IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

Recently, we described 9 different ribonucleoprotein (RNP) subsets within
eukaryotic cells that often become targets for immune responses in patients
with systemic lupus erythematosus (SLE) and other connective tissue
diseases. Patient antibodies to these RNPs occurred selectively, and each
antibody was exquisitely specific in its ability to immunoprecipitate
individual RNP subsets. We hypothesize that these antibodies arise through
a specific process of "autoimmunization". We now plan to extend our observations to include antibodies directed at
components of deoxyribonucleoprotein (DNP). In combination with our
earlier studies, this work will provide a comprehensive picture of the
total spectrum of antibodies to nucleoproteins (both RNPs and DNPs) for
comparison with clinical and other laboratory data. These studies will utilize newly developed assays based on immunoblotting
(for analysis of protein antigens) and DNA-RNA hybridization (For detection
of RNA components). We will identify all of the nucleoprotein determinants
that participate frequently in the autoimmunity of SLE and compare the
autoimmune responses of SLE with those of drug-induced SLE and Epstein-Barr
virus infection. Once the precise targets are identified, we will
characterize them structurally and biochemically and determine if they
participate in the formation of circulating immune complexes. At a basic
level, our studies will provide new information about chromatin structure.
At a clincal level, they will determine whether nucleoprotein antigens are
likely to initiate and propagate autoimmune responses in SLE.
Identification of the mechanism(s) responsible for the induction of
antinuclear antibodies (ANAs) is likely to provide an understanding of the
etiology of SLE.