Macrophage Activation in Follicular Conjunctivitis during the COVID-19 Pandemic

Among the symptoms of SARS-CoV-2, follicular conjunctivitis has become relevant. The conjunctiva acts as an open lymph node, reacting to the viral antigen that binds the epithelial cells, forming follicles of B cells with activated T cells and NK cells on its surface, which, in turn, talk to monocyte-derived inflammatory infected macrophages. Here, the NLRP3 inflammasome is a major driver in releasing pro-inflammatory factors such as IL-6 and caspase-1, leading to follicular conjunctivitis and bulbar congestion, even as isolated signs in the ‘asymptomatic’ patient

Vascular risk factors in glaucoma: the results of a national survey

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls

The role of gene therapy in the treatment of retinal diseases: A review

Background: Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. Objective: The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. Method: Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. Results: We present the available results of current active clinical trials for inherited retinal disease such as Leberâ\u80\u99s congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. Conclusion: Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies

Diagnosis of a Neonatal Ophthalmic Discharge, Ophthalmia Neonatorum, in the “Molecular Age”: Investigation for a Correct Therapy

An early double case of acute Ophthalmia neonatorum in 3-day-old twins is reported. Culture of eye swabs showed a wide bacterial polymorphism, in which common bacteria, such as Klebsiella pneumoniae, Streptococcus pneumoniae, Corynebacterium ulcerans and other Enterobacteriaceae, coexisted with atypical Mycoplasmataceae and Chlamydiaceae from resident cervical-vaginal maternal microbiota. The neonates were in an apparently healthy state, but showed red eyes with abundant greenish-yellow secretion, mild chemosis and lid edema. The maternal cervical-vaginal ecosystem resulted differently positive to the same common cultivable, atypical bacteria culturally and molecularly determined. This suggested a direct maternal-foetal transmission or a further foetal contamination before birth. An extended culture analysis for common bacteria to atypical ones was decisive to describe the involvement of Mycoplasmas (M. hominis and U. urealyticum) within the scenario of the Ophthalmia neonatorum in a Caucasian couple. The introduction of a routine PCR molecular analysis for Chlamydiaceae and N. gonorrhoeae allowed to establish which of these were present at birth, and contributed to determine the correct laboratory diagnosis and to define an adequate therapeutic protocol obtaining a complete resolution after one year for culture and atypical bacteria controls. This study suggests to improve the quality of laboratory diagnosis as unavoidable support to a correct clinical diagnosis and therapy, in a standardized modality both for swabbing and scraping, to check the new-born microbial programming starting in uterus, overtaking the \u93cultural age\u94 to the \u93molecular age\u94, and to revise the WHO guidelines of \u93SAFE Strategy\u94 for trachoma eye disease, transforming it into \u93SAFES Strategy\u94 where the \u93S\u94 letter is the acronym of \u93Sexual ecosystem and behavioural valuation/education\u94

Impact of mold on mast cell-cytokine immune response

Molds include all species of microscopic fungi, the spores of which are small molecules, ubiquitous, mostly found in soil with higher rainfall and high humidity, in the atmosphere of urban and rural settings and in decaying vegetation. They originate from pathogenic fungi and have a crucial role in inflammatory response, causing a broad range of diseases. Immune suppressed subjects may develop mycoses caused by opportunistic common pathogenic fungi. Mast cells (MCs) are immune cells involved in the pathophysiology of infected skin, lung, and organs, where there is an increase of angiogenesis. Airways fungi infections can induce allergic lung disease mediated by MCs and other immune cells. In addition, fungal infection may cause and/or aggravate asthma inflammation. Spores are able to navigate in the airways of the lung and can be recognized trough toll-like receptor (TLR) signaling by the innate immune cells including MCs. Activated MCs release preformed mediators including histamine, proteases (tryptase, chimase), pro-inflammatory cytokines/chemokines and they also generate arachidonic acid products. MCs activated by fungi provoke an increases of PGD2 levels and lead to hypersensitivity diseases which present signs such as irritation of the respiratory tract and eyes, recurrent sinusitis, bronchitis, cough and neurological manifestations including fatigue, nausea, headaches and brain fog. Therefore, fungi activate the innate immune response through the TLRs, leading to the release of myeloid differentiation factor 88 (MyD88) which, with a series of cascade reactions, induces the stimulation of AP-1 and NF-kB with subsequent activation of inflammatory IL-1 family members. Here, we report that fungi can activate MCs to secrete pro-inflammatory cytokines which may be inhibited by IL-37, a new anti-inflammatory IL-1 family member

