Perugino CA, et al. - Researchers investigated the antigenic trigger that drives the expansion of circulating plasmablasts and CD4⁺ cytotoxic T cells (CD4⁺ CTLs) in patients with IgG4-Related Disease (IgG4-RD). They used mass spectrometry, and sought to sequence Ig genes from single cell clones of dominantly-expanded plasmablasts and generate recombinant human monoclonal antibodies. They succeed at identifying relevant auto-antigens in IgG4-RD by affinity chromatography using patient-derived monoclonal antibodies. A subset of IgG4-RD patients had IgG4 galectin-3 autoantibodies, which showed correlation with galectin-3 plasma levels. Clinically observed marked elevations of circulating IgG4 and IgE were, at least in part, attributed to the development of IgG4 and IgE specific autoantibody responses.