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

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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.

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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

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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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Carbon nanotubes and nanofibers exposure and sputum and blood biomarkers of early effect among U.S. workers

Carbon nanotubes and nanofibers are used in many fields, such as in manufacturing and information technology. Both of these carbon particles are physically similar to asbestos, and one type of carbon nanotube (MWCNT-7) have recently been found to be carcinogenic. Due to the variety of carbon nanotubes and nanofibers, accessing their potential toxicity to workers remains difficult. Animal studies have demonstrated that exposure to nanotubes and nanofibers can lead to oxidative stress and cardiovascular effects locally and systemically. This is the first industrywide cross-sectional study across 12 different sites in the United States. Of the 144 workers identified, 108 workers from 12 different companies provided blood and/or sputum samples. Using a custom biomarker panel, Myriad RBM analyzed collected sputum and blood samples for 30 and 31 biomarkers respectively. Primary pattern identification used exploratory factor analyses with varimax rotation.
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Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS

Nirupama Putcha, Gabriel G. Paul, Antoine Azar, Robert A. Wise, Wanda K. O’Neal, Mark T. Dransfield, Prescott G. Woodruff, Jeffrey L. Curtis, Alejandro P. Comellas, M. Bradley Drummond, Allison A. Lambert, Laura M. Paulin, Ashraf Fawzy, Richard E. Kanner, Robert Paine, III, MeiLan K. Han, Fernando J. Martinez, Russell P. Bowler, R. Graham Barr, Nadia N. Hansel, for the SPIROMICS investigators
Read Full Article » Chronic obstructive pulmonary disease (COPD) is a leading cause of death, not just in the US but also worldwide. Patients with COPD are at increased risk for various respiratory infections, which are main contributors to COPD exacerbations. Selective IgA deficiency is associated with higher risk of respiratory infections, however, a link between serum IgA levels and COPD disease activity has never been established. The goal of this study is to test the hypothesis that sub serum IgA levels is associated with increased morbidity in COPD patients, using participants from the SPIROMICS cohort. Serum was collected at enrollment, and IgA levels were measured using the Myriad RBM biomarker discovery platform. Deficient IgA was defined as <7mg/dL and subnormal level defined as ≤70mg/dL. Follow-up was conducted yearly at the clinic and quarterly by phone for up to 3 years.
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