Anaphylaxis is a rare reaction in COVID-19 vaccination

: Anaphylaxis is a severe multisystem reaction that occurs rapidly after the introduction of an antigen that would otherwise be a harmless substance. It is characterized by airway and respiratory problems, cardiovascular collapse, mucosal inflammation, and other complications, all severe symptoms that can cause death. IgE-dependent anaphylaxis involves mast cells (MCs) which are the main sources of biologically active mediators that contribute to the pathological and lethal phenomena that can occur in anaphylaxis. Antibody-mediated anaphylaxis can follow multiple pathways such as that mediated by MCs carrying the FcεRI receptor, which can be activated by very small amounts of antigen including a vaccine antigen and trigger an anaphylactic reaction. In addition, anaphylaxis can also be provoked by high concentrations of IgG antibodies that bind to the FcγR receptor present on basophils, neutrophils, macrophages and MCs. For this reason, the IgG concentration should be kept under control in vaccinations. Activation of MCs is a major cause of anaphylaxis, which requires immediate treatment with epinephrine to arrest severe lethal symptoms. MCs are activated through the antigen binding and cross-linking of IgE with release of mediators such as histamine, proteases, prostaglandins, leukotrienes and inflammatory cytokines. The release of these compounds causes nausea, vomiting, hives, wheezing, flushing, tachycardia, hypotension, laryngeal edema, and cardiovascular collapse. mRNA and viral vector vaccines have been cleared by the United States, Food and Drug Administration (FDA), generating hope of prevention and cure for COVID-19 around the world. Scientists advise against giving the vaccine to individuals who have had a previous history of anaphylaxis. The US Centers for Disease Control and Prevention (CDC) advises people with a previous history of any immediate allergic reaction to remain under observation for approximately 30 minutes after COVID-19 vaccination. To date, vaccines that prevent SARS-CoV-2 infection have not raised major concerns of severe allergic reactions, although, in some cases, pain and redness at the injection site and fever have occurred after administration of the vaccine. These reactions occur in the first 24-48 hours after vaccination. It has been reported that probable forms of anaphylaxis could also occur, especially in women approximately 40 years of age. But after tens of millions of vaccinations, only a few patients had this severe reaction with a low incidence. Anaphylactic and severe allergic reactions can also occur to any component of the vaccine including polysorbates and polyethylene glycol. To date, there is no precise information on allergic reactions to COVID-19 vaccines. Individuals with MCs and complement with higher activation than others may be at greater allergic risk. Moreover, the reactions called anaphylactoids, are those not mediated by IgE because they do not involve this antibody and can also occur in COVID-19 vaccination. These not-IgE-mediated reactions occur through direct activation of MCs and complement with tryptase production, but to a lesser extent than IgE-mediated anaphylaxis. However, at the moment it is not known exactly which component of the vaccine causes the allergic reaction and which vaccine causes the most side effects, including anaphylaxis. Thus, individuals who have a known allergy to any component of the vaccine should not be vaccinated. However, should an anaphylactic reaction occur, this requires immediate treatment with epinephrine to arrest severe lethal symptoms. In conclusion, the purpose of this editorial is to encourage the population to be vaccinated in order to extinguish this global pandemic that is afflicting the world population, and to reassure individuals that anaphylactic reactions do not occur with a higher incidence than other vaccinations

IL-33 mediates allergy through mast cell activation: Potential inhibitory effect of certain cytokines

