NEUROPSYCHIATRIC DISEASE IN SJOGRENS-SYNDROME - ANTI-RIBOSOMAL-P AND ANTINEURONAL ANTIBODIES

PURPOSE: Patients with Sjogren's syndrome (SS) may develop nonfocal (i .e., psychiatric and/or cognitive dysfunction) as well as focal, neuro psychiatric disease (CNS-SS). Anti-ribosomal P and anti-neuronal antib odies have been associated with nonfocal neuropsychiatric disease in s ystemic lupus erythematosus (SLE), particularly psychosis and depressi on. This study examines the spectrum of psychiatric and cognitive dysf unction observed in SS patients with focal, as well as nonfocal, centr al nervous system (CNS) disease and relates these observations to the presence of serum and cerebrospinal fluid (CSF) anti-ribosomal and ant i-neuronal antibodies. PATIENTS AND METHODs. One hundred thirty-one pa tients-patients with primary SS (n = 91), patients with secondary SS ( n = 34), and mothers of infants with neonatal lupus erythematosus (NLE ) (n = 6)-were studied. Patients were referred to a large tertiary ref erral center and the population was highly selected for CNS Patients w ere evaluated clinically for focal and nonfocal CNS disease. Sera from 131 patients and 34 paired sera/CSF samples were examined by enzyme-l inked immunosorbent assay and radioimmunoassay for the presence of ant i-ribosomal P and anti-neuronal autoantibodies, respectively. Clinical features were categorized and autoantibody profiles obtained and corr elated independently for statistical significance. Data were analyzed using the two-tailed Fisher exact test. RESULTS: Psychiatric or cognit ive impairment, usually mild or moderate, occurred in over 80% (63 of 77) of this highly selected population of SS patients, and more than 6 0% of patients (48 of 77) had both. Anti-ribosomal P antibodies occurr ed in six (4.6%) patients with SS and related disorders. None of the p atients with primary SS had anti-ribosomal P antibodies, whereas they were present in a small number of patients with secondary SS (i.e., 4 of 34 [12%]) and in 2 of 6 mothers of infants with NLE. There was no c orrelation between nonfocal CNS disease, including psychosis or severe depression, and the presence of anti-ribosomal P antibodies. Paired s erum CSF samples from 34 SS patients with active CNS disease, includin g 6 with psychosis and 5 with severe depression, did not contain eithe r anti-ribosomal P or anti-neuronal antibodies. Anti-ribosomal P and a nti-neuronal antibodies were present in a control subset of SLE patien ts defined serologically by the presence of anti-nDNA antibodies. CONC LUSION: Patients with primary SS associated with CNS disease, includin g psychosis and depression, do not have serum or CSF autoantibodies to ribosomal P peptide or neuronal antigens, detected by binding to neur oblastoma cells. Thus, autoantibodies associated with nonfocal or diff use CNS disease in classical SLE (particularly psychosis and depressio n) are not present in CNS-SS. The observations suggest that nonfocal C NS disease in CNS-SS and CNS-SLE may be mediated by different immunopa thologic mechanisms. Potentially, these observations may have diagnost ic and therapeutic implications in the management of patients with CNS -SS and patients with CNS-SLE.