THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Study of B cells gives new insight into SLE, other diseases

Ignacio Sanz, MD
Ignacio Sanz, MD

Abnormalities and dysfunction in 
B cell regulation have long been recognized as a central feature of systemic lupus erythematosus (SLE). Less understood is what causes the dysfunctions seen in SLE and the roles that B cell dysfunction may play in other autoimmune diseases.

“B cells are a critical part of not only lupus, but a number of other autoimmune diseases,” said Ignacio Sanz, MD, Mason I. Lowance Professor of Medicine and Pediatrics, Chief of Rheumatology, Director of the Lowance Center for Human Immunology, and Georgia Research Alliance Eminent Scholar in Human Immunology at Emory University. “It is time for a state-of-the-art look at how B cells are involved in SLE and so many other important autoimmune diseases.”

Dr. Sanz will provide that overview during the Rheumatology Research Foundation’s Evelyn V. Hess, MD Memorial Lecture, from 1:00 – 2:00 pm Sunday in Room 6 C. While his presentation on Cellular and Molecular Basis of B cell Malfunction in Systemic Lupus Erythematosus: Implications for Disease Pathogenesis, Prevention and Treatment will focus on a single disease, there is every indication that unraveling the mechanisms that underlie the pathogenesis of lupus will provide insight into other diseases mediated by B cells.

Multiple molecular and genetic studies have shown that B cells in the setting of lupus are somehow more prone to activation, more prone to survival, and more prone to differentiating into antibody-producing plasma cells. Dr. Sanz’s lab has examined the prominent abnormalities of B cells and antibody production that are commonly seen in SLE. His work has focused on the characterization of antibody-secreting cells that occur during disease flares.

Research has used multidimensional flow cytometry to help identify specific subsets of B cells that are abnormal during lupus flare. Molecular analysis of those different subsets of abnormal B cells using different combinations of RNA sequencing, epigenetic profiling, and Next Generation Sequencing of the B cell repertoire helps isolate specific molecular programs and pathways that have gone awry.

The lecture will explore the origin and diversity of B cell populations in lupus, their different contributions to serum antibody production, and what is known of the molecular mechanisms that underlie their malfunction. Evidence grows about the role of epigenetic triggers and promotion of the abnormal development and regulation of both B cells and plasma cells in SLE.

“We know that every lupus patient is different and there is a strong sense that there are probably different subsets of lupus,” Dr. Sanz said. “It is entirely possible that patients in whom B cells have been abnormally activated through one pathway may be very different from patients whose B cells have been activated through some other pathway or mechanism.”

Understanding the cellular and molecular basis of autoantibody production in SLE is spurring new insight in the epigenetic regulation of abnormal B cell activity. The next step comes in applying those insights to target specific subsets of patients based on the different mechanisms that give rise to different variations in disease.

“It is also possible that there may be a subset of patients whose B cells are not all that abnormal and the error lies somewhere else,” Dr. Sanz said. “It could be that these patients maybe should not be treated with agents like rituximab that target B cells, but would respond better to some other agent. Understanding the heterogeneity of lupus could lead us toward more personalized treatments for different patients.”