Recent Developments in Biologic Therapies for the Treatment of Patients With Systemic Lupus Erythematosus

Pedro L. Carreira; David A. Isenberg


Rheumatology. 2019;58(3):382-387. 

In This Article


The pathogenesis of SLE involves genetic and epigenetic factors, environmental triggers and immunological abnormalities. These abnormalities include defective apoptosis and loss of tolerance; inadequate development of dendritic cells; defective function of regulatory T cells and B cells; defective B and T cells apoptosis and defective signalling pathways. Figure 1 shows the link between these factors and the sites of action of relevant therapeutic agents.

Figure 1.

Simplified diagram of SLE pathogenesis and site of action of therapeutic agents
Defective apoptosis results in production of uncleared nuclear material leading to dendritic-cells (DC) activation and BCR stimulation. DC will produce a number of cytokines, which will result in B-cell activation (BAFF and APRIL) but also differentiation of monocytes to macrophages (IFNα) that will present self-antigens to T and B cells but also produce cytocines. The activation of B cells needs a co-stimulatory signal between T-cell receptor (TCR) and MHC in antigen presenting cells (APC) but also CD40: CD40L binding with macrophage and dendritic cells. B-cells activation, differentiation, and proliferation leads to autoantibody production. Immune complex formation and tissue deposition results in organ damage. pDC: plasmacytoid dendritic cells; mDC: myeloid dendritic cells; fDC: follicular dendritic cells; BCR: B-cell receptor; BTK: Bruton's tyrosine kinase; BAFF: B cell activating factor; APRIL: a proliferation inducing ligand; APC: antigen presenting cells.