Interestingly, free SC (ie, soluble pIgR) as well as SC-containing immunoglobulins can be found in the circulation, with increased levels both in symptomatic ACPA-positive pre-RA and at RA diagnosis.21 22 Together with the findings that the proportion of circulating IgA+plasmablasts was strikingly increased among seropositive at-risk subjects,23 it appears that mucosal antibody responses, and possibly transepithelial immunoglobulin transport, are increased prior to arthritis onset. The gene discussed is PRTN3; the disease is Arthritis.