Anti-P antibodies and neuropsychiatric lupus erythematosus

Abstract

A high proportion of patients with SLE develop neuropsychiatric lupus during the course of their disease. The expression of disease varies significantly in terms of clinical manifestations, onset, and severity, so that this form of lupus remains a major diagnostic and therapeutic challenge. Because affected tissue cannot be sampled and animal models are not readily available, scientific investigation is considerably hampered. Approximately 15% of lupus patients have anti-P antibodies. These autoantibodies are highly specific for SLE. Most series show a highly significant association between anti-P and lupus psychosis, and this result is now confirmed in a series of 336 SLE patients. The mechanism explaining this association is uncertain and may simply reflect an immune response to damaged tissue. However, the possibility that the antibodies are pathogenic by directly binding to cell-surface receptors on neuronal cells or that they penetrate cells and inhibit protein synthesis within the cell requires further investigation. Whether T cells are involved in the pathogenesis of CNS disease is an important question that has received little attention. As in the CNS of patients with multiple sclerosis and patients with other autoimmune diseases, excess production of cytokines may contribute significantly to organ inflammation. We report associations between anti-P autoantibodies and certain MHC class II alleles, particularly HLA-DQB1*0602. These findings support a role for T cells in anti-P autoantibody production and encourage further studies of the role of autoantigen-specific T and B cells in injury to the central nervous system.