Role of Complement in the Antiphospholipid Antibody Syndrome in Patients with SLE
Abstract
Antiphospholipid syndrome (APS) is a common, potentially life-threatening complication of systemic lupus erythematosus (SLE) that leads to venous/arterial blood clots and pregnancy loss. The most severe form of APS is known as catastrophic antiphospholipid antibody syndrome (CAPS) which is fatal in up to 50% of patients. How antiphospholipid antibodies (aPLs) cause blood clots and pregnancy loss is unknown. More importantly, there are no good treatments to reliably prevent blood clots and pregnancy loss in patients with severe APS and CAPS. We, and others, have shown that aPLs activate a portion of the immune system known as complement and that failure to regulate complement on the lining of blood vessels contributes to developing blood clots and pregnancy loss. Thus, drugs that inhibit complement are being proposed to prevent complications from APS/CAPS. The Principal Investigators (PIs) of this grant are at the forefront of studying complement biology and are authorities on the clinical development and use of a variety of approved, and soon to be approved, drugs to treat disorders caused by failure to regulate complement. The goal of this proposal is: (1) to use cutting-edge cellular and molecular assays to determine which SLE patients with aPLs are at greatest risk for blood clots as these will be the patients that are most appropriate for clinical trials of complement inhibitors and; (2) to determine, through the use of novel biomarkers, how long patients need to be treated. The PIs manage a large cohort of patients with SLE and APS; moreover, they have a record of accomplishment in translating novel laboratory findings into the clinic; thus, it is anticipated that we will be able to accomplish these studies in 30-36 months. On separate funding, the PIs are also developing a clinical trial for treating APS with the complement inhibitor (Ravulizumab) in the next 1-2 years. Thus, the impact of this proposal could be transformative for patients and ultimately contribute to the first approved drug to treat severe forms of APS/CAPS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110898
Entities
People
- Robert Brodsky
Organizations
- Johns Hopkins University
- United States Army