NIH Demystifying Medicine: Reimagining the Taxonomy of Autoinflammatory Disease

Immunocompromised? Autoimmune disease? Autoinflammatory disease? What’s the relationship? The next Demystifying Medicine explores these illnesses through the lens of conditions that present with painful mouth ulcers. These include an autoinflammatory disease called PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis), known as the “most periodic” of the periodic fever diseases, as well as Behçet’s disease, a new monogenic illness termed ‘HA20,’ and even common canker sores.

NIH scientists led by Drs. Kastner and Manthiram discovered variants in inflammation-related genes associated with PFAPA syndrome, which may lead to treatment for this condition mostly affecting children and characterized by episodic fever, oral ulcers, sore throat, and swollen lymph glands. In contrast, HA20 afflicts children of all ages; the gene was identified by Drs. Kastner, Schwartz, and their colleagues.

These genetic discoveries are also revealing deep insights into malfunction in the innate immune system, which may open new pathways to more broadly understand immunity gone awry in diseases such as lupus and rheumatoid arthritis.

Dr. Kastner is an NIH Distinguished Investigator and chief of the Inflammatory Disease Section in the NHGRI Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch. Dr. Manthiram is a newly appointed Assistant Clinical Investigator in the NIAID Cell Signaling and Immunity Section, having completed a fellowship in Dr. Kastner’s lab.

Dr. Schwartz is an Assistant Clinical Investigator in the NIAID Laboratory of Allergic Diseases, where she sees patient volunteers, investigates relationships between allergic inflammation and autoimmune problems, and has worked with Drs. Kastner and Manthiram on the riddle of autoinflammatory disorders.

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