“Sex is another major genetic influence on pathogenesis that may reflect the effects of hormones and the number of X chromosomes and the pattern of X chromosome inactivation,” Dr. Pisetsky writes.
Case Review
The hypothetical patient showed features of the SLE model.
Along with both her sex and an African ancestry placing her at high risk, the hypothetical patient had evidence of a genetic predisposition based on her family history—a sister with rheumatoid arthritis and an aunt with lupus. She also had a cluster pattern of ANA expression associated with nephritis, along with anti-DNA antibodies and anti-RBP antibodies, which contribute to heightened immune activity and nephritis. Due to proteinuria, a renal biopsy would likely show evidence of immune deposition.
If treatment with a combination of glucocorticoid steroids and mycophenolate mofetil was effective, laboratory testing would show a decrease in anti-DNA antibody levels and an increase in complement levels, Dr. Pisetsky suggests.
He explains that SLE agents can be placed at key steps in the model. Specifically, “steroids can decrease inflammation and cytokine production; hydroxychloroquine can affect endosomal function and signaling by TLR-9; hydroxychloroquine may also affect the generation of NETs; mycophenolate can affect B cell function, as can belimumab; and rituximab can eliminate CD20+ B cells without effects on plasma cells. Anifrolumab can inhibit responses to interferon by blocking the receptor.” He adds that chimeric antigen receptor T cells could be considered to eliminate B cells if the patient is unresponsive to treatment.
Katie Robinson is a medical writer based in New York.
References
- Bucala R, Solomon DH. Immunology for the rheumatologist: A&R introduces a new problem-based immunology review series with great educational potential. Arthritis Rheumatol. 2024. Jan;76(1):9–10.
- Pisetsky DS. Unique interplay between antinuclear antibodies and nuclear molecules in the pathogenesis of systemic lupus erythematosus. Arthritis Rheumatol. 2024;76(9):1334–1343.
