Treatment Of Autoimmune Diseases Research Articles

MICROBIOTA TRANSPLANTATION AND ITS ROLE IN AUTOIMUNNE DISEASES: LITERATURE REVIEW

Introduction: Autoimmune diseases affect around 10% of the world population. Most of these are complex diseases caused by the interaction between genetic, epigenetic and environmental factors. Furthermore, autoimmune diseases have become the third largest chronic disease, after cardiovascular diseases and cancer. The human microbiome may play an important role in autoimmunity, as loss of immunological tolerance may be caused by changes in microbial composition. Microorganisms can provoke an immune response against the host if tolerance mechanisms fail for several reasons. Objective: To carry out a literature review evaluating the role of microbiota transplantation in patients with autoimmune diseases. Method: This is a bibliographic review, with a search for articles carried out through the Virtual Health Library (VHL), LILACS, PubMed and Scopus for all relevant articles that included in their theme the involvement of microbiota transplantation and its role in autoimmune diseases. Final considerations: Fecal microbiota transplantation (FMT) has a very important role for patients with autoimmune diseases (AD), especially individuals with type 1 diabetes mellitus, systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis, in which FMT has demonstrated promising results. for the treatment of these individuals. However, as the literature is still quite limited in relation to the type of donor and ideal dosage, in addition to the route of administration and treatment interval for each type of autoimmune disease, it is important to carry out targeted studies with the aim of evaluating the effects. benefits of FMT targeted to each AD, in addition to the possible adverse events and the particular characteristics of this procedure in the treatment of ADs associated with changes in intestinal flora.

Development of Potent MALT1 Inhibitors Featuring a Novel "2-Thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one" Scaffold for the Treatment of B Cell Lymphoma.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has emerged as a novel and promising therapeutic target for the treatment of lymphomas and autoimmune diseases. Herein, we reported a new class of MALT1 inhibitors featuring a novel "2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one" scaffold developed by structure-based drug design. Structure-activity relationship studies finally led to the discovery of MALT1 inhibitor 10m, which covalently and potently inhibited MALT1 protease with the IC50 value of 1.7 μM. 10m demonstrated potent and selective antiproliferative activity against ABC-DLBCL and powerful ability to induce HBL1 apoptosis. 10m also effectively downregulated the activities of MALT1 and its downstream signal pathways. Furthermore, 10m induced upregulation of mTOR and PI3K-Akt signals and exhibited a synergistic antitumor effect with Rapamycin in HBL1 cells. More importantly, 10m remarkably suppressed the tumor growth both in the implanted HBL1 and TMD8 xenograft models. Collectively, this work provides valuable MALT1 inhibitors with a distinct core structure.

Nutritional interventions as modulators of the disease activity for idiopathic inflammatory myopathies: a scoping review.

Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.

Rituximab in the Management of Autoimmune Bullous Diseases: A Treatment-Resistant Case Series from a Single Central European Referral Center.

Background and Objectives: Rituximab (RTX) has been the predominant treatment for autoimmune bullous diseases (AIBDs). The objective of this research was to assess the advantages and safety characteristics of RTX treatment in individuals with AIBD. This assessment focused on clinical remission and a reduction in glucocorticosteroid usage, its effect on the titers of autoantibodies targeting desmoglein-1 (DSG-1) and desmoglein-3 (DSG-3), and adverse occurrences during a 12-month follow-up period in a dermatology department within a Central European university context. Materials and Methods: Our case series involved eleven patients, including eight patients with pemphigus vulgaris, two with pemphigus foliaceus, and one with epidermolysis bullosa acquisita. They received a 1 g dose of rituximab, repeated over a two-week interval. Results: The reduction in a prednisone-equivalent dosage after 2, 6, and 12 months following the second RTX infusion was 65.05%, 73.99%, and 76.93%, in that order. The titers of antibodies against DSG-1 exhibited reductions of 43.29%, 75.86%, and 54.02% at 2, 6, and 12 months, respectively. By contrast, the antibody concentrations targeting DSG-3 displayed a decrease of 27.88%, 14.48%, and 5.09% at the corresponding time points. Over the course of the 12-month monitoring period, 18.18% of patients experienced disease relapse, while the remaining individuals achieved either complete or partial remission with minimal or no therapy. Adverse effects were noted in 36.36% of the patient population; they were mild, and no serious adverse effects were reported. Conclusions: RTX represents an efficacious and well-tolerated therapeutic option for the management of AIBD and merits consideration in cases of refractory AIBD. However, further research is imperative to delineate the most optimal dosage, dosing frequency, and total quantity of maintenance infusions required. Additionally, there is a compelling need for studies that explore the impact of RTX on individuals with AIBD who do not exhibit a significant reduction in anti-desmoglein autoantibody levels.