Mast cells (MCs) are hematopoietic immune cells commonly found in adjacent to blood vessels in the lamina propria of airway mucosa. They are important in allergic reactions since the cross-linking of their surface high affinity receptor FceRI induces activation of these cells, and provokes the synthesis, degranulation and release of inflammatory mediators including arachidonic acid-derived eicosanoids (de novo synthesized), stored enzyme mediators, and inflammatory TH1 and TH2 cytokines, and chemokines. Interleukin (IL)-33 participates in innate and adaptive immunity and inflammation and, acting on CD34+ cells, causes MC differentiation and maturation. IL-33 is generated by activated immune cells, and activates MCs which degranulate and release pro-inflammatory mediators. IL-33 is very important in mediating allergic inflammation and can be induced by IL-1 beta. It is also called \u201calarmin\u201d and is an inflammatory cytokine IL-1 family member, expressed from mocytes and MCs, which binds its receptor ST2, provoking its release after cell damage. MC-derived allergic compounds in response to IL-33 is critical to innate type 2 immunity. IL-37 is expressed by immune and non-immune cells after pro-inflammatory stimulus. IL-37, an anti-inflammatory cytokine, binds IL-18Ra and suppresses pro-inflammatory IL-1 beta released by activated immune cells such as macrophages. Here, we hypothesize that pro-inflammatory IL-1 family member cytokines released by activated MCs, mediating inflammatory allergic phenomenon, can be suppressed by IL-37

Microglia and mast cells generate proinflammatory cytokines in the brain and worsen inflammatory state: Suppressor effect of IL-37

Brain microglia cells are responsible for recognizing foreign bodies and act by activating other immune cells. Microglia react against infectious agents that cross the blood-brain barrier and release pro-inflammatory cytokines including interleukin (IL)-1β, IL-33 and tumor necrosis factor (TNF). Mast cells (MCs) are immune cells also found in the brain meninges, in the perivascular spaces where they create a protective barrier and release pro-inflammatory compounds, such as IL-1β, IL-33 and TNF. IL-1β binds to the IL-1R1 receptor and activates a cascade of events that leads to the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activation of the immune system. IL-33 is a member of the IL-1 family expressed by several immune cells including microglia and MCs and is involved in innate and adaptive immunity. IL-33 is a pleiotropic cytokine which binds the receptor ST2 derived from TLR/IL-1R super family and is released after cellular damage (also called “alarmin”). These cytokines are responsible for a number of brain inflammatory disorders. Activated IL-1β in the brain stimulates microglia, MCs, and perivascular endothelial cells, mediating various inflammatory brain diseases. IL-37 also belongs to the IL-1 family and has the capacity to suppress IL-1β with an anti-inflammatory property. IL-37 deficiency could activate and enhance myeloid differentiation (MyD88) and p38-dependent protein-activated mitogenic kinase (MAPK) with an increase in IL-1β and IL-33 exacerbating neurological pathologies. In this article we report for the first time that microglia communicate and collaborate with MCs to produce pro-inflammatory cytokines that can be suppressed by IL-37 having a therapeutic potentiality

How to classify the covid-19 phenotype: a response from "the first soldier in the first trench" in Lombardy, north-western Italy

none7no[No abstract available]mixedGallenga C.E.; Contini C.; Tana M.; D'Eliseo D.; Giuliani A.L.; Di Virgilio F.; Paglia S.Gallenga, C. E.; Contini, C.; Tana, M.; D'Eliseo, D.; Giuliani, A. L.; Di Virgilio, F.; Paglia, S

New concepts in neuroinflammation: Mast cells pro-inflammatory and anti-inflammatory cytokine mediators

The activation of brain nociceptors and neurons may lead to neurogenic inflammation, an event that involves immune cells including mast cells (MCs). Microglia are similar to macrophages and secrete pro-inflammatory IL-1 family members and TNF. TNF is rapidly released (first 10 minutes from MC granules) and is subsequently secreted along with other pro-inflammatory cytokines with a new synthesis after several hours. MC-derived TNF is a very powerful pro-inflammatory cytokine which mediates sensitization of the meningeal nociceptors. Here, we report the involvement of MCs in neuroinflammation, the role of inflammatory cytokine IL-1 family members, and of TNF, as well as the potential inhibition of IL-37