Km. Neugebauer et al., SR proteins are autoantigens in patients with systemic lupus erythematosus- Importance of phosphoepitopes, ARTH RHEUM, 43(8), 2000, pp. 1768-1778
Objective. To determine whether members of the highly phosphorylated SR pro
tein family are autoantigens and, if so, to determine the frequency and mol
ecular basis of antigen recognition.
Methods. Native human SR proteins were purified to homogeneity from HeLa ce
lls, and an enzyme-linked immunosorbent assay (ELISA) was developed. Furthe
r studies employed immunoblotting of both phosphorylated and dephosphorylat
ed SR proteins.
Results. Anti-SR protein reactivity was frequently detected in the sera of
patients with systemic lupus erythematosus (SLE), Sera from 52% of the SLE
patients in a group of patients with a variety of auto-immune and other dis
orders (n = 137) and from 50% of the SLE patients in a separate group (n =
102) were positive in an ELISA. In contrast, sera from patients with other
disorders, such as rheumatoid arthritis and primary antiphospholipid syndro
me, reacted infrequently. Reactivity with double-stranded DNA (dsDNA), used
in the diagnosis of SLE, did not correlate with SR protein reactivity. Ant
i-SR autoantisera did not bind highly charged unphosphorylated peptides rel
ated to the SR domain, which is rich in arginine and phospho-serine residue
s. Surprisingly, many of the epitopes were influenced by the presence or ab
sence of SR protein phosphorylation. In immunoblots, some patient sera lost
reactivity upon SR protein dephosphorylation, while others significantly g
ained reactivity.
Conclusion. We have identified a novel set of autoantigens in SLE, the SR p
rotein family of non-small nuclear RNP pre-messenger RNA splicing factors.
Anti-SR autoantibodies are distinct from those which bind dsDNA, The identi
fication of this new set of autoantigens and the observation that the auto-
epitope(s) involves posttranslational modification offer new possibilities
for understanding autoimmunity and its development.