2011 Human Lupus Biology
2012 B Cells
Clonal Expansion and Selection of B cells in SLE
The Study and What it Means for Patients
“We are using high-throughput DNA-sequencing technology to identify specific B cells that may cause lupus in individual patients. Different B-cell-targeted lupus therapies such as Benlysta® (belimumab), aim to control the disease by clearing different disease-causing B cells from the immune system. But currently physicians do not know which types of B cells should be eliminated. We hope that our study will take the guesswork out of matching B-cell treatments to patients, improving individualized therapy.”
In lupus, B cells that make antibodies targeted against components of the body’s own cells, such as DNA, are selectively expanded in numbers. The autoantibodies that these B cells make can damage organs and their detection in a patient’s blood is useful diagnostic for lupus. New B-cell targeted lupus therapies, such as the recently approved Benlysta® (belimumab), aim to control the disease by clearing out disease causing B cells from the patient’s immune system. Different therapies preferentially target different types of B cells but physicians currently have no way of telling which particular B cell type causes disease and therefore needs to be eliminated. We will use the latest high-throughput DNA sequencing technology to identify disease-causing B cells in patients with lupus based on genes coding for antibodies. If successful, physicians could then monitor their patients for the presence of harmful B cells, allowing them to select the best B cell therapies for a particular patient.
Clonally expanded B cells with anti-nuclear specificities are characteristic of systemic lupus erythematosus (SLE). Monitoring the B cell repertoire with greater resolution is an increasingly sought after goal, as more physicians are using B cell targeted therapies for their patients and the range of B cell targeting agents expands to target different B cell populations. The rational use of these agents requires an individualized approach to therapy that can be guided by repertoire studies to determine if therapy is changing the repertoire (or if resistant B cell clones remain) and at which stage(s) of B cell development tolerance may break down and are therefore the most appropriate to target. To begin to address these questions, we herein propose to analyze the B cell repertoire of patients with SLE and healthy control subjects for clonal expansion and selection using high throughput sequencing (HTS) of antibody heavy chain genes. We will use HTS to measure the frequency and diversity of expanded B cell clones in persons with SLE and healthy controls. We will compare antibody repertoire in different B cell subsets. These new methods for the detection of expanded B cell clones and antibody repertoire may improve individualized therapy for autoimmunity.