationship between IGD and AG were searched using selected terms to identify studies published from 1999 to 2022 on CNKI, Wanfang Data, Chongqing VIP Information Co., Ltd. (VIP), Baidu scholar, ProQuest dissertations, Taylor & Francis, Springer, Web of Science, Google Scholar, Elsevier Science (Science Direct), EBSCO, and PsycINFO. The identified studies were pooled and analyzed. A total of 30 samples comprising 20,790 subjects were identified. Results showed that there was a moderate relationship between IGD and AG (r = 0.300, 95%CI [0.246, 0.353]). Moderator analysis revealed that the relationship between IGD and AG was moderated by the region, age, and survey year. This meta-analysis indicated that people with a higher level of IGD might show more aggression, and people with more aggression might have a higher level of IGD. The correlation coefficient between IGD and AG was significantly higher in Asia than in Europe, higher in primary school than in middle school and university, and higher by increasing year. Overall, our findings provide a basis for developing prevention and intervention strategies against IGD and AG. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375267, 42022375267.

In Search of Clinical Markers: Indicators of Exposure in Dampness and Mold Hypersensitivity Syndrome (DMHS)

Potential markers were sought to diagnose mold hypersensitivity. Indoor air condensed water and human macrophage THP-1 test were applied to evaluate the buildings. Basophil activation tests (BAT) were conducted and mold-specific immunoglobulins (IgE, IgG, IgA, and IgD) were measured in study subjects' serum and feces. Exposed subjects reported markedly more symptoms from occupational air than controls. Basophils from exposed subjects died/lost activity at 225 times lower concentrations of toxic extracts from the target building than recommended in the common BAT protocol. Fecal IgG and IgD levels against Acrostalagmus luteoalbus and Aspergillus versicolor produced receiver operating curves (ROC) of 0.928 and 0.916, respectively, when plotted against the inflammation marker MRP8/14. Assaying serum immunoglobulin concentrations against the toxic Chaetomium globosum (MTAV35) from another building, a test control, did not differentiate study individuals. However, if liver metabolism produced the same core molecule from other Chaetomium globosum strains, this would explain the increased response in fecal immunoglobulins in the exposed. The altered immunoglobulin values in the samples of exposed when compared to controls revealed the route of mold exposure. The toxicity of indoor air condensed water samples, BAT and serology confirmed the severity of symptoms in the target building's employees, supporting earlier findings of toxicity in this building.

Research on differences and influencing factors of inclusive green development in Beijing-Tianjin-Hebei region

Abstract Inclusive green development (IGD), adhering to harmonious between human and nature, is a sustainable approach pursuing economic growth, social equity, achievement sharing and ecological environment. This study takes the Beijing-Tianjin-Hebei (BTH) region as an example. After systematically sorting out the connotation of IGD, more comprehensive resource and environmental indicators are added to build an evaluation system. The entropy weight and material flow analysis method are used to study the time series characteristics of the level of IGD in BTH from 1992 to 2021, and the differences and the influencing factors among the three places are analyzed by the Theil index. The results show that: (1) The level of IGD in BTH showed a steady upward trend. (2) The Theil index curve of BTH has undergone an inverted "U"-shaped change, and has initially reached regional coordination in recent years. (3) Issues of social life as well as resource and environment, having surpassed economic issues, become main causes of differences in BTH. (4) The gaps in indicators such as industrial structure and scale, social security, information and technology popularization, natural resources, and ecological restoration ability fluctuate greatly. The gaps in population development, information popularization and environmental governance are decreasing rapidly, while industrial structure, urbanization and natural resources are increasing rapidly, deserving more concentration. Keywords: Inclusive green development, Beijing-Tianjin-Hebei coordination, Entropy weight method, Theil index, Obstacle analysis, Regional differences analysis.

IgD/FcδR is involved in T-cell acute lymphoblastic leukemia and regulated by IgD-Fc-Ig fusion protein

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients’ blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment.

Levels of immunoglobulin isotypes in serum and respiratory samples of patients with chronic obstructive pulmonary disease: protocol for a systematic review and meta-analysis

IntroductionChronic obstructive pulmonary disease (COPD) is an inflammatory respiratory disorder characterised by the progressive worsening of lung function. Acute exacerbation of COPD (AECOPD) is a leading contributor to patient morbidity,...

Immune-dysregulation in subacute sclerosing panencephalitis: An exploratory case-control study.

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case-control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells, and cytotoxic T-cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy.

