S100β is associated with cognitive impairment in childhood-onset systemic lupus erythematosus patients

Abstract

Objective To investigate serologic S100β protein levels in childhood-onset SLE patients (cSLE) and to elucidate their association with disease activity and neuropsychiatric (NP) manifestations. Methods We included 71 cSLE patients (67 females; median age 18 years; range 9-37 and 53 (47 females; median age of 20 years; range 6-29) age and sex matched healthy controls. Neurological manifestations were analysed according to the American College of Rheumatology (ACR) criteria. Cognitive evaluation was performed in all participants using Wechsler Intelligence Scale for Children (WISC-III) and Wechsler Adult Intelligence Scale (WAIS), according to age, and validated in Portuguese. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity (SLE Disease Activity Index (SLEDAI)), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and current drug exposures. Sera S100β protein levels were measured by enzyme-linked immunosorbent assay using commercial kits. Results The median S100β protein level was 116.55 pg/mL (range 1.53-468.50) in cSLE and 54.98 pg/mL (range 0.69-181.00) in healthy controls ( p < 0.001). An association was observed between S100β protein and NP manifestations ( p = 0.03). The S100β protein levels was associated with cognitive impairment in cSLE patients ( p = 0.006). Conclusions S100β protein levels are increased in cSLE with cognitive impairment. S100β may be considered a potential biomarker that underlies central nervous system (CNS) dysfunction, especially cognitive impairment.

Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions

“…Another potentially important mediator may be calcium‐binding protein S100ß, which is produced mainly by astrocytes. In low levels S100ß is neurotrophic, but overproduction by activated glial cells leads to loss of neuronal cells and increased permeability of the blood–brain barrier .…”

“…For example, neuron‐specific enolase, a neuronal glycolytic enzyme produced mainly by astrocytes, is increased in peripheral blood following acute brain injury but is decreased in chronic disorders such as dementia, multiple sclerosis, and NPSLE. Serum levels of S100ß are increased in adults and children with NPSLE . The lack of disease specificity of these biomarkers requires that their use be integrated with a priori decisions about attribution of NP events.…”

“…Concurrent measurement of biomarkers in CSF and peripheral blood could link neuroimaging abnormalities with laboratory variables that are relatively inexpensive and rapidly measured. The linking of neuroimaging abnormalities of blood–brain barrier permeability with elevated peripheral blood levels of MMP‐9 or S100ß could provide a convenient diagnostic tool and means of stratifying patients for clinical trials. Biomarkers of neuronal loss and reparative astrogliosis have been documented in CSF, and circulating levels of neurofilament light chain subunit (a component of myelinated axons) correlate with vascular , degenerative , and autoimmune inflammatory brain disease.…”

Lipocalin-2 is a pathogenic determinant and biomarker of neuropsychiatric lupus

“…Cluster 0 includes several enriched Gene Ontology (GO) terms involved in the immune response, including immune system processes (p<4.58×10 −6 ), cell adhesion (p<1.71×10 −4 ), leukocyte migration involved in the inflammatory response (p<1.88×10 −4 ), and response to interferon-gamma (p<1.71×10 −4 ). Another GO term of interest is S100b protein binding (p<3.62×10 −7 ), given that S100b is associated with cognitive impairment in SLE patients [50]. GO terms enriched in cluster 4 include other immune system processes (p<4.58×10-6), including several interferon response genes, leukocyte differentiation (p<4.43×10 −5 ), and regulation of cytokine production (p<1.54×10 −4 ).…”

Correlation of Serum BACE1 With Emergence Delirium in Postoperative Patients: A Preliminary Study

“…However, as a systemic inflammatory marker, IL-6 has little diagnostic value for ED. S100B is secreted by astrocytes and is a marker of cerebral inflammation; its expression level is related to cognitive changes associated with various diseases (Baptista et al, 2017;Lapa et al, 2017).…”