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 in Mexican‐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.