ABSTRACT Understanding Systemic Lupus Erythematosus (SLE) presents a formidable challenge to both the basic scientist and the clinician, given its undulating and often unpredictable course, variability among different racial/ethnic groups, and dearth of approved medications. The Clinical Core of the Translational Center of Molecular Profiling in Preclinical and Established Lupus will be the foundation for three Research Projects that focus on molecular comparisons and contrasts between clinically asymptomatic and symptomatic autoimmunity to elucidate protective, inciting, and perpetuating events in the pathogenesis of SLE. The Clinical Core will leverage access to two unique sources of patient material: 1) the Research Registry for Neonatal Lupus (RRNL), which provides a rare opportunity to study asymptomatic women at risk for developing SLE who are identified to have anti-Ro antibodies solely based on the diagnosis of neonatal lupus in an offspring; 2) the NYU Lupus Cohort, a large well-characterized prospective multiracial/ethnic cohort; and 3) healthy controls age, ethnically/racially, and gender matched to subjects. The Clinical Core will provide detailed phenotypic analysis of these two cohorts by linking clinical data inclusive of validated disease activity and flare instruments specific to Lupus to precisely define timing of flares and remissions with biologic inquiries related to genetics, the microbiome, B and T cells, and autoantibody profiles. These goals will be accomplished via three specific aims: Specific Aim 1 will develop and maintain a clinical database and linked sample repository comprised of mothers enrolled in the RRNL and a prospectively followed cohort of subjects with overt SLE. Clinical data will be matched with subject blood and stool samples (specific to the needs of the Research Projects), which will be stored and maintained by the Clinical Core. Specific Aim 2 will establish a workflow for the delivery of specimens and linked clinical data to investigators in Projects 1, 2, and 3 with sample procurement coordinated to provide both fresh and stored specimens driven by the research protocols. Specific Aim 3 will incorporate appropriate statistical resources to perform analyses correlating research data with matched clinical data. It is anticipated that the Clinical Core will provide an unprecedented platform upon which state-of-the-art technologies can be applied to precisely phenotyped and longitudinally followed cohorts.