November 10-15

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ACR Convergence 2023

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Home // Latest research into innate immune system disorders is changing thinking about autoinflammatory diseases

Latest research into innate immune system disorders is changing thinking about autoinflammatory diseases


3 minutes

Daniel L. Kastner, MD, PhD
Daniel L. Kastner, MD, PhD

Research on a range of inflammatory conditions has led to insights with far reaching practical implications that are changing the way rheumatologists think about autoinflammatory diseases. On Tuesday from 2:30 – 4:00 pm in Room W375a, the clinical practice session Adult Autoinflammatory Diseases will review the current data on disorders of the innate immune system and how to approach these conditions.

Daniel L. Kastner, MD, PhD, Scientific Director of the National Human Genome Research Institute, Bethesda, MD, will begin the session with a lecture titled, “The Adult With Undifferentiated Autoinflammatory Disease.”

“In rheumatology clinics across the country, we are sometimes confronted with patients who are referred to us with unexplained fever and inflammation without the high titer autoantibodies that we would see with something like lupus or rheumatoid arthritis,” Dr. Kastner said. “Do they have an autoinflammatory disease?”

Dr. Kastner will first review what steps rheumatologists should take in these scenarios to rule out such things as occult infection or occult malignancy.

“After you’ve considered those possibilities, there are sometimes still those situations where you don’t have a good explanation for why the patient has recurrent fever and inflammation,” he said. “They don’t have a classic autoimmune disease or the usual clinical manifestations of something like lupus.”

In such cases, autoinflammatory diseases should be considered, and research is revealing that even those that typically present in childhood may sometimes appear later in life. And now, Dr. Kastner can tell us how.

“I’ll discuss the different autoinflammatory diseases we can think about in adults. Adult-onset Still’s disease is certainly one that comes to mind,” he said. “But I’ll also discuss one of the interesting new developments in research on this topic — the fascinating possibility that some patients might have somatic mutations in disease genes that are the same ones we see as germline mutations in children. But here we’re seeing adults with somatic changes causing adult onset of diseases that are typically diagnosed in childhood and caused by germline mutations.”

Over the past five years, Dr. Kastner and other researchers have identified cases of adult-onset autoinflammatory diseases.

“These patients have a normal germline genome with regard to a particular gene that may cause an autoinflammatory disease,” he said. “But if you look just at a certain subpopulation of white blood cells, they have developed a somatic mutation in a particular autoinflammatory gene.”

An example is the NLRP3 gene, which is associated with cryopyrin-associated periodic syndromes, a spectrum of autoinflammatory conditions that usually present very early in life.

In one case, Dr. Kastner saw a patient who was healthy until her 40s, when she developed symptoms consistent with Muckle-Wells syndrome, which usually presents early in life and is caused by germline mutations in the NLRP3 gene.

“After an extensive analysis of the DNA sequence in her white blood cells, we found a mutation in that NLRP3 gene but only in 10 to 15 percent of her cells,” he said. “That was enough for her to develop this Muckle-Wells presentation, and she responded well to inhibitors of interleukin-1.”

These findings, he said, raise the question of how many people who present with unexplained recurrent fevers and inflammation later in life might have somatic mutations in these genes.

The session will include two other lectures. Apostolos Kontzias, MD, Associate Professor of Medicine and Rheumatology Fellowship Program Director at Stony Brook University School of Medicine, Stony Brook, NY, will present “Idiopathic Recurrent Pericarditis.” Polly Ferguson, MD, Professor of Pediatrics and Director of the Division of Pediatric Rheumatology at the University of Iowa Stead Family Children’s Hospital, Iowa City, IA, will discuss the pathophysiology, clinical presentation, and treatment of chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) in adults.