In this episode, the hosts interview Prof Helen Lachmann about autoinflammatory syndromes, discussing their presentation, diagnosis, and treatment. They also cover diverse symptoms and the use of IL-1 blockade as a treatment option. The chapter on AA amyloidosis explores its causes, management, and prevention. Acquired autoinflammatory diseases in adults and the relationship between somatic mosaicism and critical gene changes are also discussed. The hosts express gratitude and bid farewell to the listeners for the year.
Autoinflammatory diseases are characterized by the overproduction of inflammatory cytokines and represent disorders of innate immune system overactivation.
AA amyloidosis, a major complication of auto-inflammatory diseases, can be entirely prevented by effectively treating the underlying chronic inflammatory disease.
Deep dives
Auto-inflammatory diseases are disorders of innate immunity
Auto-inflammatory diseases are defined as disorders of innate immunity that involve upregulation of the innate immune response, driven by neutrophil and monocyte activation of macrophages. These diseases are distinct from classic autoimmune diseases and are characterized by the overproduction of inflammatory cytokines. Auto-inflammatory diseases were initially recognized in the 20th century, and while most are genetic, there are also acquired forms of these diseases. The understanding of auto-inflammatory diseases has evolved, recognizing a spectrum between innate and acquired immunity, with auto-inflammatory diseases representing disorders of innate immune system overactivation.
Clinical presentation and diagnosis of auto-inflammatory diseases
Auto-inflammatory diseases often present with recurrent episodes of systemic inflammation, such as fever, occurring from an early age. The presentation can vary depending on the age group, with children potentially presenting with symptoms resembling recurrent infections, while adults may go undiagnosed for many years. These diseases can present to various specialties, including infectious diseases, dermatology, rheumatology, and even dentistry. Blood tests during episodes often show elevated markers of acute inflammation, such as C-reactive protein, white cell count, and ferritin. However, diagnosis can be challenging, and there is often a significant diagnostic delay, with patients often receiving multiple incorrect diagnoses before reaching a correct diagnosis.
Risk of AA amyloidosis in auto-inflammatory diseases
One of the most significant complications of auto-inflammatory diseases is AA amyloidosis. AA amyloidosis is caused by chronic inflammation and involves the systemic deposition of amyloid fibrils derived from the hepatic acute phase protein, serum amyloid A protein. Historically, AA amyloidosis was a major problem, particularly in familial Mediterranean fever, where a significant portion of affected individuals developed this complication. However, with advancements in treatment, the risk of AA amyloidosis has greatly reduced, and it can be entirely prevented by effectively treating the underlying chronic inflammatory disease.
Future directions in auto-inflammatory disease research
The future of auto-inflammatory disease research holds promise in multiple areas. One area of interest lies in the study of acquired auto-inflammatory diseases in adults, particularly the exploration of somatic mosaicism and its impact on pathology. Understanding the role of somatic mosaicism and the changes it brings as individuals age can shed light on disease mechanisms. Another area of interest is the potential for targeting the interferon pathway in treatment, as well as the NF-kappaB pathway. Additionally, exploring the inactivating inflammasomes and their role in regulating innate immunity will provide valuable insights. Overall, ongoing research holds the potential for improved diagnostics, targeted treatments, and a deeper understanding of auto-inflammatory diseases.
On this episode Lara and Vyanka talk to Prof Helen Lachmann all about autoinflammatory syndromes. This is ImmunoTea: Your Immunology Podcast, presented by Dr Lara Dungan and Dr Vyanka Redenbaugh. This is the show where we tell you all about the most exciting research going on in the world of immunology. So grab a cup of tea, sit down and relax and we'll fill you in. Contact us at ImmunoTeaPodcast@gmail.com or @ImmunoTea on twitter.