Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses: Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses

International audienceExciting times for the field of renal autoimmune diseases have begun. In 2021, for the first time, two new drugs belimumab (1) and voclosporin ( 2) are approved for the treatment of lupus nephritis (LN) (1, 2). Other novel targeted therapies demonstrate clinical efficacy in large, randomized trials, such as avacopan for ANCA-associated vasculitis (AAV) (3), imlifidase for Goodpasture’s disease and iptacopan for IgA nephropathy (IgAN). Pathogenic molecules are specifically targeted by new drugs that help to uncover novel aspects of disease mechanisms leading to glomerulonephritis. Simultaneously, the field is boosted by novel big data technologies on the single cell levels such as high-sensitive multi-color flow cytometry, single-cell genomics (single-cell RNA sequencing - scRNAseq), single cell metabolomics and proteomics. The novel treatment options in renal autoimmune diseases almost simultaneously require new immunomonitoring tools. ‘Immunomonitoring’includes the wide range of approaches to monitoring immune responses by the cellular immune system (e.g. T-cells, B-cells, plasma cells, dendritic cells, neutrophils etc.), or by the humoral immune system (e.g. cytokines, (auto-)antibodies, urinary markers, etc.). Monitoring relevant immune responses in patients with renal autoimmune diseases helps us to better understand a) the underpinning immunological pathophysiology of these diseases; b) the beneficial effects of novel treatments on autoimmunity; and c) can potentially help doctors and patients guide a personalized treatment strategy, adding information on immunological (non-)response to a clinical (non-) response treatment and on disease prognosis. In the present Research Topic, we have been able to collect for you a vast amount of research addressing novel ways and the roleof immunomonitoring in the broad range of renal autoimmune disease including LN, AAV, IgAN, idiopathic membranous nephropathy (iMN) and complement-mediated disease (CMD)

Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses

International audienceAlternative strategies targeting dysregulated cytokine balance could be considered for these patients at high risk of relapse

Only Follow-up of Memory B Cells Helps Monitor Rituximab Administration to Patients with NeuroMyelitis Optica Spectrum Disorders

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-018-0101-4">https://link.springer.com/article/10.1007/s40120-018-0101-4</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence

International audienceIntroduction: Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level <2 μg/ml at month-3) is a risk factor for treatment failure. We developed a machine learning algorithm to predict the risk of underdosing based on patients’ characteristics at rituximab infusion. We investigated the relationship between the predicted risk of underdosing and the cumulative dose of rituximab required to achieve remission.Methods: Rituximab concentrations were measured at month-3 in 92 sera from adult patients with primary membranous nephropathy, split into a training (75%) and a testing set (25%). A forward-backward machine-learning procedure determined the best combination of variables to predict rituximab underdosing in the training data set, which was tested in the test set. The performances were evaluated for accuracy, sensitivity, and specificity in 10-fold cross-validation training and test sets.Results: The best variables combination to predict rituximab underdosing included age, gender, body surface area (BSA), anti-phospholipase A2 receptor type 1 (anti-PLA2R1) antibody titer on day-0, serum albumin on day-0 and day-15, and serum creatinine on day-0 and day-15. The accuracy, sensitivity, and specificity were respectively 79.4%, 78.7%, and 81.0% (training data set), and 79.2%, 84.6% and 72.7% (testing data set). In both sets, the algorithm performed significantly better than chance (P < 0.05). Patients with an initial high probability of underdosing experienced a longer time to remission with higher rituximab cumulative doses required to achieved remission.Conclusion: This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy

International audienceThe phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis

Image_2_Low baseline IFN-γ response could predict hospitalization in COVID-19 patients.jpeg

The SARS-CoV-2 infection has spread rapidly around the world causing millions of deaths. Several treatments can reduce mortality and hospitalization. However, their efficacy depends on the choice of the molecule and the precise timing of its administration to ensure viral clearance and avoid a deleterious inflammatory response. Here, we investigated IFN-γ, assessed by a functional immunoassay, as a predictive biomarker for the risk of hospitalization at an early stage of infection or within one month prior to infection. Individuals with IFN-γ levels below 15 IU/mL were 6.57-times more likely to be hospitalized than those with higher values (p65 years, and no vaccination were independently associated with hospitalization. In addition, we found a significant inverse correlation between low IFN-γ response and high level of IL-6 in plasma (Spearman’s rho=-0.38, p=0.003). Early analysis of the IFN-γ response in a contact or recently infected subject with SARS-CoV-2 could predict hospitalization and thus help the clinician to choose the appropriate treatment avoiding severe forms of infection and hospitalization.</p

A multinational Delphi consensus to end the COVID-19 public health threat

Despite notable scientific and medical advances, broader political, socioeconomic, and behavioural factors continue to undercut the response to the coronavirus disease 2019 (COVID-19) pandemic1,2. This Delphi study convened a diverse, multidisciplinary panel of 386 academic, health, NGO, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global public health threat. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry, and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of ragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust, and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by organisations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help bring this public health threat to an end

A multinational Delphi consensus to end the COVID-19 public health threat

Abstract Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches 1 , while maintaining proven prevention measures using a vaccines-plus approach 2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities 3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end