Background A number of sera from patients with connective tissue diseases that immunoprecipitated high molecular weight (hmw) nucleic acid smear have been found in RNA-immunoprecipitation (IPP) assay. Most of these sera are supposed to contain autoantibodies for DNA- or mRNA- (or its precursor) related proteins. However, neither the characteristics of antigens nor the clinical significance have been well-defined.

Objectives To analyse the corresponding antigens for autoantibodies immunoprecipitating hmw-nucleic acid smear and to elucidate the clinical features associated with these autoantibodies.

Methods We examined 63 sera from patients with various kinds of connective tissue diseases that immunoprecipitated hmw nucleic acid smear by RNA-IPP. IPP using [35S] methionine-labelled HeLa cell extracts was performed for analysis of the protein components. Immunoprecipitated nucleic acid components were treated with DNase I or RNase A to identify either DNA or RNA.

Results DNA and a heterodimer of 70 kDa and 80 kDa proteins (p70/p80) that was identified as the Ku antigen, was immunoprecipitated by 16 patient sera (4:SLE, 7: myositis overlap syndrome, 1: interstitial pneumonia (IP), 4: undiagnosed). In addition, DNA-protein complex consisting of four polypeptides (11 kDa-21 kDa) that appeared to be histone core proteins, was immunoprecipitated by 18 sera (12:SLE including one drug-induced lupus, 5:MCTD/overlap syndrome, 1: autoimmune hepatitis). Eight patients sera (5:SLE, 2:RA, 1:IP) reacted with the 140 kDa protein along with hmw-RNA smear that was supposed to be RNA helicase A. It should be noted that the remaining 37 of 63 (59%) patients sera immunoprecipitated none of proteins with defined specificities, but various unidentified proteins.

Conclusion Autoantibodies to the Ku, histone, and RNA-helicase A have been identified in patients sera with SLE and other rheumatic diseases that immunoprecipitated hmw-nucleic acid smear. However, a high percentage of these sera were found to contain novel hmw nucleic acids-related antibodies. Further analysis of these autoantibodies may provide clues for understanding the pathogenic mechanism of connective tissue diseases.