Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies with nuclear antigen (nAg) specificity. Using (SWRxNZB)F1 (SNF1) mice, we showed higher levels of IgA production in the intestine and the nAg reactivity of fecal IgA under lupus susceptibility. Here, we determined if the fecal IgA abundance and nAg reactivity are higher in, different among, various lupus-prone preclinical models (MRL/lpr, NZBxNZW-F1, SNF1, NZM2410 and NZM2328). We also determined

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... f the fecal IgA nAg reactivity at pre-seropositive ages correlates with the eventual serum autoantibody levels in males and females of these mouse models. We show that age dependent increase in the abundance and nAg reactivity of fecal IgA can vary among different lupus-prone mouse models. Importantly, fecal IgA in these mice show significant levels of nAg reactivity, starting as early as at juvenile age. Furthermore, the pre-seropositive stage nAg reactivity of fecal IgA in most lupus-prone strains correlates well with that of eventual, seropositive stage systemic autoantibody levels. Gender differences in serum autoantibody levels were preceded by similar differences in the fecal IgA abundance and nAg reactivity. These observations suggest that fecal IgA features, nAg reactivity particularly, could serve as a biomarker for early prediction of the eventual systemic autoimmunity in lupus-prone subjects.