Table 2 Factors suggesting autoantibodies and ICs involved in the pathogenesis of Sjögren’s syndrome (SS)

• Female preponderance (i.e., estrogen’s central role in increasing autoantibodies)

• Women respond to infection, vaccination, and trauma with more antibodies compared to men

• Autoantibodies (i.e., Ro/SSA and La/SSB) part of SS classification criteria

• B/plasma cells in salivary glands of SS patients release Ro/SSA and La/SSB, which are ANA-type autoantibodies

• B cell hyperactivity (i.e., hypergammaglobulinemia) found in SS patients

• Pregnancy increases the risk for SS in young women; estrogen with prolactin increases Ro/SSA and La/SSB autoantibodies

• Some studies report more autoantibodies in women with SS compared to men

• Rheumatoid factor (RF), which forms ICs, present in 60–80 % of SS patients

• RF predicts severity of SS

• Elevated IgA in SS patients binds RF to form ICs and damage salivary glands

• Genetic predisposition in SS patients: low copy number of the IgG receptor FcγRIIIb gene FCGR3B reduces clearance of ICs

• B cells are activated by TLRs and BAFF on their surface; TLRs and BAFF correlate with autoantibody levels in SS patients

• IC deposition in salivary glands activates TLRs on epithelial cells generating the “IFN signature” that is associated with SS pathology

• Viral infections suspected in “triggering” SS activate TLRs to produce “IFN signature” as well as strongly inducing IC formation

• ICs known to produce tissue pathology by increasing inflammation, fibrosis, and apoptosis—endpoint characteristic of SS

• SS in women is associated with other ADs that occur predominantly in women like RA, thyroiditis, and Raynaud’s phenomenon—diseases where autoantibodies and ICs are believed to promote disease pathology