Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels

Systemic lupus erythematosus (SLE) is characterized by the production of anti-nuclear autoantibodies. Here, for the first time, we show that the abundances of gut permeability marker Zonulin and IgA1- and IgA2-subclasses are significantly higher in the fecal samples of SLE patients compared to HCs. Importantly, IgA-total, IgA1- and IgA2-subclasses from SLE patients showed higher nAg reactivity titers. Notably, we found that not only the nuclear antigen (nAg) reactive fecal IgA1:IgA2 ratio is higher in SLE patients, but also the abundance and nAg reactivity of fecal IgA and subclasses, IgA1 particularly, correlate with the fecal levels of Zonulin, which is produced primarily in the small intestine. These observations suggest that higher amounts of nAg-reactive IgA are produced, particularly, in the proximal gut as indicated by higher IgA1:IgA2 abundance and nAg reactivity ratios and correlation of these features with the Zonulin levels.