Systemic lupus erythematosus (SLE) is an autoimmune disease where autoantibody formation and complement activation contribute to inflammatory damage in many organ systems. SLE affects women more often than men. Disease activity often increases at times the levels of sex hormones change: puberty, pregnancy, the post-partum period, and the use of hormone contraceptives. Therefore, estrogen is assumed to be an important factor in SLE expression, though proving the link between estrogen and disease activity has been difficult, as has defining the mechanism for increased SLE risk and disease activity in females. Because most females with SLE are sexually mature, clues to the hormonal triggers important in SLE pathogenesis are obscured by normal adult hormone production. Girls with SLE who are entering puberty should be an informative population for the study of these questions. In puberty, hormones that differ between sexes undergo the greatest change. Because SLE is rare in preteens, it has been hard to study children with early onset SLE until now. CARRA, the Childhood Arthritis and Rheumatology Research Alliance, is a network of allied North American pediatric rheumatology investigators. We propose to examine how the hormones that differ most between girls and boys at puberty (leptin, estrogen, and prolactin) affect development of autoantibodies in a cohort of children with SLE from CARRA centers. We will use antiphospholipid antibodies as a model system to study autoantibody acquisition in puberty, and to study how hormones affect autoantibody titer, specificity, and ability to activate complement. This small grant (R03) will (1) demonstrate feasibility of the collaborative study design, (2) produce preliminary data to support our hypotheses, (3) identify the most important hormones to study in puberty, and (4) estimate variance in the data studied in this population. The data from this study will allow us to estimate sample size and perform power analyses for a larger study utilizing all CARRA centers. ? ?
|Sestak, Al; O'Neil, K M (2007) Familial lupus and antiphospholipid syndrome. Lupus 16:556-63|