Serum lymphocytotoxic antibodies in neuropsychiatric lupus: a serial study

The pathogenesis of neuropsychiatric (NP) SLE remains speculative. A relationship between circulating brain cross-reactive lymphocyte antibodies (LCA) and NP-SLE has been postulated but serial, prospective study of LCA in individual patients with SLE has rarely been performed. In the current study a group of 34 patients with SLE was analyzed using clinical, neurologic, psychiatric, and neuropsychological examinations, together with routine serological tests, to define NP-SLE. Previous history of alloimmunization was also recorded. LCA were measured by a two-stage microcytotoxicity assay against a panel of 25 normal donor B and T cells, at both 40 and 37 degrees C. LCA by this method were found in the serum of 20/34 (58%) SLE, 2/22 (9%) rheumatoid arthritis, and 3/24 (12%) antinuclear-antibody-positive chronic psychiatric patients (P less than 0.01). Analysis of LCA serially in individual SLE patients revealed: (1) No difference in B- or T-cell reactivity at either 4 or 37 degrees C, (2) no significant correlation between previous alloimmunization and the presence of LCA, (3) fluctuations in LCA associated with NP-SLE relapses or remissions, but not with therapy, in 10 patients prospectively studied. A significant positive association was found between the occurrence of single neuropsychiatric events and serial LCA determinations in 180 sera (P less than 0.000001). LCA as measured in this study appear more frequently in SLE than in controls and may indicate active NP-SLE in some patients. Further study of the pathogenic role and diagnostic value of LCA in NP-SLE, including their relationship to subtle neurocognitive changes, is proposed.