Peter H. Schafer, Ying Ye, Lei Wu, Jolanta Kosek, Garth Ringheim, Zhihong Yang, Liangang Liu, Michael Thomas, Maria Palmisano, Rajesh Chopra
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.
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. WoodsRead 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.
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.
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.
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
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.