A number of studies have associated reduced serum amyloid P component (SAP)—a serum DNA binding and opsonizing protein—with the pathogenesis of systemic lupus erythematosus (SLE). New evidence from Zhang et al. suggests that SAP supplementation could enhance clearance of autoantigenic apoptotic material and ameliorate this disease.

In this study, immunization of mice with DNA led to the development of SLE-like disease. However, SAP binding to DNA increased phagocytic uptake of this material by macrophages and caused them to switch from a proinflammatory M2b phenotype observed with unbound DNA to an anti-inflammatory M2a phenotype. This was associated with decreased production of anti-DNA antibodies, IgG deposition in glomeruli, proteinuria and lupus nephritis. Furthermore, adoptive transfer of in vitro polarized M2a, but not M2b, macrophages attenuated disease to a similar extent as immunization with SAP bound DNA.

Zhang and co-workers also showed that IL-10 released by M2a cells is responsible for the inhibition of polarization to the M2b phenotype. Correspondingly, in vivo antibody blockade of IL-10 inhibited the protective effect of SAP binding to DNA.

“SAP supplements could complement insufficient DNA phagocytosis ability and regulate macrophage M2b-to-M2a switch in SLE ... which reveals a possible molecular mechanism for the modulation of macrophage differentiation and opens a new potential therapeutic avenue for SLE disease,” concludes Sidong Xiong, lead investigator of the study.