Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis Posted on May 23, 2023 by admin

https://www.science.org/doi/10.1126/sciadv.adg3032

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CYP24A1 gene variant rs2762943 is associated with low serum 1,25-dihydroxyvitamin D levels in multiple sclerosis patients Posted on May 15, 2023 by admin

Abstract

Background: Vitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. We recently identified a polymorphism in the CYP24A1 gene, rs2762943, that was associated with an increased MS risk. CYP24A1 encodes a protein involved in the catabolism of the active form of vitamin D. We investigated the immunological effects of carrying the rs2762943 risk allele, and its role as genetic modifier.
Methods: Serum levels of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in a cohort of 167 MS patients. In a subgroup of patients, expression levels of MHC class II and co-stimulatory molecules were determined by flow cytometry, and serum levels of proinflammatory (IFNG, GM-CSF, CXCL13) and anti-inflammatory (IL-10) cytokines and neurofilament light chain were measured by single-molecule array assays. The effect of the rs2762943 polymorphism on disease activity and disability measures was evaluated in 340 MS patients.
Results: Compared to non-carriers, carriers of the rs2762943 risk allele were characterized by reduced levels of 1,25(OH)2 D (p=0.0001), and elevated levels of IFNG (p=0.03) and GM-CSF (p=0.008), whereas no significant differences were observed for the other markers. The presence of the rs2762943 risk allele had no significant impact on disease activity and disability outcomes during follow-up. However, risk allele carriers were younger at disease onset (p=0.04).
Conclusions: These findings suggest that the CYP24A1 rs2762943 polymorphism plays a more important role on MS susceptibility than on disease prognosis, and is associated with lower 1,25(OH)2 D levels and heightened pro-inflammatory environment in MS patients.

Malhotra S, Midaglia L, Chuquisana O, Patsopoulos NA, Ferrer R, Giralt M, Fissolo N, Gil-Varea E, Triviño JC, Lünemann JD, Montalban X, Comabella M. The CYP24A1 gene variant rs2762943 is associated with low serum 1,25-dihydroxyvitamin D levels in multiple sclerosis patients. Eur J Neurol. 2023 May 14. doi: 10.1111/ene.15866. Epub ahead of print. PMID: 37183562.

https://pubmed.ncbi.nlm.nih.gov/37183562/

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Serological response to vaccination in post-acute sequelae of COVID Posted on May 4, 2023 by admin

Abstract

Background

Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC.

Methods

We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity.

Results

Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden.

Conclusion

We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Joung, S., Weber, B., Wu, M. et al. Serological response to vaccination in post-acute sequelae of COVID.BMC Infect Dis 23, 97 (2023). https://doi.org/10.1186/s12879-023-08060-y

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08060-y

 

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Modulation of the sigma-1 receptor pathway may be beneficial in preclinical models of inflammation and sepsis Posted on May 3, 2023 by admin

Rosen DA, Seki SM, Fernández-Castañeda A, Beiter RM, Eccles JD, Woodfolk JA, Gaultier A. Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci Transl Med. 2019 Feb 6;11(478):eaau5266. doi: 10.1126/scitranslmed.aau5266. Erratum in: Sci Transl Med. 2019 Mar 27;11(485): PMID: 30728287; PMCID: PMC6936250

https://pubmed.ncbi.nlm.nih.gov/30728287/

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Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders Posted on May 3, 2023 by admin

https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.20230078

Miller AH and Binder EB: Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders
Published Online:1 Apr 2023  https://doi.org/10.1176/appi.ajp.20230078

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Deciphering words and sentences from brain scans Posted on May 2, 2023 by admin

https://www.science.org/content/article/scientists-use-ai-decipher-words-and-sentences-brain-scans

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Pyramidal neurons form active, transient multilayered circuits perturbed by autism-associated mutations Posted on April 29, 2023 by admin

https://www.cell.com/cell/pdf/S0092-8674(23)00299-4.pdf

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Prevalence, Patterns, and Clinical Severity of Long COVID among Chinese Medicine Telemedicine Service Users: Preliminary Results from a Cross-Sectional Study Posted on April 20, 2023 by admin

Introduction: The emergence and persistence of symptoms after acute COVID-19 is expected to become a major burden on healthcare systems. We assessed the features of the post-COVID-19 Syndrome (Long COVID) burden in a cohort of COVID-19 patients during the fifth major wave in Hong Kong. Methods: A cross-sectional study of 135 patients with confirmed COVID-19 from Feb to Apr 2022 who utilized traditional Chinese medicine telemedicine services was conducted. The COVID-19 Yorkshire Rehabilitation Scale was administered using an online survey 12 weeks after the COVID-19 infection. Prevalence of symptom severity and functional impairments were assessed to identify burdens and patterns. The correlation between symptom severity, functional impairments, patient characteristics, and overall health was evaluated. Results: The mean age was 46.8 years, with 46 (34.1%) males. Symptoms, functional impairments, and overall health worsened significantly when compared to the status prior to the infection. More than 50% reported the following sequelae 12 weeks after the acute infection: breathlessness, laryngeal or airway complications, fatigue, weakness, sleep, cognition, and anxiety. The presence of a single symptom or functional impairment significantly correlated with at least seven other problems positively, except for pain. Severity tended to be higher among vulnerable groups, including those who were chronic disease patients, older, less well educated, female, or had incomplete COVID-19 vaccinations. Conclusions: Long COVID is a significant healthcare burden among telemedicine users in Hong Kong, with complex needs for symptom and functional impairment management. Designing relevant health and rehabilitation services tailored to the needs of these patients is warranted.

Fai Fai Ho et al.: Prevalence, Patterns, and Clinical Severity of Long COVID among Chinese Medicine Telemedicine Service Users: Preliminary Results from a Cross-Sectional Study. Int. J. Environ. Res. Public Health 20(3): 1827 (2023).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914360/

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SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges- Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19 Posted on April 18, 2023 by admin

https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1.full.pdf

 

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Considerations on gradual glutamate accumulation related to cognitive task performance Posted on April 13, 2023 by admin

Abstract: “Long-lasting activities with high demand in cognitive control are known to result in cognitive fatigue. However, the reason for control cost inflation remains elusive. A neurometabolic account was proposed in a recent study combining magnetic resonance spectroscopy (MRS) with daylong execution of behavioral tasks. It suggests that control cost during high-demand work is related to the necessity of recycling potentially toxic substances, specifically glutamate, which may accumulate extracellularly. As MRS provides estimates of metabolite concentrations, further evaluations are possible how well this hypothesis fits with fundamental consequences from the dynamic equilibrium of intercompartmental glutamate distributions.”

Möller HE. Considerations on gradual glutamate accumulation related to cognitive task performance. J Cereb Blood Flow Metab. 2023 Mar;43(3):476-478. doi: 10.1177/0271678X221139550. Epub 2022 Nov 11. PMID: 36369737; PMCID: PMC9941861.

https://pubmed.ncbi.nlm.nih.gov/36369737/

 

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