Proteomics Investigation of Diverse Serological Patterns in COVID-19

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Primary Immune Dysregulation in Subacute Sclerosing Panencephalitis: A Case-Control Study

Objective The primary objective was to study the pattern of immune dysregulation in cases with subacute sclerosing panencephalitis (SSPE). The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months, Background SSPE is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. Design/Methods This was a prospective observational study conducted at a tertiary-case referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Results Patients with SSPE had a mean age of 14.76 years (± 6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells and cytotoxic T-cells were significantly higher in cases. IgG, IgM and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). No correlation of immunological parameters with outcome was found. Conclusions Significant immune dysregulation in terms of lymphocyte subsets and immunoglobulin levels seem to exist in SSPE. These findings may pave way for targeted immunomodulator therapy that can be targeted in a larger cohort of patients.

IgD Multiple Myeloma, Does It Still Have a Poor Prognosis?

IgD Multiple myeloma is considered unusual myeloma, with just 2% of cases of MM being diagnosed as IgD subtype. The infrequency of its presentation and the poor prognosis make the disease challenging to treat, with many patients being selected for clinical trials. A 63-year-old female presented to the ER after falling on ice. After undergoing a CT Head, multiple lytic lesions in the occipital region were found, confirmed by MRI. 2 months later, a bone marrow biopsy found 90% of marrow replaced by CD138 plasma cells, positive for kappa & negative for lambda, consistent with myeloma. On evaluation, she was found to have pan-hypo-gammglobulinemia. However, the skeletal survey did not find any other lytic lesions. Seeing this, IgD levels were measured and found to be >100 times over the upper normal limit with normal beta2-microglobulin levels, confirming monoclonal gammopathy. A FISH study found the patient positive for t(11;14)/CCND1IGH translocation (85% of cells) and negative for TP53. Palliative radiotherapy for the skull base was performed before the patient started chemotherapy. The patient was deemed a suitable candidate, selected for a clinical trial, and placed on RVd [revlimid + velcade + dexamethasone] with delayed bone marrow transplant. As the patient developed a rash and neuropathy from velcade [bortezomib], it was paused and restarted after three months. The patient was doing well on this chemotherapy regimen for two years and was placed on lenalidomide-based maintenance therapy. Two years later, her disease started progressing with an increased frequency of bone pains and opioid dosing. At this juncture, it was decided to change course and start her on pomalidomide/dexamethasone. This did not help the patient, and the neurological side effects of dexamethasone made us change course and initiate a daratumumab, bortezomib, cyclophosphamide and dexamethasone. This proved unfruitful, too, as the patient developed adverse effects of polyneuropathy, pancytopenia requiring transfusion, and worsening GERD. Seeing the disease relapse and intolerance to the previous regimen, we decided to initiate a once-per-week regimen of selinexor, bortezomib, and dexamethasone. The patient has improved on this regimen and is back to her baseline for physical activity, mental status and pain, and an improved appetite. In this case, we wanted to highlight how incidental findings on a CT lead us to diagnose a rare type of multiple myeloma and how, in the era of novel agents, the survival of patients can be prolonged significantly. Considering the rarity of this subtype, international collaborative studies are suggested to further elucidate the underlying mechanisms for developing potent therapeutic approaches. Most of the data reported on how IgD multiple myeloma progresses was written before the arrival of novel agents. More evaluation of survival times and progression of the disease needs to be done as it's possible that IgD MM is not as poor a prognosis as it once was.

Mevalonate kinase gene polymorphisms in ankylosing spondylitis patients: A cross-sectional study.

This study aimed to investigate the potential effect of the mevalonate kinase (MVK) gene polymorphisms on the pathogenesis and clinical findings in ankylosing spondylitis (AS) patients. This cross-sectional study was conducted with 103 participants (63 males, 40 females) between January 2013 and January 2014. Of these, 51 (32 males, 19 females; mean age: 37.3±10.2 years; range, 19 to 60 years) were adult AS patients who met the 1984 Modified New York Criteria, and 52 (31 males, 21 females; mean age: 33.8±12 years; range, 19 to 60 years) were healthy volunteers with similar demographics. MVK gene analysis was performed using polymerase chain reaction sequencing by isolating deoxyribonucleic acids from peripheral blood samples. We determined serum immunoglobulin (Ig)D levels using radial immunodiffusion. We performed physical examinations on the AS patients. The Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index forms were filled and erythrocyte sedimentation rate, C-reactive protein, and IgD levels were recorded. There was no statistically significant difference in the mean age between the groups (p=0.121). The frequency of symptomatic single nucleotide polymorphisms (SNPs), c.769-38 C>T heterozygous, c.769-7 T>G heterozygous, and c.769-38 C>T homozygous were similar between the groups (15/15; p=0.646). Nonsymptomatic SNPs were more common in the patient group, but the difference was not significant (83/58; p>0.05). The rate of having an MVK gene polymorphism was 36 (70.6%) in the AS compared to the 33 (63.4%) in the control group (p>0.05). There were no associations in clinical findings between the AS patients with or without MVK gene polymorphisms. New heterozygous SNPs, I56V A>G, E281D G>D, V80I G>A, and C173Y G>A, were present in four AS patients. The frequency of MVK gene polymorphisms was higher in AS patients than in healthy controls. But there was no statistically significant difference. We determined no effect of the present polymorphisms on AS clinical and laboratory findings.

