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1.
Zinc and vitamin C intake increases spike and neutralising antibody production following SARS-CoV-2 infection.
Quek, AML, Ooi, DSQ, Teng, O, Chan, CY, Ng, GJL, Ng, MY, Yee, S, Cheong, EW, Weng, R, Cook, AR, et al
Clinical and translational medicine. 2022;(2):e731
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Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.
Loke, P, Orsini, F, Lozinsky, AC, Gold, M, O'Sullivan, MD, Quinn, P, Lloyd, M, Ashley, SE, Pitkin, S, Axelrad, C, et al
The Lancet. Child & adolescent health. 2022;(3):171-184
Abstract
BACKGROUND Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING National Health and Medical Research Council Australia and Prota Therapeutics.
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Osmotic demyelination syndrome improving after immune-modulating treatment: Case report and literature review.
Kalampokini, S, Artemiadis, A, Zis, P, Hadjihannas, L, Parpas, G, Kyrri, A, Hadjigeorgiou, GM
Clinical neurology and neurosurgery. 2021;:106811
Abstract
BACKGROUND Osmotic demyelination syndrome (ODS), which embraces central pontine and extrapontine myelinolysis, is an uncommon neurological disorder that occurs due to plasma osmotic changes. CASE PRESENTATION We present the case of a 55-year-old man, who presented with severe hyponatremia due to repeated vomiting, antidepressant treatment and consumption of large amounts of water. Fifteen days after sodium correction, the patient showed fluctuation of vigilance, dysarthria and dysphagia, tremor, cogwheel rigidity, bilateral facial palsy, ophthalmoplegia and tetraparesis. A brain MRI scan revealed extrapontine and later on pontine myelinolysis. He received intravenous steroids and subsequently immunoglobulin. His status began to improve gradually after completion of immunoglobulin and at three month-follow-up had no neurological deficit. LITERATURE REVIEW A comprehensive literature search of all reported ODS cases that received immunoglobulin, steroids or plasmapheresis was conducted in the electronic databases PubMed and Web of science. CONCLUSIONS Improvement was seen in most cases that received immunoglobulin either during treatment or in the first days after treatment. With regard to steroids, although most cases reported improvement in the following months their effect on the outcome is unclear. Most cases treated with plasmapheresis reported favorable outcome at variable follow-up time. Immunoglobulin and steroids have immunomodulatory effects, which could contribute to promotion of myelin repair in ODS. Plasmapheresis has effects on the immune system beyond removing myelinotoxins from the circulation. More evidence is required to support their use in ODS. However, in view of the disease severity, these therapeutic choices should be considered in the clinical management of ODS.
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The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.
Fiorino, S, Zippi, M, Gallo, C, Sifo, D, Sabbatani, S, Manfredi, R, Rasciti, E, Rasciti, L, Giampieri, E, Corazza, I, et al
The British journal of nutrition. 2021;(3):275-293
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Abstract
In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.
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Impact of phytochemicals and plant extracts on viability and proliferation of NK cell line NK-92 - a closer look at immunomodulatory properties of goji berries extract in human colon cancer cells.
Kwaśnik, P, Lemieszek, MK, Rzeski, W
Annals of agricultural and environmental medicine : AAEM. 2021;(2):291-299
Abstract
INTRODUCTION Due to the fact that lymphocytes NK (natural killer cells) are the first line of defence of the body against cancer, one of the goals of modern immunotherapy is the enhancement of their natural activities for the effective recognition, detection, and elimination of cancer cells. OBJECTIVE The aim of the study was to evaluate the influence of selected phytochemicals (curcumin and resveratrol) and plant extracts (chlorella and goji berries) on NK cells viability and proliferation, as well as cytotoxic activity against colon cancer - one of the most common cancer worldwide. MATERIAL AND METHODS The impact of phytochemicals, viability and proliferation of plant extracts on NK cells was examined in NK-92 cells using both LDH and MTT assays. The immunomodulatory properties of selected compounds were tested against human colon cancer cell line LS180 using the MTT test. RESULTS Extracts of chlorella and goji berries significantly increased NK cell proliferation, while curcumin and resveratrol did not affect this process. Curcumin, as well as extracts of chlorella and goji berries, did not impact NK viability, while resveratrol significantly increased it. LDH test revealed the cytotoxic effect of chlorella extract and curcumin in NK-92 cell cultures. On the contrary, goji berries extract significantly decreased LDH level, while resveratrol did not affect the integrity of NK cell membranes. Studies conducted in co-cultures NK cells, also directly eliminated colon cancer cells. CONCLUSIONS Performed studies revealed immunomodulatory properties of goji berries extract, which improved viability and proliferation of NK cells, and above all, significantly increased their ability to recognize and eliminate colon cancer cells.