Clinical and experimental treatment of primary humoral immunodeficiencies.

Selective IgA deficiency (sIgAD), common variable immunodeficiency (CVID), and transient hypogammaglobulinemia of infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular patomechanism and a similar genetic background. In this review, we discuss both similarities and differences of these three humoral immunodeficiencies, focusing on current and novel therapeutic approaches. We summarize immunoglobulin substitution, antibiotic prophylaxis, treatment of autoimmune diseases, and other common complications, i.e. cytopenias, gastrointestinal complications, and granulomatous disease. We discuss novel therapeutic approaches such as allogenic stem cell transplantation and therapies targeting-specific proteins, dependent on the patient's genetic defect. The diversity of possible therapeutics models results from a great heterogeneity of the disease variants, implying the need of personalized medicine approach as a future of primary humoral immunodeficiencies treatment.

Comprehensive Exploration of Antinuclear Antibodies (ANAs): Unveiling Clinical Significance, Associations with Cancer, and the Nuances of Differential Diagnosis in Positive ANA Patients

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs’ diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Trends in the synthetic polymer delivery of RNA.

Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID-19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non-vaccine-related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.

Therapeutic Administration of Trichuris Suis Ova as Alternative Treatment of Multiple Sclerosis: A Mini-Review

Autoimmune disorders like Multiple Sclerosis (MS), rheumatoid arthritis, and inflammatory bowel disease occur when your body’s mounts a response to itself. Genetic predisposition is responsible for some of the response, while environmental factors contribute as well. Multiple sclerosis is a debilitating disease that impacts the brain, spinal cord, and optic nerves. There is an inverse correlation of exposure to helminths with prevalence of MS in helminth-endemic countries. This may be due to the alteration with the immunological response to antigens that accompanies the exposure to helminths. With the different molecules secreted by helminths that enhance tolerance in the human immune system to survive, interest in these secretory molecules for developing novel treatments against autoimmune diseases grew. There has been focus on Trichuris Suis Ova (TSO), eggs of a porcine helminth, as biologic for the treatment of autoimmune diseases. The results for TSO-based therapies as treatment for MS have been promising, in addition to these therapies being safe and well tolerated. However, there have been some contrasting reports with clinical outcomes. Therapeutic administration of T. suis ova or other products of this helminth as alternative treatment of multiple sclerosis should be further studied and thus provide enhancements in these immunotherapies.

Hydroxytyrosol Alleviates Methotrexate-Induced Pulmonary Fibrosis in Rats: Involvement of TGF-β1, Tissue Factor, and VEGF.