Immunopathology of SARS-CoV-2 Infection: A Focus on T Regulatory and B Cell Responses in Children Compared with Adults.

While the clinical impact of COVID-19 on adults has been massive, the majority of children develop pauci-symptomatic or even asymptomatic infection and only a minority of the latter develop a fatal outcome. The reasons of such differences are not yet established. We examined cytokines in sera and Th and B cell subpopulations in peripheral blood mononuclear cells (PBMC) from 40 children (<18 years old), evaluating the impact of COVID-19 infection during the pandemic’s first waves. We correlated our results with clinical symptoms and compared them to samples obtained from 16 infected adults and 7 healthy controls. While IL6 levels were lower in SARS-CoV-2+ children as compared to adult patients, the expression of other pro-inflammatory cytokines such as IFNγ and TNFα directly correlated with early age infection and symptoms. Th and B cell subsets were modified during pediatric infection differently with respect to adult patients and controls and within the pediatric group based on age. Low levels of IgD− CD27+ memory B cells correlated with absent/mild symptoms. On the contrary, high levels of FoxP3+/CD25high T-Regs associated with a moderate–severe clinical course in the childhood. These T and B cells subsets did not associate with severity in infected adults, with children showing a predominant expansion of immature B lymphocytes and natural regulatory T cells. This study shows differences in immunopathology of SARS-CoV-2 infection in children compared with adults. Moreover, these data could provide information that can drive vaccination endpoints for children.

Immunogenicity of a germline-targeting nanoparticle in knock-in mice expressing human B cell receptors of the HIV gp41 neutralizing antibody, DH511

Abstract The Membrane Proximal External Region (MPER) of HIV Envelope represents a key target for vaccine development due to high neutralization breadth and potency of MPER-specific broadly neutralizing antibodies (bnAbs). However, neutralizing antibody responses to MPER epitopes are restricted by tolerance control and the MPER epitope is absent from many HIV immunogens under clinical investigation. Using computational design and yeast display, a candidate germline-targeting (GT5) immunogen was developed that bound strongly to the inferred human unmutated common ancestor (UCA) of the distal MPER bnAb DH511, as well as to several human DH511-like potential precursor antibodies. We studied the immunogenicity of a multimeric nanoparticle of the GT5 immunogen in a knock-in mouse line expressing human DH511.UCA B cell receptors (BCRs). Naïve DH511.UCA knock-in mice exhibited a reduction in overall B cell numbers, and DH511.UCA-bearing B cells expressed low levels of surface IgM and IgD, suggesting that DH511.UCA expression is subject to immune tolerance control. Nonetheless, following immunization with GT5 nanoparticles mixed with a saponin/monophosphoryl lipid A adjuvant, knock-in mice mounted robust anti-GT5 humoral responses, including anti-GT5 IgG in serum and GT5-specific germinal center B cells and T follicular helper cells in lymphoid tissues. Sequencing analysis of IgG+ GT5-specific B cells revealed improbable mutations in knock-in immunoglobulin genes of DH511.UCA. These studies will guide further optimization of immunogens with potential to select for development of bnAbs against MPER epitopes. Supported by a grant from NIH (P01-AI138211)

γδ Tcells license immature B cells to produce a broad range of polyreactive antibodies.

Immature autoreactive B cells are present in all healthy individuals, but it is unclear which signals are required for their maturation into antibody-producing cells. Inducible depletion of γδ Tcells show that direct interaction between γδ Tcells and immature B cells in the spleen support an "innate" transition to mature B cells with a broad range of antigen specificities. IL-4 production of γδ Tcells and cell-to-cell contact via CD30L support B cell maturation and induce genes of the unfolded protein response and mTORC1 signaling. Eight days after invivo depletion of γδ Tcells, increased numbers of B cells are already stuck in the transitional phase and express increased levels of IgD and CD21. Absence of γδ Tcells leads also to reduced levels of serum anti-nuclear autoantibodies, making γδ Tcells an attractive target to treat autoimmunity.

