Pathogenic aspects of systemic lupus erythematosus (SLE)

Antibodies against native DNA are a disease-specific marker for systemic lupus erythematosus (SLE) and in addition, there is direct evidence that these antibodies also play a major part in pathogenic mechanisms leading to systemic and organ-specific disease manifestations. The origin of anti-dsDNA antibodies is still poorly understood, especially as dsDNA per se is not immunogenic. As recently shown, evidence is now accumulating that anti-dsDNA antibodies are most likely germline-encoded and antigen-selected, as demonstrated by sequence analysis of human anti-dsDNA antibody clones from SLE patients. With regard to the possible autoantigen it is of interest that sera of SLE patients show an elevated level of nucleic acids, which at least can partly be explained by defective clearance mechanisms. The question, however, whether these nucleic acids could serve as an autoantigen triggering off anti-dsDNA antibodies has not yet been solved.