In the same August 1, 2000, issue of PNAS, is a closely related report titled: "Cloning and expression of a novel human antibody-antigen pair associated with Felty's syndrome." Its first author is immunologist Henrik Ditzel, assistant professor at The Scripps Research Institute, in La Jolla, Calif.

"In a lot of autoimmune diseases, like rheumatoid arthritis (RA), for example," Ditzel told BioWorld Today, "the general belief has been that T cells are the most important immune factor. There is increasing evidence that antibodies, too, are of importance. Neutrophils," he explained, "are a type of white cell very important for fighting bacterial infections. In RA you have this extra complication where patients, besides the basic arthritic symptoms, also have neutrophil destruction, caused by a separate autoimmune attack. And the combination is called Felty syndrome

"So autoantibodies directed against RA," Ditzel pointed out, "also have autoantibodies against neutrophils. But why this subgroup of patients exists is not known.

"Instead of looking at what antibodies in a patient's blood react to neutrophils, we isolated a reactive antibody and used it as bait for fishing out its target autoantigen. We found that two-thirds of Felty's syndrome patients, but none of the healthy donors, had high levels of the reactive antibody in their bloodstream.

"Instead of conventional methods for generating monoclonal antibodies," he went on, "we used phage display. We got a bone marrow sample from a patient, isolated the RNA, amplified the heavy and light chains of the immunoglobulin, and expressed these antibodies on the surface of phages, which at the same time have the genetic code for that antibody molecule.

"Then we selected that library on tissue where we believed autoantigens were targeted by these autoantibodies." Ditzel observed , "The method we have developed to identify this autoantigen in Felty's syndrome can be applied to a lot of different autoimmune diseases, such as diabetes and RA itself." - David N. Leff

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