In this episode, I interview the NIH team who brought you VEXAS! Hear different points of view of this disease, how it was discovered, clinical presentations, as well as where this research could lead. Then, we wrap up with Dr. Kastner’s historical take on autoinflammatory disorders!

• Intro :11
• In this episode :12
• Big thanks to Peter Grayson, MD, MSc 2:07
• About our guests 2:30
• The interview 5:10
• How did VEXAS come about? 5:37
• You had an idea of where to start looking? 6:58
• What should rheumatologists know about ‘somatic mutation’? 12:31
• Do you think this could be a clue to other conditions? 13:37
• Can you tell us about some of the unique aspects that we see in these patients with MDS that make them atypical? 17:14
• How’s the clinician going to see or note the vacuoles? 18:53
• Do we have kind of a pathway for how the vacuoles are forming based on what we know about ubiquitization or is that unclear? 20:51
• What’s going to raise the antenna that this isn’t “run of the mill x disease”? 23:33
• How, in your experience, have patients responded to diagnoses being changed? 37:15
• Where does everyone see the therapy going for this condition in the future? 41:15
• Do we think that with this approach that this is going to “reshuffle the deck” of what we call certain diseases from multiple different specialties over the next decade? 44:02
• Would you mind walking us through a little bit about FMF and how the different variants you saw led to further discoveries? 49:46
• What was known about IL1 at the time? How did that knowledge of IL1 come along? 52:53
• It’s such a true honor to have you all on 57:42

David Beck, MD, PhD, is a genetics fellow at the NIH. He can be reached at [email protected].

Marcella A. Ferrada, MD, is Lawrence Shulman scholar at NIAMS. She can be reached at [email protected].

Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and associate director of the NIAMS fellowship program. He can be reached at [email protected].

Dan Kastner, MD, PhD, is an NIH distinguished investigator in the Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch; director in the Division of Intramural Research; and head of the Inflammatory Skin Disease Section at the National Human Genome Research Institute.

We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

Disclosures: Beck, Brown, Ferrada, Grayson and Kastner report no relevant financial disclosures.