Brain metabolism and autoantibody titres predict functional impairment in systemic lupus erythematosus

Abstract

ObjectiveWe investigated whether systemic lupus erythematosus (SLE) disease duration or serology associate with abnormal regional glucose metabolism as measured with [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and deficits on neuropsychological testing.MethodsSubjects with SLE with stable disease activity, without brain damage or clinical symptoms of neuropsychiatric (NP) SLE, stratified by disease duration (short-term (ST)-SLE=disease ≤2 years, long-term (LT)-SLE=disease ≥10 years), underwent clinical assessments, neuropsychological testing, resting FDG-PET scan imaging and measurement of serum titres of antibody to N-methyl-d-aspartate receptor (DNRAb). FDG-PET scans were compared with age-matched and gender-matched healthy controls.ResultsSubjects with LT-SLE demonstrated hypometabolism in the prefrontal and premotor cortices that correlated with accrued SLE-related damage, but not with DNRAb titre or performance on NP testing. Independent of disease duration, subjects with SLE demonstrated hypermetabolism in the hippocampus and orbitofrontal cortex that correlated with impaired memory performance and mood alterations (depression, anxiety, fatigue). Serum DNRAb also correlated independently with impaired memory performance and increased anxiety. Together, serum DNRAb titre and regional hypermetabolism were more powerful predictors of performance than either alone.InterpretationThe presence of serum DNRAbs can account for some aspects of brain dysfunction in patients with SLE, and the addition of regional measurements of resting brain metabolism improves the assessment and precise attribution of central nervous system manifestations related to SLE.

Cognitive Dysfunction in Systemic Lupus Erythematosus: A Case for Initiating Trials

“…Our group is also investigating the impact of DNRAb on brain structure and function in patients with SLE with stable disease activity and without CNS disease. We found that these SLE patients demonstrate hypermetabolism on 18 F-fluorodeoxyglucose (FDG)-PET in the hippocampus, among other brain regions, and hippocampal hypermetabolism correlates with poor working memory (69), demonstrating that SLE patients with no other NPSLE symptoms may exhibit CD that correlates with clear abnormalities in brain function. Further, DNRAb antibody positivity was shown to correlate with hippocampal hypermetabolism (69) and decreased white matter microstructural integrity in the parahippocampal gyrus on DTI (67).…”

The Role of the Immune System in Autism Spectrum Disorder

“…In addition to the prenatal, maternal autoantibodies previously discussed, numerous studies have reported the presence of circulating anti-brain immunoglobulins in patients with ASD, as well as related conditions such as multiple sclerosis (Ryberg, 1982), schizophrenia (Henneberg et al, 1994), and systemic lupus erythematosus (SLE) (Libbey and Fujinami, 2010;Mackay et al, 2015;Suurmond and Diamond, 2015). Singer et al (2006) found that children with autism were more likely than their non-autistic siblings or controls to have serum that tested positive via western blot to fresh human brain samples (caudate, putamen, and prefrontal cortex).…”

Dynamic Contrast-Enhanced MRI Reveals Unique Blood-Brain Barrier Permeability Characteristics in the Hippocampus in the Normal Brain

“…4 Recent human studies in systemic lupus erythematosus correlated cognitive decline with region-specific abnormal findings in the hippocampus with FDG-PET. 5 Additionally, animal studies have revealed increased protein expression of CD36, matrix metalloproteinase-13, and osteopontin correlated with increased hippocampal BBBP, 6 and dynamic contrast-enhanced (DCE)-MR imaging-derived baseline contrast enhancement curves were highest in the hippocampi in control subjects. 7 The purpose of our study was to evaluate region-specific BBBP metrics in healthy human subjects.…”