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1.
Carbohydr Polym ; 339: 122214, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823900

The polysaccharide, RGP2, was isolated from Russula griseocarnosa and its immunostimulatory effects were confirmed in cyclophosphamide (CTX)-induced immunosuppressed mice. Following purification via chromatography, structural analysis revealed that RGP2 had a molecular weight of 11.82 kDa and consisted of glucose (Glc), galactose (Gal), mannose, glucuronic acid and glucosamine. Bond structure analysis and nuclear magnetic resonance characterization confirmed that the main chain of RGP2 was formed by →6)-ß-D-Glcp-(1→, →3)-ß-D-Glcp-(1→ and →6)-α-D-Galp-(1→, which was substituted at O-3 of →6)-ß-D-Glcp-(1→ by ß-D-Glcp-(1→. RGP2 was found to ameliorate pathological damage in the spleen and enhance immune cell activity in immunosuppressed mice. Based on combined multiomics analysis, RGP2 altered the abundance of immune-related microbiota (such as Lactobacillus, Faecalibacterium, and Bacteroides) in the gut and metabolites (uridine, leucine, and tryptophan) in the serum. Compared with immunosuppressed mice, RGP2 also restored the function of antigen-presenting cells, promoted the polarization of macrophages into the M1 phenotype, positively affected the differentiation of helper T cells, and inhibited regulatory T cell differentiation through the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, ultimately exerting an immune boosting function. Overall, our findings highlight therapeutic strategies to alleviate CTX-induced immunosuppression in a clinical setting.


Basidiomycota , Cell Differentiation , Glucans , Animals , Mice , Basidiomycota/chemistry , Glucans/chemistry , Glucans/pharmacology , Glucans/isolation & purification , Cell Differentiation/drug effects , T-Lymphocytes/drug effects , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Male , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Cyclophosphamide/pharmacology , Mice, Inbred BALB C , Gastrointestinal Microbiome/drug effects
2.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200251, 2024 Jul.
Article En | MEDLINE | ID: mdl-38838284

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear. METHODS: By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors. RESULTS: Patients with MS showed a reduced frequency of CD4+ T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs. DISCUSSION: Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.


Multiple Sclerosis, Relapsing-Remitting , Natalizumab , T-Lymphocytes, Regulatory , Humans , T-Lymphocytes, Regulatory/immunology , Adult , Female , Male , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/pharmacology , Middle Aged , Thymus Gland/immunology , Immunologic Factors/pharmacology , Young Adult
3.
Support Care Cancer ; 32(7): 407, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833106

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.


Lenalidomide , Medication Adherence , Multiple Myeloma , Social Class , Thalidomide , Humans , Multiple Myeloma/drug therapy , Male , Retrospective Studies , Medication Adherence/statistics & numerical data , Female , Middle Aged , Aged , Thalidomide/therapeutic use , Thalidomide/analogs & derivatives , Thalidomide/administration & dosage , Lenalidomide/administration & dosage , Lenalidomide/therapeutic use , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/administration & dosage , Immunomodulating Agents/pharmacology , Texas , Aged, 80 and over , Adult
4.
PLoS One ; 19(5): e0302913, 2024.
Article En | MEDLINE | ID: mdl-38728358

In the fight against antimicrobial resistance, host defense peptides (HDPs) are increasingly referred to as promising molecules for the design of new antimicrobial agents. In terms of their future clinical use, particularly small, synthetic HDPs offer several advantages, based on which their application as feed additives has aroused great interest in the poultry sector. However, given their complex mechanism of action and the limited data about the cellular effects in production animals, their investigation is of great importance in these species. The present study aimed to examine the immunomodulatory activity of the synthetic HDP Pap12-6 (PAP) solely and in inflammatory environments evoked by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (Poly I:C), in a primary chicken hepatocyte-non-parenchymal cell co-culture. Based on the investigation of the extracellular lactate dehydrogenase (LDH) activity, PAP seemed to exert no cytotoxicity on hepatic cells, suggesting its safe application. Moreover, PAP was able to influence the immune response, reflected by the decreased production of interleukin (IL)-6, IL-8, and "regulated on activation, normal T cell expressed and secreted"(RANTES), as well as the reduced IL-6/IL-10 ratio in Poly I:C-induced inflammation. PAP also diminished the levels of extracellular H2O2 and nuclear factor erythroid 2-related factor 2 (Nrf2) when applied together with Poly I:C and in both inflammatory conditions, respectively. Consequently, PAP appeared to display potent immunomodulatory activity, preferring to act towards the cellular anti-inflammatory and antioxidant processes. These findings confirm that PAP might be a promising alternative for designing novel antimicrobial immunomodulatory agents for chickens, thereby contributing to the reduction of the use of conventional antibiotics.


