The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis

To describe a novel autoimmune system (Sa/anti-Sa) specific for rheumatoid arthritis (RA).

Antibodies were detected in immunoblots using human spleen and placenta extracts as antigens. Sera from 482 patients with various rheumatic diseases as well as from healthy controls were evaluated to define the disease associations of anti-Sa antibodies.

Sera from 88 of 206 (42.7%) unselected patients with RA recognized specific protein bands (the Sa antigen) in immunoblots of spleen or placenta extracts, including 9 of 31 (29%) patients seen in the first few months after disease onset. Anti-Sa antibodies were found both in rheumatoid factor (RF) negative (17/63 or 27%) and in RF positive patients with RA (71/143 or 50%). They were nevertheless absent in RF positive patients with other connective tissue diseases (0/39). Antibodies to Sa were essentially found in sera from patients with RA (specificity 98.9%) being found only in 3 patients whose arthritides did not fulfill the ACR criteria. The positive predictive value of anti-Sa antibodies for RA was 96.7%, while its negative predictive value was 69.8%. Anti-Sa antibodies were predominantly of the IgG isotype, with titers varying from 1/50 to > 1/1000. The Sa antigen was characterized as a poorly soluble protein that is present in normal human tissues and that is distinct from all previously described RA associated autoimmune systems.

Anti-Sa antibodies are a novel serological marker highly specific for RA. Since anti-Sa antibodies occur independently of RF, they can be used as an additional diagnostic tool. The molecular nature of the Sa antigen as well as its potential pathogenic role in a significant proportion of patients with chronic articular inflammation of the rheumatoid variety merit further definition.