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New Findings on Immune Dysfunction and Lymphoma Risk (Binder Lab)
Lymphocytes are essential for health, but when they malfunction, they can cause immune deficiencies, autoimmune diseases, or cancer. Autoimmune disorders and certain blood cancers, such as non-Hodgkin’s lymphoma, share similar disease processes that often originating from self-reactive lymphocytes. However, beyond laboratory models, the role of distinct recurring genetic mutations in this multistep transformation remains unclear, as most human data come from diagnosed cases. Understanding how single-gene changes drive early immune dysfunction or lymphoma development could improve detection, treatment, and prevention.
Researchers in the Binder Lab, with Christoph Schultheiss and Paul Schmidt-Barbo as the lead authors, have uncovered new insights into how genetic mutations contribute to immune system disorders and the risk of developing lymphoma. Their latest study, published in the Journal of Allergy and Clinical Immunology focuses on deficiency of adenosine deaminase 2 (DADA2)—a rare genetic autoinflammatory disease caused by mutations in the ADA2 gene, which is also frequently altered in diffuse large B-cell lymphoma. Analyzing 52 DADA2 patients, they found low antibody levels, a loss of memory B and T cells, and persistent especially TNF-mediated inflammation, even in individuals receiving treatment. A key discovery was a skewed B-cell profile with increased IGHV4-34 gene rearrangements, a pattern associated with both autoimmunity and lymphoma. To further investigate the DADA2-specific immunogenetic architecture, the team developed a machine learning tool that accurately distinguishes DADA2 patients from healthy individuals based on features of their adaptive immune receptor architecture alone.
These findings highlight the unique immunotype of DADA2 patients with features of autoimmunity and lymphoma, shed new light on the links between immune dysfunction and lymphoma development and offer promising directions for early detection, treatment, and prevention.
The DBM would like to congratulate the Binder Lab on this accomplishment.