Background/Purpose: Neuropsychiatric (NP) manifestations in Systemic Lupus Erythematosus (SLE) are often associated with significant impact on quality of life and work capability. The underlying mechanisms behind NPSLE are still largely unknown. Here, we aimed to investigate the associations between the occurrence of Ro52 SSA autoantibodies and manifestations of NPSLE.

Methods: Presence or absence of SSA antibodies were detected with a non-quantitative in-house Ro52 ELISA in serum and cerebrospinal fluid (CSF) samples from a cohort of unselected SLE patients displaying neuropsychiatric features, collected between 2005 and 2011. Sensitivity of the assay was tested against confirmed Ro52 negative and positive individuals in serum. All SSA serum negative patients were also SSA negative in CSF indicating specificity of the assay. Blood brain barrier (BBB) permeability was calculated with the serum/CSF albumin ratio, and a ratio < 5.7 – 9 (age related) was considered to associate with an intact BBB.

Results: 55 NPSLE patients (mean age 50, 93% women) with paired serum and CSF samples were included in the analysis. Out of these, 40% (n=22) tested positive for SSA in serum. 64% (n=14) of SSA serum positive patients were also SSA positive in CSF (double positive), leaving 8 patients SSA positive in serum only (single positive). The distribution of major clinical NP manifestations in the total group of NPSLE patients was as follows (overlapping data): seizures 27% (n=15), headache 46% (n=25), cognitive dysfunction 31% (n=17), mood disorder or depression 11% (n=6) and stroke 11% (n=6). In the SSA double positive group this distribution was 29% (seizures), 29% (headache), 57% (cognitive dysfunction), 29% (mood disorder or depression) and 7% (stroke) respectively. There was a tendency that double positive patients had higher frequency of cognitive dysfunction than the other groups (57% (double positive) vs. 25% (single positive) and 31% (total)), however, this did not reach statistical significance. No clear differences were found between the groups concerning the other NP manifestations, distribution of ACR SLE criteria, age, disease duration, presence of brain lesions, cortisone treatment or smoking.

Conclusion: Presence of serum SSA autoantibodies in 40% of the NPSLE patients is in line with previous reports; however, our finding of high prevalence of double serum- and CSF SSA positivity in NPSLE patients was unexpected and indicates either facilitated passage over the BBB or intrathecal production of these autoantibodies. Our assay did not allow quantitative comparisons, but patients with confirmed intact BBB showed similar relation in SSA serum vs. CSF positivity, thus excluding BBB breakage as a main factor for detection of intrathecal SSA in this context. Moreover, intrathecal SSA tended to associate with cognitive dysfunction. Altogether, our results indicate the possibility of SSA antibodies interacting with cerebral functions, which may be in line with previous reports showing that other lupus-associated autoantibodies, i.e. anti-dsDNA antibodies, may cross react with neuronal N-metyl-D-aspartat (NMDA) receptors affecting neuron function and viability.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-proportion-of-intrathecal-ro52-ssa-antibodies-in-neuropsychiatric-lupus-patients-relations-to-neuropsychiatric-manifestations/