title: Neuropsychiatric disease in Sjögren's syndrome: anti-ribosomal P and anti-neuronal antibodies.
abstract: OBJECTIVE
  Patients with Sjögren's syndrome (SS) may develop nonfocal (i.e., psychiatric and/or cognitive dysfunction) as well as focal, neuropsychiatric disease (CNS-SS). Anti-ribosomal P and anti-neuronal antibodies have been associated with nonfocal neuropsychiatric disease in systemic lupus erythematosus (SLE), particularly psychosis and depression. This study examines the spectrum of psychiatric and cognitive dysfunction observed in SS patients with focal, as well as nonfocal, central nervous system (CNS) disease and relates these observations to the presence of serum and cerebrospinal fluid (CSF) anti-ribosomal and anti-neuronal antibodies.
  
  
  METHODS
  One hundred thirty-one patients--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 referral center and the population was highly selected for CNS disease. Patients were evaluated clinically for focal and nonfocal CNS disease. Sera from 131 patients and 34 paired sera/CSF samples were examined by enzyme-linked immunosorbent assay and radioimmunoassay for the presence of anti-ribosomal P and anti-neuronal autoantibodies, respectively. Clinical features were categorized and autoantibody profiles obtained and correlated independently for statistical significance. Data were analyzed using the two-tailed Fisher exact test.
  
  
  RESULTS
  Psychiatric or cognitive impairment, usually mild or moderate, occurred in over 80% (63 of 77) of this highly selected population of SS patients, and more than 60% of patients (48 of 77) had both. Anti-ribosomal P antibodies occurred in six (4.6%) patients with SS and related disorders. None of the patients 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 correlation between nonfocal CNS disease, including psychosis or severe depression, and the presence of anti-ribosomal P antibodies. Paired serum CSF samples from 34 SS patients with active CNS disease, including 6 with psychosis and 5 with severe depression, did not contain either anti-ribosomal P or anti-neuronal antibodies. Anti-ribosomal P and anti-neuronal antibodies were present in a control subset of SLE patients defined serologically by the presence of anti-nDNA antibodies.
  
  
  CONCLUSIONS
  Patients with primary SS associated with CNS disease, including psychosis and depression, do not have serum or CSF autoantibodies to ribosomal P peptide or neuronal antigens, detected by binding to neuroblastoma cells. Thus, autoantibodies associated with nonfocal or diffuse CNS disease in classical SLE (particularly psychosis and depression) are not present in CNS-SS. The observations suggest that nonfocal CNS disease in CNS-SS and CNS-SLE may be mediated by different immunopathologic mechanisms. Potentially, these observations may have diagnostic and therapeutic implications in the management of patients with CNS-SS and patients with CNS-SLE.
authors.affiliation: Specialty Laboratories, Inc., Santa Monica, California.
authors.forename: R
authors.initials: R
authors.lastname: Spezialetti
authors.forename: H G
authors.initials: HG
authors.lastname: Bluestein
authors.forename: J B
authors.initials: JB
authors.lastname: Peter
authors.forename: E L
authors.initials: EL
authors.lastname: Alexander
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000032:analysis*; D002493:Central Nervous System Diseases / Q000150:complications / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000276:immunology*; D015800:Protozoan Proteins; D011618:Psychotic Disorders / Q000150:complications / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000150:complications / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; C064601:L12E protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D012269:Ribosomal Proteins