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).
Read More

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.
Read More

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.
Read More

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.
Read More

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.
Read More

S100A12 and S100A8/9 Proteins are Biomarkers of Articular Disease Activity in Blau Syndrome

Lin Wang, Carlos D. Rosé, Kevin P. Foley, Jordi Anton, Brigitte Bader-Meunier, Philippe Brissaud, Gaelle Chédeville, Rolando Cimaz, Jorge Fernández-Martin, Catherin Guly, Eric Hachulla, Miroslav Harjacek, Friederike Mackensen, Rosa Merino, Consuelo Modesto, Antonio Naranjo Hernández, Christine Pajot, Athimalaipet V. Ramanan, Akaluck Thatayatikom, Caroline Thomée, Sebastiaan Vastert, Bart J. Votta, John Bertin, and Carin H. Wouters.
Rheumatology 2018 Read Full Article » Blau syndrome is an inherited auto-inflammatory disease that is characterized by arthritis, dermatitis, and uveitis. Patients also experience the presence of non-caseating granulomas, suggesting that the disease pathogenesis involves activated macrophages. The current management of Blau disease, using familiar drug classes such as corticosteroids, DMARDS and biologics, is not adequate. In order to assist in future drug development studies, biomarkers for Blau disease activity will be extremely useful. Phagocyte specific S100 proteins, such as S100A12, S100A8, and S100A9, have been proposed as biomarkers for Blau syndrome. These proteins are secreted by neutrophils and macrophages upon activation. This prospective cohort study will aim to correlate disease activity with inflammatory and S100 proteins.
Read More

Phase I Clinical Results from FR104, a mAb Specific to CD28

Researchers led by Bernard Vanove of OSE Immunotherapeutics report in the December 7, 2016 issue of the Journal of Immunology on the first-in-human study of FR1041. OSE and collaborators at the University of Nantes and Janssen conducted a detailed phase I evaluation of safety, pharmacokinetics, pharmacodynamics and potency of FR104 in healthy volunteers.

Read More
1 2