Abstract

The autoimmune hemolytic anemia (AIHA). Much of what we currently know about the biology of this disease is form work on cold-reacting RBC autoantibodies. This form of AIHA has been more amendable to study because the antigens to which cold-reacting autoantibodies bind are well characterized and the ability to establish autoantibody-producing B-cells clones by EBV-transformation facilitates the study of autoantibody structure on a molecular level. In contrast, the more common and clinically-significant syndrome of autoimmune hemolysis id due to warm-reacting RBC autoantibodies and remains poorly understood with respect to the biochemistry of the autoantigen(s) and nature of the corresponding pathologic immune response. The major obstacle in studying this disease has been the inability to obtain sufficient quantities of autoantibodies which are homogeneous in structure and function. The proposed research will utilize a recently-described bacteriophage zeta cloning system to express in E. coli the repertoire of warm-reacting anti-RBC autoantibodies from a patient with warm AIHA. The antibody molecules thus produced will be used to identify the antigenic determinants to which warm-reacting red cell autoantibodies bind and explore the heterogeneity (clonality) of immunoglobulin variable gene usage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002621-03
Application #
3083045
Study Section
Research Manpower Review Committee (MR)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104