Childhood-onset Systemic Lupus Erythematosus (cSLE) is an autoimmune disorder characterized by the production of autoantibodies directed at multiple organ systems. Neuropsychiatric disease is frequent in cSLE and studies demonstrate the prevalence of subtle neurocognitive deficits;however, predictors for patients at risk of developing severe disease and progressive impairment are not known. An association between antiphospholipid antibodies (aPLs) and neurocognitive impairment in adult-onset SLE has been demonstrated;however, the effects of aPLs on neurocognitive function in cSLE remain unknown. Our hypotheses are twofold: 1) Subjects with cSLE have neurocognitive impairment compared to a control group of non-diseased friends matched on age, educational level and socioeconomic status;and 2) cSLE subjects with aPLs have greater neurocognitve impairment than cSLE subjects without aPLs. We will recruit and follow a longitudinal cohort of 50 cSLE subjects and 50 non-diseased controls for three years. Utilizing both traditional neuropsychological tests and a shorter, computer administered neurocognitive assessment tool (the Pediatric Automated Neuropsychological Assessment Metrics), we will assess changes in neurocognitive function over time, controlling for confounding factors such as depression and disease activity. We observe that cSLE patients often experience school failure, and though their difficulties may be due to a combination of factors, we believe that the presence of neurocognitive deficits specific to cSLE are influential in the developing brain. The proposed study would be the first to follow a large prospective multiethnic cSLE cohort longitudinally to determine if disease activity and damage, specifically neurocognitive impairment, is related to aPL status. Childhood-onset Systemic Lupus Erythematosus (cSLE) is a serious, chronic yet understudied disease, more common in the African-American and Latino populations. Childhood-onset SLE impairs neurocognitive function that is essential for scholastic success and beyond, making childhood-onset SLE a significant public health crisis. In assessing this neurocognitive impairment, we will elucidate risk factors to target in future treatment and prevention trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AR053202-05
Application #
8120449
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Witter, James
Project Start
2007-09-15
Project End
2012-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
5
Fiscal Year
2011
Total Cost
$129,708
Indirect Cost
Name
Hospital for Sick Chldrn (Toronto)
Department
Type
DUNS #
208511808
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1-X8
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Levy, Deborah M; Peschken, Christine A; Tucker, Lori B et al. (2013) Influence of ethnicity on childhood-onset systemic lupus erythematosus: results from a multiethnic multicenter Canadian cohort. Arthritis Care Res (Hoboken) 65:152-60
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Möller, Jana C; Cron, Randy Q; Young, Daniel W et al. (2011) Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature. Pediatr Rheumatol Online J 9:5
Williams, Tricia S; Aranow, Cynthia; Ross, Gail S et al. (2011) Neurocognitive impairment in childhood-onset systemic lupus erythematosus: measurement issues in diagnosis. Arthritis Care Res (Hoboken) 63:1178-87
Levy, Deborah M; Bingham, C April; Kahn, Philip J et al. (2010) Favorable outcome of juvenile dermatomyositis treated without systemic corticosteroids. J Pediatr 156:302-7

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