Immunology insights for rheumatologists & rheumatology professionals
“A fundamental event in the pathogenesis of systemic lupus erythematosus (SLE) is the formation of immune complexes with anti-nuclear antibodies (ANAs) and nuclear antigens, producing immune complexes that have immunological activity and can mediate local and systemic inflammation,” says David Pisetsky, MD, PhD, a professor of medicine and immunology at Duke University School of Medicine and a staff rheumatologist at the Durham VA Medical Center, both in Durham, N.C. “In addition to nephritis, these immune complexes can induce more generalized immune system disturbances.”
Dr. Pisetsky, the founding editor of The Rheumatologist, is the author of a review that is part of a series on immunology for rheumatologists launched earlier this year in Arthritis & Rheumatology (A&R).1 In this new installment, Dr. Pisetsky reviews the unique interplay between ANAs—antibodies to components of the cell nucleus—and nuclear molecules in the pathogenesis of SLE. The review also advances a model that can support research and the clinical management of SLE.2
“Furthermore, the article highlights the role of genetics in influencing these pathways,” Dr. Pisetsky says. “In addition to its relevance for studies on pathogenesis, the model on the interplay of anti-nuclear antibodies and nuclear antigens provides insights into the development of new biomarkers, as well as approaches to therapy.”
Dr. Pisetsky
Case Study
Dr. Pisetsky begins the review with a hypothetical patient case.
A 29-year-old African American woman presented with fatigue, arthralgias and difficulty thinking. The patient’s family history, clinical examination and laboratory findings are discussed in the review. A rheumatologist diagnosed SLE. After a month of prednisone treatment, antibodies to DNA were no longer detectable, and the complement level moved toward normal. The patient was referred to a nephrologist for a potential renal biopsy.
Next, the review covers the current SLE model. At the end of the review, Dr. Pisetsky refers back to the hypothetical patient case, citing its relevance to the model. The review includes an informative table, detailed figures and legends, and many references.
“Rheumatologists can benefit from the article [because] it provides an overarching model to understand the pathogenesis of SLE, as well as the basis for certain clinical manifestations,” Dr. Pisetsky says. “The article also provides an approach for interpreting laboratory findings when assessing disease activity and potential effects of therapy.”
SLE Model
The current model of SLE, which originated from the study of the lupus erythematous cell, includes the roles of ANAs, immune complex formation and complement binding. ANAs can “bind to DNA, RNA and protein complexes with nucleic acids,” Dr. Pisetsky writes.
