Virtual Blau Syndrome Research Panel

Join leading experts as they share the latest research on Blau syndrome. Each presentation will be followed by a Q&A. 

Dr. Ruth J. Napier

Assistant Professor

Molecular Microbiology and Immunology

Oregon Health & Science University

Principal Investigator, Research Microbiologist VA Portland Health Care System

TOPIC: A NOD2 T cells: New insights into the pathogenesis of Blau Syndrome

SUMMARY: How dysregulation of the microbial sensor NOD2 causes Blau syndrome remains unknown. Here we have found an unexpected role for NOD2 in suppressing pathogenic T cells that cause arthritis and uveitis. Our findings contribute to our understanding of the immunopathogenesis of Blau Syndrome and provide insight into new therapeutic options for patients.

Dr. Naotomo Kambe

Associate Professor

Department of Dermatology

Kyoto University Graduate School of Medicine

TOPIC: Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan

SUMMARY: In 2004, we had the opportunity to care for a 27-year-old Japanese man diagnosed with early-onset sarcoidosis (EOS) / Blau syndrome. Currently, we have confirmed 50 cases of Blau syndrome in Japan. Collected cases were almost evenly distributed by age through the 40s and decreased after age 50. About half of the cases of Blau syndrome had fever from relatively early timepoints in the disease course. In some patients, disease onset was recognized after BCG vaccination. Most patients who became blind were treated with non-biologics, whereas none of the patients treated with biologics from a young age were blind. (Matsuda T, Kambe N, et al. Ann Rheum Dis 2020;annrheumdis-2020-217320.)

Dr. Gregory D. Fairn

Associate Professor

Departments of Biochemistry and Surgery

University of Toronto

Keenan Research Centre for Biomedical Science

St. Michael's Hospital, Unity Health Toronto

TOPIC: Acylation of NOD2 controls its subcellular targeting and signaling

SUMMARY: We have discovered that the peptidoglycan sensor NOD2 requires the post-translation addition of fatty acids (acylation) to localize properly in the cell and transduce signals in response to peptidoglycan. We have also found that a large number of human NOD2 mutations associated with Crohn’s disease are inefficiently acylated thus explaining their loss-of-function phenotype. Conversely, the C495Y mutant associated Blau Syndrome displays hyper-acylation in the absence of peptidoglycan while stimulating inflammatory signaling.  Restoring the acylation levels of the NOD2 C495Y to baseline reduces the pro-inflammatory signaling in cells. Thus, manipulating the levels of NOD2 acylation could be beneficial for treating Blau Syndrome.

Jean-Marie Brusq

Senior Program Director - Head of Translational Pharmacology

Oncodesign Biotech Business Unit – France

TOPIC: Discovery of ODS-101, a RIPK2 inhibitor, for the treatment of inflammatory diseases, via Nodosome regulation.

SUMMARY: Strong genetic evidence directly link the NOD2-RIPK2 axis to Blau syndrome. We choose RIPK2 as the most tractable target in this pathway to inhibit the nodosome overactivation. Using our proprietary Nanocyclix® platform we discovered ODS-101 a highly potent and selective RIPK2 inhibitor with exquisite developability properties. While the IND enabling studies are ongoing we will provide a full description of this potential “fist-in-class” pre-clinical candidate which could represent a new therapeutic option for Blau syndrome patients.

Kourosh Ahmadzadeh

PhD student at the Rega Institute, KU Leuven, Belgium under the supervision of Prof. Dr. Carine Wouters, Prof. Dr. Patrick Matthys and Dr. Carlos Rosé

TOPIC: Study of granuloma and giant cell formation in Blau syndrome.

SUMMARY: Examining the process of giant cell and granuloma formation in autoinflammatory diseases with a focus on Blau syndrome, by using complementary and cutting-edge technologies, including live cell analysis, advanced flow cytometry, RNA sequencing and proteomics, with the aim of finding a better therapy for Blau patients.