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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2022-09, Vol.242, p.109107-109107, Article 109107
• Main Authors: Gudi, Radhika, Kamen, Diane, Vasu, Chenthamarakshan
• Format: Article
• Language: English
• Subjects: Antigens, Nuclear; Biomarkers; Feces; Humans; Immunoglobulin A; Intestinal inflammation markers; Lupus Erythematosus, Systemic; Nuclear antigen; Permeability; Systemic lupus erythematosus
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2022.109107

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, and 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 that higher amounts of nAg-reactive IgA and gut permeability marker are produced, particularly, in the proximal gut suggest a compromised epithelial barrier function and pro-inflammatory characteristics of small intestine in SLE patients. •Levels of gut permeability marker, zonulin are higher in stool samples of lupus patients.•Fecal IgA-total and IgA-subclass levels are higher in SLE patients and the IgA levels correlate with the SLEDAI scores.•Fecal IgA and its IgA subclasses in lupus patients show higher nuclear antigen (nAg) reactivity.•Fecal IgA abundance and nAg reactivity in SLE patients correlate with zonulin indicating inflamed small intestine.•Higher fecal IgA1:IgA2 abundance and nAg reactivity ratios in SLE patients suggestmore nAg reactive IgA - production in the proximal gut.