To determine whether the agonistic activity of anti-PAD4 and anti-PAD3/4 antibodies differed based on anatomical site, IgG and IgA were co-purified from paired serum and sputum samples from representative anti-PAD-negative, anti-PAD4 mono-reactive, and anti-PAD3/4 cross-reactive RA or at-risk patient samples and tested for their ability to modulate PAD4 activity in vitro (Fig. 2c, d). The gene discussed is PADI3; the disease is rheumatoid arthritis.