Clinical Information

The SS-A/Ro is part of the Ro/La heterogeneous antigenic complex which is made up of three unique proteins (52 kDa Ro, 60 kDa Ro and La) and four small RNA particles.(1,2) Unlike antibodies to SS-B/La that are less common, reported separately and mainly associated with a diagnosis of primary Sjogren’s syndrome, antibodies to SS-A/Ro are the most prevalent specificity among many autoimmune diseases such as primary Sjogren’s syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), rheumatoid arthritis (RA), and primary biliary cholangitis (PBC).(2-4) In addition, children born to mothers positive for anti-SS-A/Ro antibodies are at increased risk for congenital heart block.(3)

Historically, Ro52 and Ro60 autoantibodies were considered as a uniform autoantibody-system. Therefore, when anti-Ro52 or anti-Ro60 antibody is positive, the result was typically reported as anti-SS-A/Ro antibody positive.(4,5) However, recent studies have provided evidence that Ro60 and Ro52 are not part of a stable macromolecular complex and that anti-Ro52 and anti-Ro60 antibodies have different clinical associations with implications for diagnosis, prognosis and patient management.(4-6)

The Ro52 antigen is also known as TRIM21; this protein has E3 ligase activity and functions in the process of ubiquitination.(1-3) The Ro60 antigen is a 60-kDa RNA-binding protein known to have repair functions for misfolded RNA.(1-3)

Individuals positive for anti-SS-A/Ro antibodies may react with either Ro52, Ro60, or both antigens.(4-6) Patients with only anti-Ro52 antibodies display a higher incidence of IIM,SSc, or interstitial lung disease (ILD).(7). Anti-Ro52 antibodies, in conjunction with antisynthetase antibodies such Jo-1 (others include PL-7, PL-12, EJ, and OJ) are also highly associated with ILD in patients with IIM.(7,8) In contrast, isolated anti-Ro60 antibodies are associated with increased risk for SLE and, to a lesser degree, for SS.(8) Positivity for both anti-Ro52 and anti-Ro60 antibodies are most strongly associated with SS; this association is even stronger if anti-SS-B/La antibodies are also detected.(9) The presence of anti-Ro52 and anti-Ro60 antibodies may also be observed in patients with SLE.(10)