Patrolling Human SLE Haematopoietic Progenitors Demonstrate Enhanced Extramedullary Colonisation; Implications for Peripheral Tissue Injury

Abstract

Systemic Lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). By employing next-generation sequencing, we compared the gene transcription signatures of CD34+ HSPCs deriving from either the bone marrow or HSPCs patrolling the bloodstream of healthy and individuals with SLE, seeking common transcriptional pathways that may have been modified between steady and disease states. Our findings indicate that circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Non-mobilised, SLE-derived circulating HSPCs demonstrated enhanced engrafting and altered differentiation capacities. Importantly, xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. SLE CD34+ HSPCs homing and engraftment at extramedullary sites such as the spleen and kidneys may participate in peripheral tissue injury. Funding Information: This study was supported by the H2020-ERC-2016-ADG-LUPUSCARE-742390 and Greek State Scholarships Foundation (ΙΚΥ) MIS-5000432 and MIS-5001552 grants. Declaration of Interests: None. Ethics Approval Statement: Informed consent was obtained from all patients and human controls prior to sample collection (IRB protocol number 10/22-6-2017). All mouse animal work has been approved by the BRFAA ethics committee and the Attica Veterinary Department (758634/22-11/2019).