Ep. 65: “Primary Immunodeficiency Disorders” Featuring Dr. Siobhan Burns
Oct 24, 2023
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Dr. Siobhan Burns, a Professor of Translational Immunology, discusses primary immunodeficiency disorders and genetic mutations affecting immune function. Topics include inborn errors of immunity, a cryptic antigen in influenza, drug-resistant malaria parasites, transplanting genetically modified pig kidneys, reducing immunosuppression after liver transplant, and mechanisms of inborn errors of immunity.
Differentiating between pediatric and adult patients can affect the types of immune deficiencies encountered.
Research efforts focus on understanding how specific genetic mutations impact cell function in inborn errors of immunity.
Understanding the mechanisms underlying STAT gain-of-function mutations is crucial for developing targeted therapies.
Deep dives
Understanding Inborn Errors of Immunity
Inborn errors of immunity encompass a wide range of disorders that impact different parts of the immune system. These include deficiencies in T cells, B cells, or neutrophils, as well as specific signaling pathways. Patients with inborn errors of immunity often present with recurrent or unusual infections, along with autoimmune and allergic complications. Differentiating between pediatric and adult patients can affect the types of immune deficiencies encountered.
Research Focus: Genetic Mutations and Cell Function
Research efforts are focused on understanding how specific genetic mutations impact cell function in inborn errors of immunity. This involves analyzing genetic sequences, identifying mistakes in novel genes, and determining their effect on protein function. The goal is to develop a better understanding of the pathogenesis of these disorders and identify potential targets for therapy. Additionally, studying the variations in clinical phenotypes among patients with different mutations in the same gene is important for providing accurate prognoses and optimizing treatment approaches.
Insights from Studying STAT Gain-of-Function
The study of STAT gain-of-function mutations, such as in STAT1, has provided insights into the impact of constitutive activation of pro-inflammatory pathways on the immune system. Overactive STAT proteins can disrupt normal signaling pathways, impact dimer formation, and alter DNA binding, leading to immune dysfunction. Understanding the mechanisms underlying these mutations and their effects on immune cells is crucial for developing targeted therapies.
Challenges in Diagnosis and Treatment
While genetic diagnoses for inborn errors of immunity have improved, there is still a gap between diagnosis and effective management. Limited drug therapies are available for specific pathways affected by genetic mutations, and hematopoietic stem cell transplantation is commonly used in children but less frequently in adults. Challenges remain in treating age-related complications, organ damage, and uncontrolled inflammation in adult patients.
The Limitations of Science
The biggest misconception about science is that it has the ability to answer all questions and solve all problems. While science has made significant progress, there are limits to its reach. Some aspects of life, love, faith, and the universe may not be fully explained by scientific inquiry.
Dr. Siobhan Burns is a Professor of Translational Immunology at University College London. Her group studies the underlying molecular and cellular mechanisms that give rise to primary immunodeficiency disorders. She talks about how genetic mutations affect immune function, and what inborn errors of immunity can teach us about general immunology.
