Biomarkers for CNS Involvement in Pediatric Lupus

Abstract

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population.

<p>Young Minds: Mental Health and Transitional Care in Adolescent and Young Adult Rheumatology</p>

“…32 Research is ongoing for reliable noninvasive biomarkers in this age group to determine whether anxiety and depression is specifically related to disease activity. 33 A systematic review by Quilter et al reported the prevalence of depressive symptoms in childhood onset SLE to be 6.7-59% and anxiety 34-37%. 13 In conditions such as SLE or other systemic vasculitides, as well as potential direct effects on the brain and nervous system caused by the condition itself, the impact of receiving a diagnosis such as these conditions and coming to terms with it, the relative rarity of the conditions, their potential severity, uncertainty of outcome and significant side effects of necessary drug therapy may all contribute to mental health in such young people.…”

Advances in the care of children with lupus nephritis

“…In recent years, the availability of powerful tools to scan both the genome and proteome have revolutionized and greatly accelerated biomarker discovery. Pediatrician scientists have embraced these tools for the study of cSLE (29)(30)(31)(32)(33)(34).…”

“…MCP-1 (monocyte chemoattractant protein) urinary levels can also predict improvement of renal disease (31). Despite high sensitivity and responsivity to LN activity, MCP-1, RANTES, and TWEAK lack specificity for LN, and have also been found in cerebral spinal fluid and linked to the development of central neuropsychiatric involvement in cSLE (33). NGAL is also a biomarker for acute kidney injury and MCP is for chronic kidney disease in patients without SLE.…”

The role of B cells and autoantibodies in neuropsychiatric lupus

“…However, a meta-analysis of a large cohort of lupus patients demonstrated that antiribosomal P antibodies were not related to any diffuse manifestations and possessed limited diagnostic value for focal elements of NPSLE [60]. Interestingly, the prevalence of anti-ribosomal P antibody in pediatric lupus (20–42%) is twice as that of adult patients (10–20%), indicating that the sensitivity of this biomarker may be age dependent [61]. Overall, as in the case of anti-NMDAR antibodies, the exact role of anti-ribosomal P antibodies in NPSLE remains inconclusive.…”

“…Interestingly, as is the case with anti-ribosomal P antibodies, anti-phospholipid antibodies are more prevalent in children with NPSLE compared to adults [61]. However, most of these studies fail to show a significant association between anti-β2 glycoprotein I antibodies and neuropsychiatric symptoms [62].…”