Vitamin D, inflammation and immunity: review of literature and considerations on recent translational and clinical research developments

The most relevant and recent literature findings linking exposure to sunlight, Vitamin D (VD), inflammation and immune system in health and disease, are reviewed. Reduced sunlight exposure determined hypo-vitaminosis D to be common among patients or even healthy subjects, especially at higher latitudes. Numerous studies support the hypothesis that VD insufficiency could contribute to the higher autoimmune diseases incidence in the same geographic areas. In the present review, the ways in which VD was reported to influence immune system, contributing to organism homeostasis or disease development are addressed. In fact, some of the hormone activities were recognised to determine stimulation or inhibition of immune system components. Several diseases, where an association with VD deficiency was studied, are summarised. Finally, the rationale for optimization of substitutive/additive therapy with VD analogues and the last innovations regarding these drugs are mentioned

Correction: Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

[This corrects the article DOI: 10.1371/journal.pone.0166433.]

Vitamin D deficiency and clinical correlations in systemic sclerosis patients: A retrospective analysis for possible future developments.

Objective Assessment of serum 25-hydroxyvitamin D (25(OH)D) correlations with clinical parameters and evaluation of the efficacy of standard oral supplementation in systemic sclerosis (SSc) patients. Methods 154 SSc patients were recruited, in all seasons. Serum 25(OH)D concentrations were evaluated using LIAISON 25-OH (Diasorin, Italy). Medsger disease severity scale (DSS), nailfold videocapillaroscopy (NVC) and all instrumental exam contemplated by international guidelines were performed. Drug assumption, including oral colecalciferol, was evaluated. Nonparametric tests were used for statistical analysis. Results Average 25(OH)D serum concentration was 18.7 \ub19 ng/ml (<20 classified as deficiency). A significant correlation was found with presence/absence of lung bi-basal fibrotic changes (16.1 \ub18 ng/ml and 20 \ub110 ng/ml, respectively; p = 0.04). Peripheral vascular (p = 0.03), kidney (p = 0.02), gastrointestinal (p = 0.05) Medsger\u2019s DSS parameters were found to correlate with 25(OH)D serum concentrations. No significant correlations were observed with digital ulcers incidence, strictly correlated to patterns of microangiopathy, defined at NVC analysis (p<0.0001). Interestingly, no effects of treatment with oral colecalciferol (Dibase 1,000 IU daily for at least 6 months) were found on 25(OH)D serum concentrations in treated (18.8 \ub110 ng/ml) or untreated (18.7 \ub19 ng/ml) SSc patients (p = 0.81). A significant difference was observed among seasonal 25(OH)D serum concentrations (winter: 14.6 \ub17.8 ng/ ml, spring: 17.2 \ub17.9 ng/ml, summer: 21.43 \ub110 ng/ml, autumn: 20.2 \ub110 ng/ml; p = 0.032) in all patients. Conclusion Serum 25(OH)D deficiency was found to correlate with lung involvement, peripheral vascular, kidney and gastrointestinal Medsger\u2019s DSS parameters and with seasonality In SSc patients. Supplementation with oral colecalciferol was found not effective in increasing 25 (OH)D serum concentrations. Therefore, for successful replacement, supra-physiological vitamin D3 doses or programmed UVB light exposure should be tested

Effectiveness of Immunoglobulin Replacement Therapy on Clinical Outcome in Patients with Primary Antibody Deficiencies: Results from a Multicenter Prospective Cohort Study

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Phenotype of BTK‐lacking myeloid cells during prolonged COVID‐19 and upon convalescent plasma

© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “Apoio Especial Research4COVID-19,” project numbers 125 and 803. André M. C. Gomes and Guilherme B. Farias received Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag Farmacêutica, respectively.info:eu-repo/semantics/publishedVersio

Acute HIV-1 and SARS-CoV-2 infections Share Slan+ Monocyte Depletion - evidence from an hyperacute HIV-1 case report

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “Apoio Especial Research4COVID-19”, project numbers 125 to S.M.F. and 803 to A.C.T. Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag Farmacêutica were received by A.M.C.G. and G.B.F., respectively.info:eu-repo/semantics/publishedVersio

Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype

Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.The Research was funded by Fundação para a Ciência e Tecnologia (FCT), “APOIO ESPECIAL RESEARCH 4COVID-19” projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACÊUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667824.info:eu-repo/semantics/publishedVersio

SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection. COVID-19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10+ ILC2 emerge as relevant contributors to SARS-CoV-2 pneumonia recovery.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “APOIO ESPECIAL RESEARCH4COVID-19,” project numbers 125 to SMF and 803 to ACT. AMCG and GBF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD) and JANSSEN- CILAG FARMACÊUTICA, respectively.info:eu-repo/semantics/publishedVersio

An external quality assessment feasibility study; cross laboratory comparison of haemagglutination inhibition assay and microneutralization assay performance for seasonal influenza serology testing: A FLUCOP study

Introduction: External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods. Methods: We invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays. Results: Within run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization. Discussion: This study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.publishedVersio

Novel Textbook Outcomes following emergency laparotomy:Delphi exercise

Background: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. Methods: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1–5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. Results: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into ‘early’ and ‘longer-term’. For non-trauma patients the proposed early Textbook Outcome was ‘Discharged from hospital without serious postoperative complications (Clavien–Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was ‘Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien–Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)’. The longer-term Textbook Outcome for both non-trauma and trauma was ‘Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year’. Conclusion: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.</p