The current study was initiated to address three hypotheses: 1) the gut microbiome composition differs among healthy controls, patients with asymptomatic or undifferentiated autoimmunity, and those with clinical SS or SLE; 2) the association between taxa and clinical autoimmunity status is modified by whether the individual has HLA SLE-risk alleles or not; and 3) the taxa associated with clinical autoimmunity status are associated with anti-SSA/Ro autoantibodies, and the magnitude of the effect is modified by the clinical status of the individual. Here, TRIM21 is linked to systemic lupus erythematosus.