Methyl-supplemented nutrition delays the development of autoimmune disease in pristane-induced murine lupus.

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl-containing micronutrients with possible anti-inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.

Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells.

The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.

Effect of Autoimmune Cell Therapy on Immune Cell Content in Patients with COPD: A Randomized Controlled Trial.

OBJECTIVE: To explore the effect of autoimmune cell therapy on immune cells in patients with chronic obstructive pulmonary disease (COPD) and to provide a reference for clinical treatment of COPD. METHODS: Sixty patients with stable COPD were randomly divided into control group and treatment group (n = 30). The control group was given conventional treatment, and the treatment group was given one autoimmune cell therapy on the basis of conventional treatment. The serum levels of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the peripheral blood were detected by flow cytometry. Possible adverse reactions were detected at any time during treatment. RESULTS: There were no significant differences in the contents of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the serum of the control group (P > 0.05). Compared with before treatment, the contents of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the serum of the treatment group were significantly increased (P < 0.05). The ratio of CD4 + /CD8+ T cells in both control and treatment groups did not change significantly during treatment (P > 0.05). There were no significant differences in serum CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the treatment group at 30 days and 90 days after treatment (P > 0.05), but they were significantly higher than those in the control group (P < 0.05). CONCLUSION: Autoimmune cell therapy can significantly increase the level of immune cells in the body and can be maintained for a long period of time, which has certain clinical benefits for recurrent respiratory tract infections and acute exacerbation in patients with COPD.

The immunomodulatory effect of koumine on B cells under dependent and independent responses by T cells.

Dysregulated activation of polyclonal B cells and production of pathogenic antibodies are involved in the development of rheumatoid arthritis (RA). Therefore, targeted B cell therapy is effective against RA. Gelsemium elegans (Gardn. & Champ.) Benth., a toxic plant widely distributed in Southeast Asia, has been used for treating rheumatoid pain, neuropathic pain, spasticity, skin ulcers, and cancers for many years in traditional Chinese medicine. Koumine, an alkaloid monomer from Gelsemium elegans Benth., exerts therapeutic effects against RA. However, whether koumine affects B cells remains unknown. In this study, the effect of koumine on B cells under T cell-independent (TI) and T cell-dependent (TD) immune responses is investigated in vitro and in vivo. Mouse primary B cells were obtained by immunomagnetic bead sorting, and immunomodulatory effects of koumine on the activation, proliferation, and differentiation of B cells were determined in TI and TD models induced by lipopolysaccharide (LPS) and anti-CD40 antibodies in vitro, respectively. The humoral immune responses of TI and TD were established using NP-AECM-FICOLL and NP-CGG in C57BL/6J mice, respectively. We found that koumine inhibited B cell differentiation in the TI model and inhibited B cell activation and proliferation in the TD model in vitro. Koumine also inhibited antibody secretion in TI immune response, TD initial immune response, and in TD secondary immune response. Our results reveal that koumine has a direct and indirect immune regulatory effect on B cells, showing that it can directly inhibit the differentiation and secretion of autoantibodies after abnormal activation of B cells, and indirectly inhibit the activation and proliferation of TD B cells to reduce the secretion of antibodies. It may be an important mechanism for its anti-RA effect in mice, providing a rationale and laboratory data support for the application of koumine in anti-human RA therapy.

Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma.

PURPOSE: CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies. METHODS: We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies. RESULTS: Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody-drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis.

Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity.

Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.

New developments in Sjogren's syndrome.

SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely empirical and offer only symptomatic relief for patients. There are no proven treatments that alter disease progression or treat the systemic manifestations of disease. B-cell depletion is used in patients with systemic disease but its overall clinical efficacy has not been demonstrated in two large randomized controlled trials. Studies are now focussing on alternative strategies to target B-cells, including co-stimulation targets, with promising data. It is increasingly clear that clinical trials in SS will require patient stratification and relevant and sensitive outcome measures to identify successful treatment modalities.

Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the immune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in the expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFß; p = 0.049), whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFß in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

Colloidal Manganese Salt Improves the Efficacy of Rabies Vaccines in Mice, Cats, and Dogs.

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model.

Effects of Vitamin D and Dexamethasone on Lymphocyte Proportions and Their Associations With Serum Concentrations of 25-Hydroxyvitamin D3In Vitro in Patients With Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder.

Background: Clear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate. Objective and Methods: Patients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D3 (serum 25(OH)D3) were explored. The impact of 1,25(OH)2D3 stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated. Results: In both MS and NMOSD, stimulation of PBMCs with 1,25(OH)2D3 followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19+CD27+ memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)2D3 was negatively correlated with serum 25(OH)D3 in MS (Spearman's ρ=-0.594, p=0.042), but positively correlated in NMOSD (Pearson's r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19+CD24+CD38+ regulatory B cells and serum 25(OH)D3 in either MS or NMOSD. In addition, the level of 1,25(OH)2D3-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D3 (for ΔCT, r=0.744, p=0.014) in MS. Conclusion: These findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D3 and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.

Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity.

Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood.

Cells of the skin and circulation are in constant two-way communication. Following exposure of humans to sunlight or to phototherapy, there are alterations in the number, phenotype and function of circulating blood cells. In this review, only data obtained from human studies are considered, with changes induced by UV radiation (UVR) exposure described for phagocytic leukocytes and peripheral blood mononuclear cells plus their component T and B cells, natural killer cells and dendritic cells. These immune modulations illustrate the potential of UVR to have therapeutic effects beyond the skin, and that sunlight exposure is an important environmental influence on human health.

Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis.

Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.

Distribution difference of colostrum-derived B and T cells subsets in gilts and sows.

Piglets are highly vulnerable to infections, but colostrum provides them with some protection. The function of colostrum components is unknown, as is if the amount and subsets of leukocytes in colostrum differ between gilts and sows. This study serially characterized leukocyte populations in colostrum for differential leukocyte counts. Differences in humoral and cellular composition of colostrum between 40 gilts and 40 sows (parities orders 3-4) from a commercial herd were examined. Flow cytometry is a useful tool to identify and quantify leukocyte subsets in sow colostrum. Overall, there were no (p ≥ 0.05) parity differences in total macrophages, granulocytes, and T and B cells. However, the sows' colostrum presented significantly higher (p ≤ 0.05) T lymphocyte subsets than gilts, such as central memory CD4+T cells, effector memory CD4+T cells, and central memory CD8+T cells. Among B-lymphocytes, percentages of SWC7+CD5+ cells were significantly higher in sow colostrum than in that of gilts. As expected, IgG concentrations were significantly higher in sows than in gilts. Colostrum from sows had significantly greater mitogenic activity than colostrum from gilts and this fact can be associated with the potential to accelerate the maturation of a newborn's gastrointestinal tract. Our findings suggest that parity order may be one among other factors influencing the cell population and, consequently, the immune adaptive response in piglets that induces neutralizing antibodies and cellular immune responses to antigens.

A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans.

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy.

INTRODUCTION: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). OBJECTIVE: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. METHODS: Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. RESULTS: At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. CONCLUSIONS: The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.

The basic immunology of asthma.

In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the disease such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbations. However, only half the asthmatics have this "type 2-high" signature, and "type 2-low" asthma is more associated with obesity, presence of neutrophils, and unresponsiveness to corticosteroids, the mainstay asthma therapy. Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated in clinical studies targeting specific immune pathways.

The effects of all-trans retinoic acid on immune cells and its formulation design for vaccines.

As one of the most important metabolites of vitamin A, all-trans retinoic acid (RA) plays a crucial role in regulating immune responses. RA has been shown to promote the differentiation of naïve T and B cells and perform diverse functions in the presence of different cytokines. RA also induces gut tropic lymphocytes through upregulating the expression of chemokine (C-C motif) receptor 9 (CCR9) and α4ß7 integrin. In addition, RA promotes the expression of the enzyme retinal dehydrogenase (RALDH) on dendritic cells, which in turn strengthens the ability to synthesize RA. Due to the insolubility of RA, proper formulation design can maximize its ability to improve immune responses for vaccines. Recent studies have developed some formulations co-loading RA and antigen, which can effectively imprint lymphocytes gut homing properties and induce intestine immune responses as well as systemic responses through parenteral administration, providing a promising direction for the protection against mucosal infections. Here, we review the mechanism and effects of RA on lymphocyte differentiation and gut homing, and recent progress of RA delivery systems to improve mucosal immune responses.

Relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and patient immunity after 6 month hospital discharge.

OBJECTIVES: To investigate the relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and immunity alteration for patients after 6-month hospital discharge. METHODS: One IgM(+) and IgG(-), 32 IgM(+) and IgG(+), 38 IgM(-) and IgG(+), and 40 IgM(-) and IgG(-) patients were included. Demographic data were collected. IgM and IgG antibodies, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and lymphocyte subsets in serum were determined at weeks 0, 2 and 4. RESULTS: The hs-CRP and IL-6 levels of all patients were within the normal ranges. The number of patients with all lymphocyte subset testing items within normal ranges was 12/110 (10.9%) at week 0, 15/110 (13.6%) at week 2 and 18/110 (16.4%) at week 4. The percentages of CD8 + cells, NK cells and B lymphocytes in the IgM(+) and IgG(+) group were quite different from those in the IgM(-) and IgG(+) group and the IgM(-) and IgG(-) group, with much higher percentages of CD8 + cells and much lower percentages of NK cells and B lymphocytes at weeks 0, 2 and 4. Twelve IgM(+) patients in the IgM(+) and IgG(+) group converted to IgM(-), and the percentages of NK cells and B lymphocytes in these patients were significantly increased at week 4. CONCLUSIONS: The changes of serum IgM and IgG are closely related to immunity in patients in the recovery stage. However, immunity does not recover when the patients test negative for these antibodies.