This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The long-term objectives of this prospective cohort study are to: (1) characterize the spectrum of nervous system (NS) involvement in patients with Systemic Lupus Erythematosus (SLE), a significant cause of morbidity in up to 75% of patients and (2) define important risk factors which may be unique for specifically targeted NS manifestations including stroke, cognitive dysfunction, and the psychiatric manifestations. Preliminary evidence suggests that frequency of stroke and other NS manifestations in our predominantly Mexican-American (MA) SLE population is high. The specific hypotheses which will be tested in this multi-year project are: (1) The risk of initial thrombo-occlusive events will be higher in SLE patients who have persistently abnormal levels of antiphospholipid (aPL) and anti-apolipoprotein H (anti-apoH) antibodies; (2) The development of cognitive dysfunction in SLE patients will be temporarily associated with abnormal levels of aPL and anti-apoH antibodies; (3) The development of psychiatric manifestations (psychosis, depression or anxiety) in SLE patients will be temporally associated with abnormal serum levels of anti-ribosomal P (anti-P); and (4) SLE disease activity, cumulative SLE-related organ damage or the presence of cardiovascular risk factors will all contribute to the risk of developing targeted NS manifestations in a way that is independent of aPL, anti-apoH or anti-P antibody status. RESEARCH PLAN: We will recruit SLE patients from the greater San Antonio area for enrollment into the study. Serial neurological, cognitive, psychiatric, rheumatological and immunological evaluations will be performed every four months and at the time of an end-point event for five years. METHODS: Kaplan-Meier Curves will be constructed comparing the time between thrombotic events in antibody positive and negative groups. Cox regression will be used to construct multivariate models to control for the effects of the potential confounders. Cognitive dysfunction will be measured as a continuous variable, with the fluctuations in functioning about the baseline for each patient compared with antibody levels. Close attention will be paid to the problems of multiple comparisons. An approach similar to that described for cognitive dysfunction will be used for psychiatric manifestations. CLINICAL
It has been estimated that up to 75% of patients with Systemic Lupus Erythematosus (SLE) experience some type of nervous system manifestations at some point in their disease course. This project will identify risk factors which may account for significant morbidity and provide crucial natural history data about SLE-related NS manifestations which are currently unavailable.
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