Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model

Evaluation of the Coagulation Dysfunction in Multiple Sclerosis from the Perspective of IgG Antibodies against Thrombus-Related Components

The strong link between coagulation and inflammation has recently been investigated in multiple sclerosis (MS) in the light of coagulant serine proteases as pro-inflammatory mediators in MS animal models. Our work attempted to enlighten the role of IgG antibodies against the coagulant proteases and characterize their effects in MS pathology. Serum samples from 15 seropositive MS patients for IgG against factor(F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C were subjected to antibody purification, followed by in vitro stimulation of human astrocytes. Samples from fourteen healthy controls and eight negative MS patients for antibodies were also subjected to the same procedure as negative controls. The expression levels of the thrombin-activated receptor (PAR-1) and activated pro-inflammatory ERK1/2 kinases were analyzed by immunoblot to evaluate intracellular pathways triggered by these antibodies. PAR-1 and ERK1/2 were upregulated up to four-fold and 2.5-fold, respectively, after stimulation with anti-thrombin IgG fraction or fractions with multiple antibodies, compared to untreated cells. Conversely, no substantial alteration was observed when samples from negative patients for IgG and controls were applied. Thus, IgG against coagulation components might be pro-inflammatory molecules useful for prognosis, monitoring, and developing new therapeutic approaches for MS

Serum Reactive Antibodies against the N-Methyl-D-Aspartate Receptor NR2 Subunit—Could They Act as Potential Biomarkers?

Synaptic dysfunction and disrupted communication between neuronal and glial cells play an essential role in the underlying mechanisms of multiple sclerosis (MS). Earlier studies have revealed the importance of glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, in excitotoxicity, leading to abnormal synaptic transmission and damage of neurons. Our study aimed to determine whether antibodies to the NR2 subunit of NMDAR are detected in MS patients and evaluate the correlation between antibody presence and clinical outcome. Furthermore, our focus extended to examine a possible link between NR2 reactivity and anti-coagulant antibody levels as pro-inflammatory molecules associated with MS. A cross-sectional study was carried out, including 95 patients with MS and 61 age- and gender-matched healthy controls (HCs). The enzyme-linked immunosorbent assay was used to detect anti-NR2 antibodies in serum samples of participants along with IgG antibodies against factor (F)VIIa, thrombin, prothrombin, FXa, and plasmin. According to our results, significantly elevated levels of anti-NR2 antibodies were detected in MS patients compared to HCs (p < 0.05), and this holds true when we compared the Relapsing-Remitting MS course with HCs (p < 0.05). A monotonically increasing correlation was found between NR2 seropositivity and advanced disability (rs = 0.30; p < 0.01), anti-NR2 antibodies and disease worsening (rs = 0.24; p < 0.05), as well as between antibody activity against NR2 and thrombin (rs = 0.33; p < 0.01). The presence of anti-NR2 antibodies in MS patients was less associated with anti-plasmin IgG antibodies [OR:0.96 (95%CI: 0.92–0.99); p < 0.05]; however, such an association was not demonstrated when analyzing only RRMS patients. In view of our findings, NR2-reactive antibodies may play, paving the way for further research into their potential as biomarkers and therapeutic targets in MS

A Preclinical Investigation on the Role of IgG Antibodies against Coagulant Components in Multiple Sclerosis

The coagulation-inflammation interplay has recently been identified as a critical risk factor in the early onset of multiple sclerosis (MS), and antibodies against coagulation components have been recognized as contributing factors to thrombotic and inflammatory signaling pathways in diseases with overlapping symptoms to MS, paving the way for further research into their effects on MS pathology. The current study aimed to enlighten the role of IgG antibodies against coagulation components by performing a preclinical study, analyzing the astrocytic activation by purified IgG antibodies derived from 15 MS patients, and assessing their possible pro-inflammatory effects using a bead-based multiplexed immunoassay system. The results were compared with those obtained following astrocyte treatment with samples from 14 age- and gender-matched healthy donors, negative for IgG antibody presence. Serum samples collected from 167 MS patients and 40 age- and gender-matched controls were also analyzed for pro- and anti-inflammatory factors. According to our results, astrocytic activation in response to IgG treatment caused an upregulation of various pro-inflammatory factors, including cytokines, chemokines, and interleukins. Conversely, in serum samples from patients and controls, the pro-inflammatory factors did not differ significantly; medication may lower the levels in patients. Our findings suggest that antibodies may function as effectors in neuroinflammation and serve as targets for new treatments that eventually benefit novel therapeutic approaches

SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in individuals with multiple sclerosis receiving different disease-modifying treatments

IntroductionThe study aims to evaluate the concentration of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike1 protein (S1RBD) in BNT162b2- vaccinated relapsing-remitting multiple sclerosis (RRMS) individuals receiving disease-modifying treatments (DMTs).MethodsSerum from 126 RRMS volunteers was collected 3 months after the administration of the second dose of the Pfizer-BioNTech BNT162b2 vaccine. Additional samples were analyzed after the administration of the booster dose in fingolimod- treated MS. Anti-S1RBD IgG antibody concentrations were quantified using the ABBOTT SARS-CoV-2 IgG II Quant assay.ResultsAnti-S1RBD IgG antibody concentrations in RRMS individuals receiving natalizumab, interferons, teriflunomide, and dimethyl fumarate showed no significant difference to those in healthy controls. However, fingolimod-treated MS individuals showed a marked inability to produce SARS-CoV-2- specific antibodies (p &amp;lt; 0.0001). Furthermore, a booster dose was not able to elicit the production of IgG antibodies in a large portion of matched individuals.DiscussionA possible explanation for the altered immune response in fingolimod- treated MS individuals could be due to the medication inhibiting the circulation of lymphocytes, and possibly in turn inhibiting antibody production. Overall, patients on DMTs are generally of no disadvantage toward mounting an immune response against the vaccine. Nevertheless, further studies require evaluating non-humoral immunity against SARS-CoV-2 following vaccination, as well as the suitability of such vaccinations on patients treated with fingolimod.</jats:sec

Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) with an unknown etiology, although genetic, epigenetic, and environmental factors are thought to play a role. Recently, coagulation components have been shown to provide immunomodulatory and pro-inflammatory effects in the CNS, leading to neuroinflammation and neurodegeneration. The current study aimed to determine whether patients with MS exhibited an overrepresentation of polymorphisms implicated in the coagulation and whether such polymorphisms are associated with advanced disability and disease progression. The cardiovascular disease (CVD) strip assay was applied to 48 MS patients and 25 controls to analyze 11 genetic polymorphisms associated with thrombosis and CVD. According to our results, FXIIIVal34Leu heterozygosity was less frequent (OR: 0.35 (95% CI: 0.12&ndash;0.99); p = 0.04), whereas PAI-1 5G/5G homozygosity was more frequent in MS (OR: 6.33 (95% CI: 1.32&ndash;30.24); p = 0.016). In addition, carriers of the HPA-1a/1b were likely to have advanced disability (OR: 1.47 (95% CI: 1.03&ndash;2.18); p = 0.03) and disease worsening (OR: 1.42 (95% CI: 1.05&ndash;2.01); p = 0.02). The results of a sex-based analysis revealed that male HPA-1a/1b carriers were associated with advanced disability (OR: 3.04 (95% CI: 1.22&ndash;19.54); p = 0.01), whereas female carriers had an increased likelihood of disease worsening (OR: 1.56 (95% CI: 1.04&ndash;2.61); p = 0.03). Our findings suggest that MS may be linked to thrombophilia-related polymorphisms, which warrants further investigation

Characterization of IgG Antibody Response against SARS-CoV-2 (COVID-19) in the Cypriot Population

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, this study aimed to characterize the seroprevalence of SARS-CoV-2 antibodies in the Cypriot population for the first time since the pandemic started. Our results show that a majority of people infected with SARS-CoV-2 developed IgG antibodies against the virus, whether anti-NP, anti-S1RBD, or both, at least 20 days after their infection. Additionally, the percentage of people with at least one antibody against SARS-CoV-2 in the group of volunteers deemed SARS-CoV-2 negative via RT-PCR or who remain untested/undetermined (14.43%) is comparable to other reported percentages worldwide, ranging anywhere from 0.2% to 24%. We postulate that these percentages reflect the underreporting of true infections in the population, and also show the steady increase of herd immunity. Additionally, we showed a significantly marked decrease in anti-NP IgG antibodies in contrast to relatively stable levels of anti-S1RBD IgG antibodies in previously infected individuals across time.</jats:p

Characterization of IgG Antibody Response against SARS-CoV-2 (COVID-19) in the Cypriot Population

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, this study aimed to characterize the seroprevalence of SARS-CoV-2 antibodies in the Cypriot population for the first time since the pandemic started. Our results show that a majority of people infected with SARS-CoV-2 developed IgG antibodies against the virus, whether anti-NP, anti-S1RBD, or both, at least 20 days after their infection. Additionally, the percentage of people with at least one antibody against SARS-CoV-2 in the group of volunteers deemed SARS-CoV-2 negative via RT-PCR or who remain untested/undetermined (14.43%) is comparable to other reported percentages worldwide, ranging anywhere from 0.2% to 24%. We postulate that these percentages reflect the underreporting of true infections in the population, and also show the steady increase of herd immunity. Additionally, we showed a significantly marked decrease in anti-NP IgG antibodies in contrast to relatively stable levels of anti-S1RBD IgG antibodies in previously infected individuals across time

Conjugated linoleic acids (CLA) as precursors of a distinct family of PUFA

One of the possibilities for distinct actions of c9,t11- and the t10,c12-conjugated linoleic acid (CLA) isomers may be at the level of metabolism since the conjugated diene structure gives to CLA isomers and their metabolites a distinct pattern of incorporation into the lipid fraction and metabolism. In fact, CLA appears to undergo similar transformations as linoleic acid but with subtle isomer differences, which may account for their activity in lowering linoleic acid metabolites in those tissues rich in neutral lipids where CLA is preferentially incorporated. Furthermore, c9,t11 and t10,c12 isomers are metabolized at a different rate in the peroxisomes, where the shortened metabolite from t10,c12 is formed at a much higher proportion than the metabolite from c9,t11. This may account for the lower accumulation of t10,c12 isomer into cell lipids. CLA isomers may therefore be viewed as a \u201cnew\u201d family of polyunsaturated fatty acids (PUFA) producing a distinct range of metabolites using the same enzymatic system as the other (i.e., n 123, n 126 and n 129) PUFA families. It is likely that perturbation of PUFA metabolism by CLA will have an impact on eicosanoid formation and metabolism, closely linked to the biological activities attributed to CLA