Ribosomal P autoantibodies in systemic lupus erythematosus: Frequencies in different ethnic groups and clinical and immunogenetic associations

Objective. To determine the frequencies and clinical associations of antiribosomal P antibodies (anti-P) in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE), and to assess whether anti-P was associated with any major histocompatibility complex (MHC) class II alleles or shared amino acid sequences. Methods. Sera from 394 SLE patients were studied for anti-P using an enzyme-linked immunosorbent assay, and MHC class II alleles (HLA-DRB1, DQA1, and DQB1) were determined by DNA oligotyping. Results. Anti-P antibodies were found in 13-20% of patients in the majority of ethnic groups, but were perhaps more frequent in Chinese patients (36%) and less common in Bulgarian patients (6%). Neuropsychiatric lupus (psychosis and/or depression) was significantly associated with anti-P. The HLA-DR2, DQ6 haplotypes DRB1*1501 or *1503, DQA1*0102, and DQB1*0602 were increased in anti-P-positive whites, blacks, and Mexican Americans. The HLA-DQB1*0602 allele showed the strongest association with anti-P when these 3 ethnic groups were combined and compared with both race-matched anti-P-negative SLE patients and normal controls. The HLA-DQ8 specificity (DQB1*0302) was increased both in whites and inMexican-Americans with anti-P who were negative for HLA-DQB1*0602, and perhaps also increased in Greeks, but not in blacks, in whom HLA-DQB1*0301 was increased. A shared amino acid sequence in HLA-DQB1 (at position 26 of leucine and position 30 of tyrosine) was strongly associated with anti-P positivity (70%) versus anti-P negativity (42%) across ethnic lines. Conclusion. The anti-P response in SLE patients, occurring in ~15% of patients, was strongly influenced by certain MHC class II alleles and was correlated with diffuse neuropsychiatric dysfunction

Anti-Endothelial Antibodies and Neuropsychiatric Systemic Lupus Erythematosus

The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) has been attributed to autoantibody-mediated neural dysfunction, vasculopathy, and coagulopathy. Several autoantibodies specificities have been reported in serum and cerebrospinal fluid of NPSLE patients (i.e., antineuronal, antiribosomal P proteins, antiglial fibrillary acidic proteins, antiphospholipid, and anti-endothelial antibodies). We have recently demonstrated an association between serum anti-endothelial antibodies and psychosis or depression in patients with SLE. Subsequently, by screening a cDNA library from human umbilical artery endothelial cells with serum from a SLE patient with psychosis, one positive strongly reactive clone was identified encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family. Anti-Nedd5 antibodies have been found significantly associated with psychiatric manifestations in SLE patients, strengthening the view of a possible implication of autoantibodies in the development of psychiatric disorders. © 2006 New York Academy of Sciences