Antibodies to cellular prion protein and its cognate ligand stress-inducible protein 1 in systemic lupus erythematosus.

OBJECTIVES This study aimed to determine the prevalence of autoantibodies to cellular prion protein (PrP(C)) and its cognate ligand stress-inducible protein 1 (STI-1) in sera from patients with systemic lupus erythematosus (SLE), and their possible correlation with clinical and serological SLE manifestations. METHODS Sera were obtained from 103 consecutive SLE patients and 77 healthy controls. IgG antibodies to PrP(C) and to STI-1 were determined by ELISA using recombinant purified proteins, and the reactivities were confirmed by immunoblotting. A panel of lupus-related autoantibodies was investigated by well-standardized techniques. Clinical data were obtained by extensive chart review, and disease activity was scored using the SLE Disease Activity Index (SLEDAI). RESULTS The frequency of anti-PrP(C) antibodies in SLE (7.8%) was similar to healthy controls (p = 0.56), but these antibodies were significantly associated with previous central nervous system (CNS) involvement when compared with patients without anti-PrP(C) (33.3% vs. 7.5%; p = 0.04). On the other hand, anti-STI-1 reactivity was more frequently observed in SLE patients than in healthy controls (12.6% vs. 2.6%; p = 0.026), and this reactivity was associated with a lower frequency of renal disease (23.1% vs. 54.4%; p = 0.04). These two antibody specificities were not associated with SLEDAI score or with the presence of lupus autoantibodies (p > 0.05). CONCLUSION This is the first evidence of reactivity to PrP(C) in SLE. The intriguing association of these antibodies and previous CNS involvement raises the possibility of a pathogenic role for them in SLE CNS damage.