Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a heterogeneous clinical presentation whose etiologies are multifactorial. A myriad of genetic, hormonal, immunologic, and environmental factors contribute to its pathogenesis, and its diverse biological basis and phenotypic presentations make development of therapeutics difficult. In the past decade, tens of therapeutic targets with hundreds of individual candidate therapeutics have been investigated.

Areas covered: We used a PUBMED database search through April 2020 to review the relevant literature. This review discusses therapeutic targets in the adaptive and innate immune systems, specifically: B cell surface antigens, B cell survival factors, Bruton's tyrosine kinase, costimulators, IL-12/IL-23, the calcineurin pathway, the JAK/STAT pathway, and interferons.

Expert opinion: Our ever-improving understanding of SLE pathophysiology in the past decade has allowed us to identify new therapeutic targets. Multiple new drugs are on the horizon that target different elements of the adaptive and innate immune systems. SLE research remains challenging due to the heterogenous clinical presentation of SLE, confounding from background immunosuppressives being taken by SLE patients, animal models that inadequately recapitulate human disease, and imperfect and complicated outcome measures. Despite these limitations, research is promising and ongoing. The search for new therapies that target specific elements of SLE pathophysiology are discussed as well as key findings, pitfalls, and questions surrounding these targets.

Keywords: Lupus; adaptive immune system; innate immune system; intracellular signaling; therapeutic target.