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Blood Brain Barrier and Anti-NR2 Antibody in SLE Patients with Cognitive Dysfunction

Gulati, Gaurav
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427882673

Abstract Details

2015, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
BACKGROUND: Cognitive Dysfunction (CD) is one of the most common manifestations of neuropsychiatric SLE (NPSLE) and one of the most devastating. The pathogenesis of CD in SLE is not known, but in animal models, antibody to the NR2 subunit of the N-methyl D-aspartate receptor (aNR2) can cause memory impairment. However, this effect can only be demonstrated if the blood brain barrier (BBB) has been disrupted or if the antibody is introduced intrathecally. Several studies in SLE patients have failed to find an association of aNR2 with CD. None, however, has assessed the integrity of the BBB as a potential pathogenic cofactor. S100B protein is an astrocyte specific protein that has been used as biomarker of BBB disruption in traumatic brain injury and some neurodegenerative disorders. And, antibodies to this protein may indicate previous exposure to this immunologically privileged protein and might be used as an indicator of preceding BBB disruption. We hypothesized that aNR2 antibody is pathogenic in SLE patients only if there evidence of previous or ongoing BBB disruption as indicated by increased levels of S100B or anti-S100B. METHODS: Patients who fulfilled the revised American College of Rheumatology (ACR) criteria for SLE and were stable for at least 4 weeks were recruited from three different settings. Basic demographic, clinical and laboratory data was collected. The Automated Neuropsychological Assessment Metrics (ANAM), a computerized and validated tool, was utilized to measure cognitive function. The Total Throughput Score (TTS = number of correct responses/time) was used as the primary outcome measure. CD was defined as a score of less than 1.5 SD below the age, sex, and race matched RA population mean. Patients also had assessment of fatigue, depression, SLE activity and SLE damage using the FACIT fatigue score, Becks Depression Inventory (BDI), SLEDAI 2K, and SLICC respectively. Serum was analyzed by established ELISA techniques for anti-NR2 antibody, anti-S100B antibody and intact serum S100B protein. RESULTS: A total of 57 patients were evaluated. Twelve patients had CD. The age, ethnicity, and family income were significantly different between the two groups (p<0.05). In a multiple regression model adjusting for the above independent variables together with simple reaction time and opioid use, no significant effects of aNR2, S100B, or aS100B on decreasing TTS were found. And, when the effects of aNR2 antibodies were evaluated at high levels of S100B and aS100B, no significant influence on TTS was found. CONCLUSION: Serum antibodies to NR2 do not appear to play a role in the pathogenesis of CD in SLE even when analyzed in the context of BBB integrity. This would suggest that, if these antibodies are pathogenic, they are produced within the CNS and peripheral antibody measurements do not adequately reflect their intrathecal levels.
Erin Nicole Haynes, Dr.P.H. (Committee Chair)
Bin Zhang, Ph.D. (Committee Member)
Michael Luggen, M.D. (Committee Member)
31 p.
Surgery
Cognitive Dysfunction; SLE; ANAM; S100B; anti-S100B antibody; anti-NR2 antibody

Recommended Citations

Citations

  • Gulati, G. (2015). Blood Brain Barrier and Anti-NR2 Antibody in SLE Patients with Cognitive Dysfunction [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427882673

    APA Style (7th edition)

  • Gulati, Gaurav. Blood Brain Barrier and Anti-NR2 Antibody in SLE Patients with Cognitive Dysfunction. 2015. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427882673.

    MLA Style (8th edition)

  • Gulati, Gaurav. "Blood Brain Barrier and Anti-NR2 Antibody in SLE Patients with Cognitive Dysfunction." Master's thesis, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427882673

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.