Abstract
Several questions about SLE pathogenesis have continued to puzzle investigators over decades.
A major question in the pathogenesis of SLE is the role of self-antigen. Early studies suggested that SLE was characterized by B cell hyperresponsiveness to all antigens. This suggested no role for autoantigen-specific T helper cells. The broad spectrum of autoantibodies in SLE has also been related to polyclonal B cell activation. Moreover, the presence of high levels of interferon could result in a polyclonal defect in B cell tolerance and activation. On the other hand, the association between HLA and particular autoantibody responses suggests the presence of autoantigen- specific T cells. Any one individual with SLE may have a narrow spectrum of autoantibodies., and not all conditions with high interferon lead to the same spectrum of autoantibodies that is seen in SLE.
Another question has been the cell lineage responsible for the aberrant immune response. Genetic analyses suggest aberrant function of B cells and dendritic cells, not T cells nevertheless, substantial evidence for critical T cell defects exist.
Finally, the role of microbial infection, especially EBV, in SLE has never been resolved.