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Probiotics-Derived Peptides and Their Immunomodulatory Molecules Can Play a Preventive Role Against Viral Diseases Including COVID-19.
Manna, S, Chowdhury, T, Chakraborty, R, Mandal, SM
Probiotics and antimicrobial proteins. 2021;(3):611-623
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Abstract
As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the "probiotics-derived lipopeptides" role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.
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Proportions of circulating transitional B cells associate with MRI activity in interferon beta-treated multiple sclerosis patients.
Mimpen, M, Damoiseaux, J, van Doorn, W, Rolf, L, Muris, AH, Hupperts, R, van Luijn, MM, Gerlach, O, Smolders, J
Journal of neuroimmunology. 2021;:577664
Abstract
B-cells contribute to MS pathogenesis. The association of circulating B-cell phenotypes with combined unique active lesions (CUA) on MRI at 48 weeks follow-up was investigated in 50 interferon beta-treated MS patients. Transitional B-cell proportions were lower in participants with CUA at week 0 and 48 [p = 0.004, p = 0.002]. A decrease in circulating anti-EBNA-1 IgG levels between week 0 and 48 associated with absence of CUA [p = 0.047], but not with B-cell profiles. In a multi-factor model for CUA-risk, transitional B-cell proportions contributed independent from NK/T-cell ratio, change in anti-EBNA-1 IgG, and vitamin D supplementation. Transitional B-cells may predict treatment response in MS.
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Immunomodulatory Effects of Medicinal Plants used for Vitiligo in Traditional Persian Medicine.
Ebrahimabadi, MH, Lamardi, SNS, Shirbeigi, L
Current drug discovery technologies. 2021;(2):160-178
Abstract
BACKGROUND Vitiligo is a hypopigmentation disorder that affects 1% of the world's population. Vitiligo causes white spots on the skin, mucous membranes, or white hair by destroying skin melanocytes. The pathogenesis of vitiligo is unknown but autoimmune, autocytotoxic, and neural mechanisms are suggested. According to the autoimmune theory, in people with vitiligo, immune cells invade and damage melanocytes. T cells are more commonly present in vitiligo patients' skin and remain in the lesion site, which is composed of CD8 and CD4 T cells. Many studies have been conducted on the presence and role of cytokines such as interleukins and interferongamma (IFN-γ) in the vitiligo process. AIM: This study aimed to introduce herbs effective against vitiligo from the perspective of Persian medicine and to investigate their possible therapeutic mechanisms with the possible effects of herbs on autoimmune mechanisms. METHODS For this purpose, keywords were used to extract data from Persian medicine textbooks, and then relevant scientific databases, including Google Scholar, PubMed, Web of Science, and Scopus were examined. RESULTS It was found that Persian medicine scholars used 50 different medicinal plants to treat and reduce the complications of vitiligo, and recent scientific studies have proven immune-regulating properties and reducing the effect of many of them on cytokines. CONCLUSION According to scientific evidence on immunomodulatory effects, new research into the effects of these plants on vitiligo can lead to the discovery of new drugs and approaches for treating this disease.
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Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response.
Geindreau, M, Ghiringhelli, F, Bruchard, M
International journal of molecular sciences. 2021;(9)
Abstract
During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.
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Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial.
Mazeraud, A, Gonçalves, B, Aegerter, P, Mancusi, L, Rieu, C, Bozza, F, Sylla, K, Siami, S, Sharshar, T
Trials. 2021;(1):170
Abstract
BACKGROUND As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19 ). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS. METHODS The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level. DISCUSSION The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity. TRIAL REGISTRATION EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580 . Registered on 17 April 2020.