Analysis of the Human B Cell V(D)J Repertoires from High-Throughput Sequencing in SLE and SLE-Associated Nephritis Patients

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease with various presentations which can become fatal. Lupus nephritis (LN) develops from SLE and is a chronic inflammatory disease that affects the kidneys in about 50% of patients. It is amongst the most severe sequelae of SLE, and substantially contributes to morbidity and mortality. Despite advances in its management, little progress has been made with respect to the adverse outcomes. We aim to analyze the human B cell V(D)J repertoires retrieved from high-throughput sequencing of immunoglobulin (Ig) genes amplified from samples of SLE and SLE associated nephritis patients, and compare them to those of healthy controls. This can shed light on the dynamics of Ig affinity maturation in SLE autoimmunity.

B cell populations were sorted from SLE and SLE-associated nephritis patient peripheral blood and bone marrow samples as well as from healthy controls; mRNA were extracted, and Ig genes amplified and sequenced. Sequences were pre-processed using pRESTO, annotated using IMGT/HighV-QUEST, graphed for the distribution of B cell populations using a custom R script, and assigned clones using Change-O. Lineage trees were constructed using IgTree©. Overall, 41,974,736 assembled sequences were analyzed in this study. Results from repertoire analysis of these clones will be presented.