A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating presentations of SLE and comprises of psychiatric, central and peripheral neurological signs and symptoms. Previous studies suggest the possible associations between various autoantibodies (Abs) and NPSLE. The magnitudes of such association varied between studies. We performed a meta-analysis to pool data on serum and cerebrospinal fluid (CSF) levels and positivity of Abs in blood and cerebrospinal fluid in patients with NPSLE and SLE. A systematic literature search was conducted to identify studies that fulfilled inclusion criteria. A random-effects model was used to calculate overall combined odd ratio (OR) and mean levels with its corresponding 95% confidence interval to evaluate the relationship between individual Abs and NPSLE patients relative to SLE patients. Forty-one studies met the inclusion criteria and were used in this analysis. There was a significantly greater proportion of NPSLE patients who demonstrated positivity for serum anti-cardiolipin (aCL) Abs (OR=1.63, p=0.016), lupus anticoagulants (LA) Abs (OR=1.91 p=0.01), anti-phospholipid (APL) Abs (OR=2.08, p=0.001), anti-ribosomal P Abs (OR=2.29, p<0.001), anti-neuronal Abs (OR=9.50, p<0.001) as compared to SLE patients. In NPSLE patients, there was a significant increased prevalence of positive titres for CSF anti-neuronal Abs (OR=36.84, p=0.001) as compared to SLE patients. Among the 19 neuropsychiatric syndromes, the positivity of these serum autoantibodies were found specifically significantly associated with the manifestations of mood disorder, psychosis, cerebrovascular disease, seizure disorders, acute confusional state, cognitive dysfunction, headache, movement disorder, demyelinating syndrome and polyneuropathy, with ORs ranging from 1.84 to 4.73. Meta-regression identified proportion of women as significant moderator for the heterogeneity of aCL (p=0.004) and anti-neuronal Abs (p=0.0007); mean age for the heterogeneity of aCL (p=0.042) and LA (p=0.020) Abs, mean duration of illness for the heterogeneity of aCL Abs (p=0.035), and mean SLEDAI scores for the heterogeneity of anti-ribosomal P Abs (p=0.014). NPSLE patients are more likely to have elevated serum levels of aCL, LA, APL, anti-ribosomal P Abs and anti-neuronal Abs compared with SLE patients. Further research is required to evaluate the accuracy of using the above antibodies as an adjunct diagnostic tool in NPSLE.

Keywords: Adjunct diagnostic tool; Autoantibody; Neuropsychiatric systemic lupus erythematosus (NPSLE).