Pre-treatment of Nile tilapia (Oreochromis niloticus) with ozone nanobubbles improve efficacy of heat-killed Streptococcus agalactiae immersion vaccine

Nanobubble technology has shown appealing technical benefits and potential applications in aquaculture. We recently found that treatment with ozone nanobubbles (NB–O3) activated expression of several immune-related genes leading to effective response to subsequent exposure to fish pathogens. In this study, we investigated whether pre-treatment of Nile tilapia (Oreochromis niloticus) with NB-O3 can enhance specific immune responses and improve efficacy of immersion vaccination against Streptococcus agalactiae. Spleen and head kidney of fish in the vaccinated groups showed a substantial upregulation in expression levels of pro-inflammatory cytokine genes (IL-1β, TNF-α, IL-6) and immunoglobulin classes (IgM, IgD, IgT) compared with the unvaccinated control groups. The mRNA transcript of pro-inflammatory cytokine genes was greatest (approx. 2.8–3.3 folds) on day 7 post-vaccination, whereas the relative expression of immunoglobulin genes was greatest (approx. 3.2–4.1 folds) on day 21 post-immunization. Both systemic and mucosal IgM antibodies were elicited in vaccinated groups. As the result, the cumulative survival rate of the vaccinated groups was found to be higher than that of the unvaccinated groups, with a relative percent survival (RPS) ranging from 52.9 to 70.5%. However, fish in the vaccinated groups that received pre-treatment with NB-O3, bacterial antigen uptakes, expression levels of IL-1β, TNF-α, IL-6,IgM, IgD, and IgT, as well as the specific-IgM antibody levels and percent survival, were all slightly or significantly higher than that of the vaccinated group without pre-treatment with NB-O3. Taken together, our findings suggest that utilizing pre-treatment with NB-O3 may improve the immune response and efficacy of immersion vaccination in Nile tilapia.

Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation.

Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch.

Prevalence of primary immunodeficiency syndromes in tuberculous meningitis: A case-control study

BackgroundOnly a proportion of patients with tuberculosis develop tuberculous meningitis. We hypothesize that inherent abnormalities in the host’s innate or adaptive immune system may affect the outcome in tuberculous meningitis. In this study, we evaluated the proportion of underlying primary immunodeficiency in patients with tuberculous meningitis and its impact on the outcome. MethodsNewly-diagnosed cases with tuberculous meningitis and healthy controls were included. Patients with HIV disease were excluded. Blood specimen were subjected to immunological assessment to detect primary immunodeficiency syndrome/s. We estimated serum levels of IgG, IgA, IgM, IgE and IgD along with complement C3, C4, and C5 assay. Absolute lymphocyte count was obtained from an automated three-part cell counter. Flow cytometry was used to enumerate the following lymphocyte subsets: T Cell (CD3, CD4, CD8), B cell (CD19/CD20), and Natural killer cells (CD16 and CD56). Cases were followed for 6 months. Modified Barthel Index was used as a measure of disability. ResultsWe included 55 cases with tuberculous meningitis and 30 healthy controls. We notedthat among immune parameters, absolute lymphocyte count and CD4 T-cell count in the tuberculous meningitis group was lower; higher serum IgG levels were noted in the poor outcome group. On multivariate regression analysis, none of the immunological, clinical or radiological features were found to predict a poor outcome. ConclusionHost’s immune factors contribute to the pathogenesis of tuberculous meningitis. Absolute lymphocyte count and CD4+ T-cell count were lower in tuberculous meningitis cases. Higher serum IgG levels may be associated with a poor outcome. A study with a larger sample size is needed to confirm our findings.

P084 Recurrent fever in children: why not a mevalonate kinase deficiency?

Abstract Background Mevalonate kinase deficiency (MKD) is a rare autosomal recessive auto inflammatory disease. The clinical spectrum of this disease is a continuum ranging from the moderate form of Hyper-IgD syndrome (HIDS) to lethal forms of mevalonic aciduria (MA). An autoinflammatory disease should be considered in children with recurrent fever of unexplained origin. Case report M, 28 months old boy from a non-consanguineous marriage of Algerian parents, presented since the age of two months’ episodes of unexplained fever resistant to antibiotics and requiring several hospitalizations. Family history found that the mother and a maternal uncle experienced an unexplained recurrent fever. Personal history found episodes of fever lasting in average 6 days, with no obvious cause and recurring every 15–20 days; associated with bilateral cervical adenopathy, mouth ulcers, arthralgia, abdominal pain with vomiting and diarrhea. Clinical examination confirmed the fever with temperature of 38.7°, Chills and irritability, Multiple cervical adenopathy oral aphthae, tongue of geographical aspect, cervical pain and large joint arthralgia, tender abdomen with no organomegaly. Biologic workups found major inflammatory syndrome with hyper leucocytosis at 14X103/mm3 predominantly polynuclear, high CRP level, high ESR at 110 mm. Blood cultures and viral serologies were negative. Immunoelectrophoresis found elevated IgA, IgG and IgM with a normal IgD level. Chest X-ray and abdominal ultrasound were normal. The diagnosis of MKD in its moderate form was supported by elevated urinary mevalonic acid excretion to 5.1 mmol/mol during the febrile episode and subsequently confirmed by a 2nd contributory urine assay during another febrile episode. Conclusion MKD is a rare disease. The clinical spectrum of this condition is variable and could benefit of an effective treatment. Our patient developed a moderate form with a better long-term prognosis.