As part of this year’s Education Program, experts will lead a case-based discussion of the diagnosis, clinical spectrum, and treatment options for patients with primary immunodeficiency diseases (PIDDs). Experts will provide guidance for adult and pediatric hematologists to identify PIDDs, which predispose patients to infection, immune dysregulation/autoimmunity, and malignancy. Here, session chair Roshini Sarah Abraham, PhD, from Nationwide Children’s Hospital in Columbus, Ohio, tells us what viewers can expect to learn from this session, which features the perspectives of a diagnostic immunologist and clinical hematologists.
What is meant by the “yin and yang” relationship between autoimmunity and immunodeficiencies?
Patients with genetic disorders of the immune system are classified as having inborn errors of immunity. In the early days of the field, it was thought that a genetic disorder of the immune system, which resulted in the loss of function of a particular immune-related gene, primarily resulted in a predisposition to infections. More recently, researchers have found that inborn errors of immunity also include diseases that predispose individuals to immune dysregulation, resulting in autoimmunity and susceptibility to malignancies. The yin and yang, in the context of inborn errors of immunity, refer to these seemingly opposing entities of infection susceptibility and immune dysregulation.
How has the diagnosis and treatment of autoimmune disorders and immunodeficiencies changed?
Over the past few decades, there has been a surge in complex diagnostic tools in immunology. These tools have improved our ability to diagnose these disorders earlier and intervene appropriately. Providing a molecular diagnosis and confirming an inborn error of immunity as the cause of autoimmune cytopenias or other hematologic manifestations facilitates better communication with our hematology colleagues who routinely care for these patients. The ability to offer a molecular diagnosis also allows for more tailored, precise therapies.
The curative treatment for several inborn errors of immunity used to be hematopoietic cell transplantation, but we now have gene therapy options for some of these defects, and we also are able to repurpose targeted therapies in some cases to deliver personalized medicine.
What will you and the other speakers be discussing in your presentations?
I will focus on the diagnostic immunology laboratory evaluation for PIDDs that are associated with autoimmune cytopenias, including basic and advanced testing for evaluation of specific immune pathways, using a case-based approach.
Markus Seidel, MD, from the Medical University of Graz in Austria, will discuss how a molecular diagnosis can facilitate the development of personalized treatment plans and medical management for patients with autoimmune cytopenias and immune dysregulation, as well as the role of immunophenotypic biomarkers in therapeutic decision-making.
Emma Morris, MB BChir, PhD, MRCP, FRCPath, from University College Hospital in London, will review the role of hematopoietic cell transplantation in the treatment of patients with PIDDs who present with autoimmune cytopenias, and discuss the problems that make transplantation in this setting particularly challenging. She also will talk about the role of gene therapy and gene-editing approaches for the treatment of inborn errors of immunity.
What do you hope attendees learn about autoimmune disorders and immunodeficiency from this session?
Our goal is to increase practicing hematologists’ awareness of this group of patients. Hematologists may not recognize that some patients presenting with autoimmune cytopenias may have an underlying PIDD, which can change the diagnostic approach and management. Through case studies, we want to walk through performing the diagnostic workup using clinically available diagnostic tools and discuss access to research tools for more complex patients. Then, again through case studies, we will cover how to couple the molecular diagnosis of inborn errors of immunity with potential targeted or curative therapies.