Methotrexate (MTX) is an indispensable drug used for the treatment of many autoimmune and cancerous diseases. However, its clinical use is associated with serious side effects, such as lung fibrosis. The main objective of this study is to test the hypothesis that hydroxytyrosol (HT) can mitigate MTX-induced lung fibrosis in rats while synergizing MTX anticancer effects. Pulmonary fibrosis was induced in the rats using MTX (14 mg/kg/week, per os (p.o.)). The rats were treated with or without HT (10, 20, and 40 mg/kg/d p.o.) or dexamethasone (DEX; 0.5 mg/kg/d, intraperitoneally (i.p.)) for two weeks concomitantly with MTX. Transforming growth factor beta 1 (TGF-β1), interleukin-4 (IL-4), thromboxane A2 (TXA2), vascular endothelial growth factor (VEGF), 8-hydroxy-2-deoxy-guanosine (8-OHdG), tissue factor (TF) and fibrin were assessed using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and RT-PCR. Pulmonary fibrosis was manifested by an excessive extracellular matrix (ECM) deposition and a marked increase in TGF-β1 and IL-4 in lung tissues. Furthermore, cotreatment with HT or dexamethasone (DEX) significantly attenuated MTX-induced ECM deposition, TGF-β1, and IL-4 expression. Similarly, HT or DEX notably reduced hydroxyproline contents, TXA2, fibrin, and TF expression in lung tissues. Moreover, using HT or DEX downregulated the gene expression of TF. A significant decrease in lung contents of VEGF, IL-8, and 8-OHdG was also observed in HT + MTX- or DEX + MTX -treated animals in a dose-dependent manner. Collectively, the results of our study suggest that HT might represent a potential protective agent against MTX-induced pulmonary fibrosis.

P166 Optimizing PD-1 agonist signaling with membrane proximal binding of rosnilimab, a clinical stage PD-1 agonist IgG1 antibody

Abstract Background Checkpoint agonism represents a promising class of therapies for the treatment of autoimmune and inflammatory diseases, including ulcerative colitis (UC), where unmet needs persist despite available therapies. Binding to membrane proximal regions of checkpoint receptors, together with Fc interactions with receptors on opposing cells, can contribute to tight immune synapse formation between the immune cell and antigen presenting cell. This has been proposed to improve potency of agonistic signaling by excluding phosphatases such as CD45 from the immune synapse and promoting receptor clustering. Optimization of these characteristics results in improved agonism and depletion, with the potential for restoration of immune balance and broader clinical outcomes. Rosnilimab was engineered to leverage these important characteristics. It is a PD-1 agonist IgG1 antibody designed to optimize inhibitory signaling through the PD-1 receptor and to deplete PD-1high pathogenic T cells. Rosnilimab is in Phase 2 clinical development for UC and rheumatoid arthritis. Methods Mutations to surface exposed regions of the PD-1 extracellular domain were made and surface plasmon resonance was used to infer the epitopes of PD-1 agonist molecules from resulting changes to binding. Membrane proximal and distal binding antibodies were studied in in vitro functional assays to assess T cell proliferation and antibody-dependent cellular toxicity. Results Epitopes of agonistic antibodies were mapped to locations on the PD-1 receptor. The membrane proximal binding epitope of rosnilimab was confirmed and binding epitopes for other reference antibodies (ref) were identified. Rosnilimab and a membrane distally binding antibody (ref 1) were selected for comparison in functional assays. Rosnilimab demonstrated greater reduction of T cell proliferation and depletion of PD-1+ T cells compared to ref 1, consistent with the hypothesis that membrane proximal binding improves agonistic activity and target cell depletion. Conclusion By targeting and leveraging inhibitory immune regulatory mechanisms to modulate the pathogenic T cells driving disease, there is an opportunity to dampen the inflammatory cycle and restore immune balance via agonism. Rosnilimab binds to a membrane proximal region of the PD-1 receptor, resulting in potent reduction of T cell proliferation and depletion of PD-1high T cells. These mechanistic data, translational in vivo and in vitro data, robust Phase 1 healthy volunteer data, and unmet needs in UC provide rationale for an ongoing global Phase 2 study of rosnilimab in UC (NCT06127043).