Chickens , Hepatocytes , Lipopolysaccharides , Poly I-C , Animals , Hepatocytes/drug effects , Hepatocytes/immunology , Hepatocytes/metabolism , Poly I-C/pharmacology , Lipopolysaccharides/pharmacology , Immunologic Factors/pharmacology , Teichoic Acids/pharmacology , Cells, Cultured , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Coculture Techniques , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Cytokines/metabolism , Antimicrobial Cationic Peptides/pharmacology
5.
Medicine (Baltimore) ; 103(19): e38103, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728448

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by reduced activity of the von Willebrand factor-cleaving protease (ADAMTS13), which can be life-threatening. The patient reported in this case study also had concurrent Sjögren syndrome and renal impairment, presenting multiple symptoms and posing a great challenge in treatment. PATIENT CONCERNS: A 25-year-old woman in the postpartum period visited the hospital due to indifference in consciousness for more than 1 day following cesarean section 8 days prior. DIAGNOSIS: Notable decreases were observed in platelets, hemoglobin, creatinine, and ADAMTS13 levels. After a consultative examination by an ophthalmologist, she was diagnosed with retinal hemorrhage in the right eye and dry eye syndrome in both eyes. INTERVENTIONS: Having been diagnosed with TTP with Sjögren syndrome and renal impairment, she received repeated treatments with plasmapheresis combined with rituximab. OUTCOMES: Following treatment and during the follow-up period, the patient's platelet counts and bleeding symptoms significantly improved. LESSONS: TTP has a high mortality rate, and when combined with Sjögren syndrome and renal impairment, it poses an even greater challenge in treatment. However, after administering standard plasmapheresis combined with rituximab treatment, the treatment outcome is favorable.


Plasmapheresis , Purpura, Thrombotic Thrombocytopenic , Rituximab , Sjogren's Syndrome , Humans , Female , Sjogren's Syndrome/complications , Sjogren's Syndrome/therapy , Plasmapheresis/methods , Adult , Purpura, Thrombotic Thrombocytopenic/therapy , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/drug therapy , Rituximab/therapeutic use , Rituximab/administration & dosage , Combined Modality Therapy , Renal Insufficiency/therapy , Renal Insufficiency/etiology , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage
6.
Pediatr Rheumatol Online J ; 22(1): 50, 2024 May 01.
Article En | MEDLINE | ID: mdl-38693550

BACKGROUND: This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. METHODS: We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. RESULTS: The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. CONCLUSION: Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.


Drug Resistance , Echocardiography , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Male , Female , Cross-Sectional Studies , Echocardiography/methods , Child, Preschool , Infant , Child , Uveitis/etiology , Uveitis/epidemiology , Conjunctivitis/etiology , Conjunctivitis/epidemiology , Incidence , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Blood Sedimentation , Leukocyte Count , Immunologic Factors/therapeutic use , Platelet Count
7.
Molecules ; 29(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38731567

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.


Macrophages , Phagocytosis , Polygonatum , Polysaccharides , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Polygonatum/chemistry , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Animals , Phagocytosis/drug effects , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , RAW 264.7 Cells , Cytokines/metabolism , Cell Proliferation/drug effects , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/isolation & purification , Molecular Weight
8.
Bull Exp Biol Med ; 176(5): 585-590, 2024 Mar.
Article En | MEDLINE | ID: mdl-38724813

Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.


Antipsychotic Agents , Chlorpromazine , Diazepam , Leukocyte Elastase , Humans , Leukocyte Elastase/metabolism , Chlorpromazine/pharmacology , Diazepam/pharmacology , Antipsychotic Agents/pharmacology , Diclofenac/pharmacology , Nootropic Agents/pharmacology , Tranquilizing Agents/pharmacology , Immunologic Factors/pharmacology , Vinca Alkaloids
9.
Adv Appl Microbiol ; 127: 45-142, 2024.
Article En | MEDLINE | ID: mdl-38763529

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.


