Autoantibodies to nuclear antigens contribute to pathology in systemic lupus erythematosus (SLE). However, it is not understood how different isotypes of these antibodies contribute to disease. Here, Waterman et al. characterized circulating immunoglobulin A1 (IgA1) autoantibodies in individuals with SLE, showing that they reacted against many of the same self-antigens as their immunoglobulin G (IgG) counterparts, including against Smith ribonuclear proteins. The authors further showed that interferon-α (IFN-α)–producing plasmacytoid dendritic cells expressed the IgA1 receptor, Fc α receptor (FcαR), and that IgA1-containing immune complexes could drive IFN-α production by these cells in vitro. The authors showed that these responses required the presence of both IgA1 and IgG. Last, the authors showed that, in 18 individuals with SLE, interferon-stimulated gene expression positively correlated with the amount of FcαR in whole blood. Together, these results suggest that targeting FcαR could be a potential therapeutic for SLE treatment. —Brandon Berry
