Patterns of autoimmunity to nucleoproteins in patients with systemic lupus erythematosus.

The ANAs described above can be accounted for on the basis of an immune response to just three nucleoprotein structures--the nucleosome, the U1 snRNP, and the Ro particle. When these nucleoproteins are looked at in turn, the following picture emerges. The nucleosome is identified by both anti-histone and anti-DNA antibodies. Anti-histone H1 and anti-histone H2B antibodies predominate and tend to occur together. They, as well as the anti-DNA antibodies with which they appear to be linked, recognize external features of the intact nucleosome. The U1 snRNP is recognized by both anti-U1 RNP and anti-Sm antibodies. Most so-called anti-U1 RNP antisera actually contain several linked sets of different antibodies that are directed against various polypeptides (68K, A, and C) found on the U1 snRNP. Anti-Sm antibodies are linked to the occurrence of anti-U1 RNP antibodies. The Ro particle is recognized by both anti-La and anti-Ro antibodies, and almost all sera that contain anti-La antibodies also contain anti-Ro antibodies. Thus, it appears that these three nucleoprotein particles become direct focal points for autoimmune responses in SLE. It is difficult to explain such focused responses on the basis of a general defect in immune regulation or spontaneous B-lymphocyte hyperactivity. Rather it appears that these nucleoproteins themselves are directly involved in determining which B-lymphocyte clones become activated. Thus, the simplest rationalization for the patterns with which these autoantibodies occur is to invoke the possibility that the particles themselves are directly triggering autoimmune responses.