Eric Meffre PhD

My career has been centered on basic human immunology and translational research. My expertise allows me to determine how B-cell tolerance is established in healthy donors and patients with primary immunodeficiencies or autoimmune diseases by assessing the frequency of autoreactive B cells using a RT-PCR based strategy. This method consists in amplifying and cloningimmunoglogulin genes from single B cells. One of my main research goals is to continue the investigation and characterization of the role played by B cells in the development of autoimmunity, a paradoxical complication of many patients affected by primary immunodeficiencies. As a consequence, I was recruited to Yale University in 2009 as part of a new initiative in Human and Translational Immunobiology.
My work is focusing on the etiology of autoimmune diseases affecting millions of individuals in the world. We continue the identification and characterization of molecules and pathways involved in the establishment of B-cell tolerance through the investigation of rare patients with primary immunodeficiency (PID), enrolled through an international network. The replication of our observations in several autoimmune diseases favored by risk alleles reproducing abnormal tolerance features characterized in PID patients, demonstrates our efforts to identify the cellular mechanisms underlying these diseases. Our latest investigations revealed that central B-cell tolerance defects and the failure to remove developing autoreactive B cells are primary to many autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, and result from genetic polymorphisms such as the R620W PTPN22 risk allele. Understanding the etiology of autoimmunity is the first step toward effective treatment and an ultimate aim would be the development of therapies targeting the causes of these disorders.