AUTOANTIBODIES AGAINST NUCLEAR DOTS IN PRIMARY BILIARY-CIRRHOSIS

Autoantibodies against nuclear proteins are not always but rather freq uently present in sera of patients with primary biliary cirrhosis (PBC ). The specificity and diagnostic value of these autoantibodies for PB C have only recently become clear through cloning of the cDNA of some of the corresponding autoantigens which allowed the establishment of i mmunological assays with recombinant autoantigens expressed in E. coli and eukaryotic cells. In this report we summarize primarily the knowl edge on the structure and putative function of two nuclear autoantigen s, the Sp100 and PML proteins, which are present in so-called nuclear dots (NDs) and against which autoantibodies are present in a subpopula tion of PBC patients. Furthermore, the type of autoimmune response (ep itope specificity and immunoglobulin class) against both the Sp100 and PML proteins and the specificity of the anti-Sp100 and anti-PML autoa ntibodies for PBC patients and patients with other autoimmune diseases is reviewed. Current knowledge clearly indicates that determination o f anti-Sp100 and anti-PML autoantibodies substantially improves diagno sis of PBC as these autoantibodies are highly specific for this diseas e even when autoantibodies against mitochondrial antigens, a hallmark of most PBC patients, are not found. The type of autoimmune response a gainst the Sp100 and PML proteins also provides some dikes about possi ble mechanisms which lead to autoantigenicity of both proteins.