Probing the human natural autoantibody repertoire using an immunoscreeningapproach

While an increasing number of studies report the presence of antibodies cap able of recognizing self-antigens, the function of these natural autoantibo dies remains elusive. A variety of concepts has been advanced ranging from evolutionarily tolerated but non-functional natural autoantibodies to autoa ntibodies effectuating various biological functions. Known IgM, IgG, and Ig A natural autoantibodies are directed against various antigens, including n uclear and cell surface proteins. To explore further autoantibodies and the ir autoantigens, we employed an immunological screening method called SEREX recently used to characterize tumour-expressed antigens eliciting an immun e response in patients [1]. Sera from 12 individuals were used to screen a cDNA expression library prepared from a cytogenetically normal meningioma t o identify antigens reactive with normal human sera from individuals withou t obvious disease. Nineteen reactive normal antigen clones were identified representing 15 different antigens, including nine genes with known functio ns, five genes with unknown functions, and one gene with a novel sequence n ot present in the databases. Of the 12 individual normal sera tested, 75% w ere reactive to one or more of the 15 different antigens with two highly re active sera demonstrating reactivity with 33% of the antigens. When screeni ng the same meningioma expression library with serum from the patient, eigh t antigens were identified that were totally different from those identifie d using sera from normal individuals. This SEREX immunological screening me thod presents a new option for probing the natural autoantibody repertoire and identifying normal antigens whose functions may provide additional insi ghts into how natural autoantibodies effectuate various biological function s.