Serum Kidney Injury Molecule 1 and β2-Microglobulin Perform as well as Larger Biomarker Panels for Prediction of Rapid Decline in Renal Function in Type 2 Diabetes

The goal of this study is to determine if biomarkers can be used to be predictive of renal disease progression in diabetes as a method to enrich clinical trials with patients most at risk. From the SUMMIT (Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools) programme, the authors originally identified 207 serum biomarkers that is predictive of renal function decline. From these 207 biomarkers, the authors selected 42 biomarkers using forward selection and least absolute shrinkage and selection operator (LASSO) penalized regression approaches. The 42 biomarkers were split into smaller panels and tested for the ability to predict performance similar to the larger panels.

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Association between Cytokines and Functional, Hemodynamic Parameters, and Clinical Outcomes in Pulmonary Arterial Hypertension

Aditya A. Joshi, Ryan Davey, Youlan Rao, Kai Shen, Raymond L. Benza, Amresh Raina

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Pulmonary arterial hypertension (PAH) is a result of changes in the distal pulmonary vasculature that can lead to progressive debilitating symptoms and often result in death. While smooth muscle cell proliferation, endothelial dysfunction, and vascular inflammation are all believed to play important roles in PAH, but recently, more attention has been focused on inflammation mechanisms. Emerging evidence suggests that there may be circulating factors that can serve as biomarkers to monitor disease progression and treatment response. This study used patients enrolled in two clinical trials that were treated with treprostinil (TRUST-1 and FREEDOM-C2). Plasma was collected at baseline and at 12 or 16 week follow up and analyzed using DiscoveryMAP at Myriad RBM.

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Pulmonary Inflammation in Patients with Chronic Obstructive Pulmonary Disease with Higher Blood Eosinophil Counts

Patients with chronic obstructive pulmonary disease (COPD) exhibiting high eosinophils in sputum and blood have a better response to inhaled corticosteroid intervention. In a letter to the editor, Kolsum et al characterized the inflammatory profile of COPD patients comparing those with high (>250 cells/μL) versus low (<150 cells/μL) blood eosinophil numbers. Using Myriad RBM’s custom MAP technology, 102 inflammatory proteins related to pulmonary inflammation were measured in serum, sputum, and BAL (bronchial alveolar lavage).
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Cereblon modulator iberdomide induces degradation of the transcription factors Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus

Peter H. Schafer, Ying Ye, Lei Wu, Jolanta Kosek, Garth Ringheim, Zhihong Yang, Liangang Liu, Michael Thomas, Maria Palmisano, Rajesh Chopra
Read Full Article » Ikaros and Aiolos regulate homeostasis and leukocyte development. Ikaros is expressed in haematopoietic precursors and affects both B and T cell development. Aiolos is only found in pre-B cells and mature peripheral B cells and is necessary for long-lived plasma cells. Polymorphisms in their respective genes (IKZF1 and IKZF3 loci) have been reported to correlate with increased risk for systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by production of autoantibodies. Iberdomide (CC-220) is an oral compound being investigated for treatment of SLE. CC-220 is a high-affinity ligand of cereblon and upon binding leads to degradation of cereblon substrates, Ikaros and Aiolos. The degradation of Ikaros and Aiolos increases T cell production of IL-2, demonstrating potential immune modulatory effects.
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Networks of blood proteins in the neuroimmunology of schizophrenia

Clark D. Jeffries, Diana O. Perkins, Margot Fournier, Kim Q. Do, Michel Cuenod, Ines Khadimallah, Enrico Domenici, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Daniel H. Mathalon, Thomas H. McGlashan, Larry J. Seidman, Ming Tsuang, Elaine F. Walker, and Scott W. Woods
Read Full Article » Schizophrenia patients often present with changes in circulating immune proteins, which can cross the blood-brain barrier (BBB) and directly affect brain function. Many studies have hypothesized that psychosis is related to a dysregulation in the peripheral immune system that leads to abnormal signaling in the BBB. Patients defined as high-risk are 100 times more likely to develop a psychotic disorder within 2 years of diagnosis, and being able to predict progression to psychosis can be a useful tool for early intervention and improve clinical outcomes.
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IL-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses

Leonieke J.J. van Mens, Marleen G.H. van de Sande, Silvia Menegatti, Sija Chen, Iris C.J. Blijdorp, Henriette M. de Jong, Inka A. Fluri, Talia E. Latuhihin, Arno W.R. van Kuijk, Lars Rogge, Nataliya G. Yeremenko, Dominique L.P. Baeten.
Read Full Article » Therapeutic options beyond TNF inhibition for psoriasis, psoriatic arthritis, and ankylosing spondylitis are narrowing towards the IL-17 cytokine pathway. Indeed, in psoriatic arthritis, IL-17A blocker has demonstrated superior efficacy compared to the TNF inhibitors. Spondyloarthritis, which covers both ankylosing spondylitis and psoriatic arthritis diseases, has not been well studied in regards to the IL-17 blocker, secukinumab. This study, sponsored by Novartis Pharma, examined the effect of secukinumab on immunopathology of the synovial membrane and systematic immune responses.
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Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study

Martin Andersen, Mikael Boesen, Karen Ellegaard, Kalle Söderström, Niels H. Søe, Pieter Spee, Ulrik G. W. Mørch, Søren Torp-Pedersen, Else M. Bartels, Bente Danneskiold-Samsøe, Lars Karlsson, Henning Bliddal
Read Full Article » The use of biologic disease modifying anti-rheumatic drugs (bDMARDs) significantly changed the treatment of rheumatoid arthritis (RA), however only 15 percent of these patients ever achieve remission. Thus, predicting patient responses to treatment and achieving disease control remains great challenges in RA. One possible solution put forth by the authors is the use of explants, in vitro culturing, of synovial tissue. This study examined the effects of bDMARDs on baseline RA synovial explants production of IL-6 with each individual’s clinical response to the same bDMARDs.
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