Hospital for Special Surgery

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$482,000.00 (Est.) for: Fiscal Year 2005
Start date for award is 8/15/05
Percent of funding associated with the use of human subjects: 21-40

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Hospital for Special Surgery
Most recent approval: 05/20/05
IRB approval number: 23076

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects: Fiscal Year 2005

Type(s) of Human Subjects Involvement:

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

We aim to determine the mechanisms that regulate B cell tolerance in healthy humans but are defective in rheumatoid arthritis (RA) patients. The working hypothesis is that RA B cells suffer from intrinsic B cell receptor (BCR) signaling defects that impinge on the proper counterselection of developing autoreactive B cells and result in the abnormal recruitment and activation of peripheral self-reactive B cells into the synovium. The first aim of the project will consist of characterizing the molecular basis for early defects in B cell tolerance checkpoints in RA by comparing microarray gene expression profiles from control and RA B cell subpopulations (whether or not triggered by their BCR) that may reveal specific BCR signaling defects for the different subgroups of RA patients. The second part of the project will identify alternative B cell tolerance mechanisms such as anergy that can substitute for defective receptor editing in humans. The third part of the project will analyze how B cell tolerance is broken in the synovium of RA patients. These studies have significant implications for understanding how people with autoimmune diseases produce antibodies that attack their body and may provide clues for development of new medications.