Fungal Polysaccharides , Fungal Polysaccharides/chemistry , Humans , Animals , Agaricales/chemistry , Agaricales/metabolism , Antioxidants/chemistry , Antioxidants/pharmacology , Immunologic Factors/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology
10.
Skin Therapy Lett ; 29(3): 1-4, 2024 May.
Article En | MEDLINE | ID: mdl-38781951

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.


Immunoglobulins, Intravenous , Skin Diseases , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Skin Diseases/drug therapy , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage
12.
Int J Mol Sci ; 25(10)2024 May 14.
Article En | MEDLINE | ID: mdl-38791372

Mulberry is a rapidly growing plant that thrives in diverse climatic, topographical, and soil types, spanning temperature and temperate countries. Mulberry plants are valued as functional foods for their abundant chemical composition, serving as a significant reservoir of bioactive compounds like proteins, polysaccharides, phenolics, and flavonoids. Moreover, these compounds displayed potent antioxidant activity by scavenging free radicals, inhibiting reactive oxygen species generation, and restoring elevated nitric oxide production induced by LPS stimulation through the downregulation of inducible NO synthase expression. Active components like oxyresveratrol found in Morus demonstrated anti-inflammatory effects by inhibiting leukocyte migration through the MEK/ERK signaling pathway. Gallic and chlorogenic acids in mulberry leaves (ML) powder-modulated TNF, IL-6, and IRS1 proteins, improving various inflammatory conditions by immune system modulation. As we delve deeper into understanding its anti-inflammatory potential and how it works therapeutically, it is crucial to refine the extraction process to enhance the effectiveness of its bioactive elements. Recent advancements in extraction techniques, such as solid-liquid extraction, pressurized liquid extraction, superficial fluid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction, are being explored. Among the extraction methods tested, including Soxhlet extraction, maceration, and ultrasound-assisted extraction (UAE), UAE demonstrated superior efficiency in extracting bioactive compounds from mulberry leaves. Overall, this comprehensive review sheds light on the potential of mulberry as a natural immunomodulatory agent and provides insights into its mechanisms of action for future research and therapeutic applications.


Morus , Plant Extracts , Morus/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Humans , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Plant Leaves/chemistry
13.
Int J Mol Sci ; 25(10)2024 May 14.
Article En | MEDLINE | ID: mdl-38791391

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.


Antibodies, Monoclonal, Humanized , Humans , Female , Male , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Middle Aged , Retrospective Studies , B-Lymphocytes/immunology , B-Lymphocytes/drug effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Treatment Outcome , COVID-19/immunology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/immunology , SARS-CoV-2/immunology , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use
14.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200254, 2024 Jul.
Article En | MEDLINE | ID: mdl-38728609

OBJECTIVES: We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding. METHODS: This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist. RESULTS: A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation. DISCUSSION: This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions. CLASSIFICATION OF EVIDENCE: This provides Class IV evidence. It is a single observational study without controls.


Autoantibodies , CTLA-4 Antigen , Encephalitis , Haploinsufficiency , Hashimoto Disease , Receptors, AMPA , Humans , Male , Child , Encephalitis/diagnosis , Encephalitis/drug therapy , Encephalitis/immunology , Hashimoto Disease/diagnosis , Hashimoto Disease/drug therapy , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Receptors, AMPA/immunology , Rituximab/administration & dosage , Rituximab/therapeutic use , Immunologic Factors
15.
J Med Case Rep ; 18(1): 245, 2024 May 13.
Article En | MEDLINE | ID: mdl-38736000

