B Cell-Depleting Therapy in SLE & Lupus Nephritis

“B cells are central orchestraters of autoimmune disease by contributing to autoantibody production, antigen presentation and cytokine production,” says Georg Schett, MD, head of the Department of Medicine 3 (Rheumatology and Immunology) of the Friedrich-Alexander University Erlangen-Nürnberg, Germany. “B cells can be inhibited by monoclonal antibodies and chimeric antigen receptor (CAR) expressing cells.”

Dr. Schett is the corresponding 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. Schett and coauthors discuss the functional aspects of antibody- and cell-based B cell-depleting therapy in systemic lupus erythematosus (SLE).²

B Cell Insights

The generation of autoantibodies by B cells is fundamental in the pathogenesis of SLE, the authors write. After B cells differentiate in the bone marrow, they populate the spleen and lymph nodes, undergoing further maturation to become memory B cells, antibody-producing plasmablasts and plasma cells. Targeting B cells is essential in the treatment of such autoimmune diseases as SLE, in which B cell tolerance is disrupted, leading to the development of autoimmune B cells and autoantibodies.

The authors introduce the review with a patient case study illustrating chimeric antigen receptor (CAR) T cell treatment for SLE. Next, the review examines the immunopathology of SLE, followed by a discussion of how B cells trigger physiologic and pathologic humoral immune responses. The authors discuss lessons from antibody-mediated therapeutic B cell targeting and deep B cell depletion via CD19 CAR-T cells in SLE, and cellular sources of antibody production by CAR-T cells. Lastly, the review returns to the patient case study, discussing the tolerability of B cell depletion in autoimmune disease.

The review includes detailed figures and legends, and many references.

Example Case

The review describes a 32-year-old white woman diagnosed with SLE when she is 33 weeks pregnant. The patient presents with pericardial effusion, proteinuria, thrombocytopenia and anemia. Dysarthria and ataxia with isolated white matter lesions on magnetic resonance imaging suggest cerebral involvement. Serology is positive for anti-nuclear antibodies and highly positive for anti-double-stranded DNA antibodies and complement consumption. The SLE Activity Index is high. Initial treatment includes glucocorticoids and hydroxychloroquine.

After lupus nephritis is diagnosed via biopsy, the patient receives mofetil treatment, which is ineffective in achieving remission, as are tacrolimus, belimumab, cyclophosphamide and rituximab.

The review discusses the patient’s signs and symptoms, which indicate an active, treatment-refractory state. After the conduction of CD19 CAR-T cell treatment, which is described in detail, disease activity improves rapidly and the patient’s symptoms resolve. The principle and main outcomes of CAR-T cell treatment are demonstrated in a detailed figure.