Cellular Analysis of Autoantibody-Producing Plasma Cells From Patients With Immune Cytopenias

Researchers

Project description

The secretion of antibodies by plasma cells is critical to fight infection and to establish long-term protective immunity. However, in autoimmune cytopenias, plasma cells produce antibodies that target select blood cell types, causing the body to mistakenly attack and destroy the blood cells. The "bad" plasma cells are difficult to study; they are thought to live in the bone marrow, which makes them hard to access, and they do not live well in laboratory culture conditions.

Dr. Go recently established an autoimmune cytopenia repository for the procurement of biological and clinical data for studies of immune-mediated disorders. In addition, Dr. Medina and Dr. Stegall have developed an in vitro plasma cell-stromal cell co-culture model that allows researchers to maintain human plasma cells in culture for an extended period of time.

The specific aim of this project is to use Dr. Medina and Dr. Stegall's co-culture model to analyze samples obtained from Dr. Go's autoimmune cytopenia repository. The collaboration will improve understanding of the biology of autoantibody-producing plasma cells in patients with autoimmune cytopenias.

Impact on patient care

Autoimmune cytopenias are relatively rare, affecting fewer than 200,000 people in the U.S., and treatments are limited. Patients who are resistant to first line therapy are at risk of life-threatening bleeding (immune thrombocytopenic purpura), anemia (autoimmune hemolytic anemia) or systemic infections (autoimmune neutropenia). For some autoimmune cytopenias, treatment of relapse or refractory cases is particularly challenging.

In addition, patients with chronic lymphocytic leukemia frequently have complications involving immune thrombocytopenic purpura or autoimmune hemolytic anemia. To address this aspect, Drs. Medina and Go met with Neil E. Kay, M.D., a clinician-researcher focused on this disease. According to Dr. Kay, autoimmune processes in patients with chronic lymphocytic leukemia are legendarily difficult, and autoimmune cytopenias are a major issue.

Through its research in the Center for Immunology and Immune Therapies, the team aims to develop treatments to eradicate autoantibody-producing plasma cells, or alternatively, to identify and characterize the antibodies that mediate the disease. The project has the unique potential to improve care and outcomes not only for patients with autoimmune diseases but also for patients with leukemia.

Funding

These discoveries and advances were made through the generous support of the Landow Family Fund.