BACKGROUND: Natalizumab is a monoclonal antibody used to treat patients with relapsing-remitting multiple sclerosis. Anemia is a recognized side effect, but it is usually mild and of a short duration when natalizumab is stopped. Here, we describe a case of a young woman with severe and especially long lasting anemia associated with treatment with natalizumab, persisting up to a year after treatment was stopped. CASE PRESENTATION: A 24 year-old Caucasian woman with relapsing-remitting multiple sclerosis developed severe transfusion dependent anemia after 27 infusions with natalizumab, which was her first and only treatment for her multiple sclerosis. Extensive hematologic diagnostics did not reveal any malignant cause or any other plausible non-malignant cause for her anemia. The bone marrow was found to be hypercellular, with a maturation arrest of the erythropoiesis and with grade 1-2 fibrosis. No specific treatment for the anemia was given. The hemoglobin level showed signs of spontaneous increase after nearly one year after natalizumab was discontinued. CONCLUSION: Severe anemia can be caused by treatment with natalizumab. This case adds information to the few other similar reported cases, demonstrating the potential duration of the anemia, as well as detailed description of hematologic findings. The mechanism is most likely due to inhibition of α4 subunit of the α4ß1-integrin, which is present on both lymphocytes and erythroid precursor cells.


Anemia , Multiple Sclerosis, Relapsing-Remitting , Natalizumab , Humans , Natalizumab/adverse effects , Natalizumab/therapeutic use , Female , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Anemia/chemically induced , Young Adult , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use
16.
PLoS One ; 19(5): e0304713, 2024.
Article En | MEDLINE | ID: mdl-38820477

Argentatins are secondary metabolites synthesized by guayule (Parthenium argentatum A. Gray) with numerous potential medical applications. In addition to inhibiting insect growth, they are endowed with several pharmacological properties including antimicrobial and antitumorigenic activity. However, their potential as immunomodulators remains unexplored. The aim of the present study was to investigate whether argentatins can modulate the function of the immune system. Human mesenchymal stem cells were treated with argentatins and the production of several anti- and proinflammatory cytokines was evaluated. The effect of argentatins on the polarization of CD4+ T-lymphocytes and macrophages was also assessed. Results demonstrated that argentatins can modulate the production of proinflammatory cytokines and the polarization of cellular phenotypes, including Th2 lymphocytes and M1 macrophages. These findings suggest that argentatins are promising therapeutic agents in autoimmune or allergic diseases, and open new perspectives for the investigation of argentatins in immune response and in the development of more targeted and effective immunomodulatory therapies.


Cytokines , Humans , Cytokines/metabolism , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Immunologic Factors/pharmacology , Immunomodulating Agents/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/drug effects
17.
Mult Scler ; 30(7): 857-867, 2024 Jun.
Article En | MEDLINE | ID: mdl-38767224

BACKGROUND: Ocrelizumab (OCR) is an anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting and primary-progressive multiple sclerosis (MS). We aimed to evaluate the effectiveness of an individualized OCR extended interval dosing (EID), after switching from standard interval dosing (SID). METHODS: This was a retrospective, observational, single-centre study including MS patients regularly followed at the Neurocenter of Southern Switzerland. After a cumulative OCR dose ⩾1200 mg, stable patients were switched to EID (OCR infusions following CD19+ 27+ memory B cell repopulation). RESULTS: A total of 128 patients were included in the study, and 113 (88.3%) were switched to EID with a median interval of 9.9 (8.8-11.8) months between infusions. No clinical relapses occurred; 2 (1.8%) patients experienced disability worsening. Three (2.7%) and 2 (1.8%) patients experienced new T2 brain and spinal lesions, respectively. There was a mild decrease in IgG and IgM concentrations during both SID and EID OCR regimens (ß = -0.23, p = 0.001 and ß = -0.07, p < 0.001, respectively). CONCLUSION: Switch to personalized dosing of OCR based on CD19+ 27+ memory B cell repopulation led to a great extension of the interval between infusions, with maintained clinical and radiological efficacy. Given the potential advantages in terms of safety and health costs, EID OCR regimens should be further investigated.


Antibodies, Monoclonal, Humanized , Memory B Cells , Humans , Female , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/pharmacology , Male , Adult , Retrospective Studies , Middle Aged , Memory B Cells/immunology , Immunologic Factors/administration & dosage , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/immunology , Treatment Outcome , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology
18.
Molecules ; 29(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38792148

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITYTM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R2, 0.9971-0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.