Restoring immune tolerance in pemphigus vulgaris

Intravenous immunoglobulin (IVIg), a preparation of polyclonal serum IgG pooled from numerous blood donors, has been used for nearly three decades and is proving to be an efficient treatment for many autoimmune blistering diseases, including pemphigus vulgaris (PV). Despite its widespread use and therapeutic success, its mechanisms of action are not completely understood. Some of its anti-inflammatory and immunomodulatory actions have been studied. In this study, the authors present a twenty-year follow-up of 21 patients with clinical and immunopathological confirmed PV, treated with IVIg as monotherapy, according to an established published protocol. IVIg therapy produced long-term sustained, clinical, serological, and immunopathological remission. For 20 y, these patients received no drugs and experienced no disease. This observation suggests that there was the establishment of immune balance or restoration of immune regulation in these PV patients. Twelve (57%) patients experienced no relapse during follow-up. Six (29%) patients experienced a relapse due to acute stress or post-coronavirus infection and/or vaccination. Reinstitution of IVIg resulted in prompt sustained recovery. Three (14.2%) patients, in clinical and serological remission, died due to unrelated causes. No severe adverse effects from IVIg were documented in all 21 patients. The simultaneous or sequential anti-inflammatory and immunomodulatory effects of IVIg may have influenced the long-term clinical remission observed. This study provides a human prototype to examine the pathophysiology of autoimmunity and a model to study immune regulation and mechanisms that can facilitate restoring immune tolerance.

Hydroxychloroquine-Induced Hypoglycemia in a Patient Without Diabetes.

Hydroxychloroquine is a disease-modifying antirheumatic drug commonly used in the treatment of autoimmune diseases. Although rare, hydroxychloroquine is associated with hypoglycemia in patients with or without diabetes due to its ability to alter insulin metabolism. There have been several cases described in the literature, but none of which, to our knowledge, detail follow-up and time to resolution of hypoglycemia. We describe a 55-year-old female who presents for episodes of hypoglycemia. She reported hypoglycemic symptoms and fasting blood glucoses in the 60-70s mg/dL regularly. Based on the Naranjo adverse drug reaction probability scale, hydroxychloroquine was the probable etiology of her hypoglycemic episodes due to the improvement at her 3-month follow up appointment after discontinuing the drug. Providers should be mindful of the hypoglycemia risk when using hydroxychloroquine and be aware that the effects may take an extended amount of time to resolve given the drug's long half-life.

Transdermally delivered tolerogenic nanoparticles induced effective immune tolerance for asthma treatment

Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.

Transcriptional Coactivator BOB1 (OBF1, OCA-B) Modulates the Specificity of DNA Recognition by the POU-Domain Factors OCT1 and OCT2 in a Monomeric Configuration.

BOB1, a mammalian lymphocyte-specific transcriptional coactivator of the transcription factors OCT1 and OCT2 (OCT1/2), plays important roles in normal immune responses, autoimmunity, and hematologic malignancies. The issue of a DNA sequence preference change imposed by BOB1 was raised more than two decades ago but remains unresolved. In this paper, using the EMSA-SELEX-Seq approach, we have reassessed the intrinsic ability of BOB1 to modulate the specificity of DNA recognition by OCT1 and OCT2. Our results have reaffirmed previous conclusions regarding BOB1 selectivity towards the dimer configuration of OCT1/2. However, they suggest that the monomeric configuration of these factors, assembled on the classical octamer ATGCAAAT and related motifs, are the primary targets of BOB1. Our data further specify the DNA sequence preference imposed by BOB1 and predict the probability of ternary complex formation. These results provide an additional insight into the action of BOB1-an essential immune regulator and a promising molecular target for the treatment of autoimmune diseases and hematologic malignancies.

Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method

BackgroundDaratumumab is a monoclonal antibody that targets CD38, a transmembrane protein expressed on many cells including RBCs and to a greater extent on myeloma cells. It has been used for treatment of multiple myeloma and autoimmune diseases. Transfusion management of patients on such therapy can be challenging as these drugs cross-react with RBC surface antigens and cause panreactivity. Material and methodsA retrospective study of the 68 patients treated with anti-CD38 from 2018–2023 was carried out. Data regarding transfusion history and antibody screens were analyzed. Depending whether they had immunohematological work-up before or during the treatment- DAT, antibody screen (CAT and tube), RBC pheno/genotyping and serologic cross-matches (CAT and tube) were performed for each patient. All cases with positive CAT IAT were retested in LISS-tube and cross-matches were performed with phenotypically matched units in LISS-tube. ResultsAntibody screen has shown panagglutination with all panel cells with low and variable agglutination intensity (weak to 2 +). Panagglutination remained positive for 1 − 6 months after drug cessation. Positive DAT was seen in 60,6% patients, while autocontrol was negative. Ficin treated panel-cells eliminated nonspecific reactivity. LISS-tube antibody screen and cross-matches were negative for all patients, apart from 3 patients who had preexisting antibodies. No new antibodies were detected during the course of the study. ConclusionAmong study group there were no newly identified alloantibodies, meaning that the policy of transfusing them with matched RBCs and performing IAT/cross-matches in tube is a safe and effective policy according to the findings of this study.

Effect of treatment with original or biosimilar adalimumab on SARS-CoV2 vaccination antibody titers

The technological process of production of biosimilars determines the degree of biosimilarity to the original biological drug. In particular, the focus is on the similarity of immunogenic responses. The primary endpoint of our retrospective study was to find the differences in SARS-CoV-2 antibody amount between patients treated with original adalimumab and biosimilar adalimumab MSB11022 (Idacio) and the differences in the SARS-CoV-2 antibody amount between patients treated with and without biological treatment. We collected the gender, autoimmune disease type, age, and treatment data of the patients in the outpatient clinic MEDICAL PLUS, s.r.o., Uherske Hradiste. These patients suffer from autoimmune rheumatic diseases. All patients received the mRNA vaccine (Pfizer/BioNTech – BNT162b2), with a 21-day (interquartile range, 21–24) gap between the two vaccinations. Patients receiving adalimumab were able to develop cellular immune responses after the second vaccination dose, as well as the individuals without adalimumab. In the period of 6–23 weeks after the second vaccination dose (D63 – D182), the SARS-CoV-2 antibody levels did not change significantly in the patients receiving the original adalimumab, while in the patients receiving biosimilar adalimumab a significant decrease was revealed. A statistically significant difference in the SARS-CoV-2 antibody amount between the patients without biological treatment (median: 504.3 U/mL) and with biological treatment (Original and Biosimilar – median: 47.2 and 28.2 U/mL, respectively) was confirmed on day 182. According to our observation, the effect of the treatment type on the increase/decrease of antibodies over time is dominant, while the impact of other variables (gender, methotrexate treatment, autoimmune disease type, and age) was confirmed as insignificant or minor.

Mechanisms of Stem Cells and Their Secreted Exosomes in the Treatment of Autoimmune Diseases.

Stem cells play a therapeutic role in many diseases by virtue of their strong self-renewal and differentiation abilities, especially in the treatment of autoimmune diseases. At present, the mechanism of the stem cell treatment of autoimmune diseases mainly relies on their immune regulation ability, regulating the number and function of auxiliary cells, anti-inflammatory factors and proinflammatory factors in patients to reduce inflammation. On the other hand, the stem cell- derived secretory body has weak immunogenicity and low molecular weight, can target the site of injury, and can extend the length of its active time in the patient after combining it with the composite material. Therefore, the role of secretory bodies in the stem cell treatment of autoimmune diseases is increasingly important.

Slightly photo-crosslinked chitosan/silk fibroin hydrogel adhesives with hemostasis and anti-inflammation for pro-healing cyclophosphamide-induced hemorrhagic cystitis

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity.

Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We identified that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only an enrichment of effector-like Tregs, but also activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.