Astragalus propinquus , Drugs, Chinese Herbal , Monosaccharides , Polysaccharides , Chromatography, High Pressure Liquid/methods , Monosaccharides/analysis , Polysaccharides/chemistry , Polysaccharides/analysis , Astragalus propinquus/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Mice , Animals , RAW 264.7 Cells , Astragalus Plant/chemistry , Immunologic Factors/analysis , Immunologic Factors/chemistry
19.
J Clin Neurosci ; 125: 76-82, 2024 Jul.
Article En | MEDLINE | ID: mdl-38759351

BACKGROUND: Intravenous immunoglobulin (IVIg) and plasmapheresis (PLEX) are recommended in moderate to severe Guillain-Barré Syndrome (GBS), but there is paucity of studies evaluating its effect on nerve conduction studies (NCS). We report the effect of IVIg and PLEX on the NCS parameters and clinical outcomes compared to natural course (NC) of GBS patients. METHOD: Moderate to severe GBS patients were included based on clinical, cerebrospinal fluid, and NCS finding. Six motor and sensory nerves were evaluated at admission, one month and 3 months, and NCS subtyping was done. Axonal and demyelination burden in motor nerves and early reversible conduction block (ERCB) were noted. Patients receiving IVIg, PLEX or on NC were noted. Outcome was defined at 3 months into complete, partial and poor using a 0-6 GBS Disability Scale (GBSDS). RESULT: Seventy-two patients were included, whose median age was 36 years and 22(30.6 %) were females. 44 patients received IVIg, 9 PLEX and 19 were in NC, and they had comparable peak disability. AIDP was the dominant subtype at admission (58.3 %), which remained so at 3 months (50 %). The shift of subtypes was the highest from the equivocal group followed by AMAN and the least from AIDP. IVIg and PLEX group had more reduction in axonal burden and had ERCB compared to NC. 33(44 %) patients had complete recovery, and 40(55.5 %) patients had concordance in clinical and neurophysiological outcome. CONCLUSION: Transition of GBS subtype may occur at follow-up from all the subtypes, the highest from the equivocal and the lowest from the AIDP group. IVIg/PLEX treatment may help in reducing conduction block and axonal burden.


Guillain-Barre Syndrome , Immunoglobulins, Intravenous , Neural Conduction , Plasmapheresis , Humans , Guillain-Barre Syndrome/therapy , Guillain-Barre Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Female , Male , Adult , Plasmapheresis/methods , Neural Conduction/physiology , Neural Conduction/drug effects , Middle Aged , Young Adult , Treatment Outcome , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage , Adolescent
20.
Int J Biol Macromol ; 270(Pt 2): 132497, 2024 Jun.
Article En | MEDLINE | ID: mdl-38763236

To alleviate the adverse effects of chemotherapy and bolster immune function, a novel polysaccharide derived from Sargassum fusiforme named as SFP-αII. The structural composition of SFP-αII predominantly consisted of guluronic and mannuronic acids in a molar ratio of 33.8:66.2, with an average molecular weight of 16.5 kDa. Its structure was primarily characterized by →4)-α-GulA-(1 â†’ and →4)-ß-ManA-(1 â†’ linkages confirmed by FT-IR, methylation, and NMR analyses. The absence of a triple-helix structure was in SFP-αII was confirmed using circular dichroism and Congo red dye assays. The dimensions varied with lengths ranging from 20 nm up to 3 µm revealed by atomic force microscopy (AFM). SFP-αII has been found to enhance immunomodulatory activity in cyclophosphamide (CTX)-induced immunosuppressed mice. This was evidenced by improvements in immune organ indices, cytokine levels, and the release of nitric oxide (NO). Specifically, SFP-αII mitigated immunosuppression by upregulating the secretion of IL-1ß (167.3 %) and TNF-α (227.1 %) at a dose of 400 mg/kg, compared with the CTX group in macrophages. Ultimately, SFP-αII may serve as a mechanism for immune enhancement through modulation of TLR4-mediated NF-κB and MAPK signaling pathways. This integration of traditional Chinese and Western medicine, leveraging SFP-αII as a potential functional food could be pivotal in alleviating immunosuppressive side effects in CTX treatment.


Polysaccharides , Sargassum , Sargassum/chemistry , Animals , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Cytokines/metabolism , RAW 264.7 Cells , Cyclophosphamide/pharmacology , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Male , NF-kappa B/metabolism , Nitric Oxide/metabolism , Molecular Weight , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Edible Seaweeds
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