Clinical Information

Sjogren syndrome (SjS) is a heterogeneous systemic autoimmune rheumatic disorder characterized by diverse immunologic responses to SS-A/Ro and SS-B/La antigens.(1) These immune reactivities have been implicated in the destruction of exocrine gland epithelium with demonstration of typical peri-epithelial lymphocytic infiltration, which can vary from sicca syndrome to systemic disease and lymphoma.(2) The SS-A/Ro and SS-B/La system is considered to be a heterogeneous antigenic complex made up of three different proteins (Ro52, Ro60 and La) and four small RNA particles.(1,2) The SS-B/La antigen is a 48 kDa phosphorylated protein that can be found in the nucleus and the cytoplasm and binds to several RNA molecules.(3) SS-B/La appears to be susceptible to proteolysis and degrades into smaller, but immunoreactive, polypeptides.(4)

Unlike antibodies to SS-A/Ro, which are present in SjS and other connective tissue diseases (CTD; systemic lupus erythematosus, systemic sclerosis, inflammatory myopathies, overlap CTD) and primary biliary cholangitis, anti-SS-B/La antibodies are found primarily in patients with SjS.(2,5,6) In addition, SS-A/Ro antibodies may be found alone in many patients with SjS; however, anti-SS-B/La autoantibodies without SS-A/Ro have limited significant association for SjS diagnosis or phenotypic categorization.(2,6,7) Lastly, testing for anti-SS-A/Ro antibodies is included in the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary SjS; whereas, evaluation of anti-SS-B/La antibodies is not required.(8) In a recent multicenter study of more than 10,500 patients with primary SjS, anti-SS-B/La antibodies were detected in 58% of anti-SS-A/Ro antibody-positive cases.(9)

SS-A/Ro is an extractable nuclear antigen composed of two distinct antigens of 52 kDa (Ro52) and 60 kDa (Ro60) combined with cytoplasmic RNA species.(10-12) SS-A/Ro (Ro52 and/or Ro60) antibodies occur in patients with several different connective tissue diseases including SjS, an autoimmune disease that involves primarily the salivary and lachrymal glands, systemic lupus erythematosus (SLE), rheumatoid arthritis, systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM).(10-14) SS-A/Ro antibodies are associated with childhood SLE, neonatal SLE, and with congenital heart block in infants born to mothers with SLE.(12,14)

Traditionally, anti-Ro antibodies were detected by indirect immunofluorescence assay on HEp-2 substrates and confirmed by immunodiffusion, immunoblot, or enzyme-linked immunosorbent assay (ELISA), mostly using a mixture of both Ro52 and Ro60 as the antigens.(10) With technological advances in the expression and purification of recombinant proteins, solid-phase immunoassays that allow the separate detection of anti-Ro52 and anti-Ro60 antibodies, such as ELISA, fluorometric enzyme-linked immunoassays (FEIA), chemiluminescence immunoassays (CIA), addressable laser bead immunoassay (ALBIA), particle-based multianalyte technology (PMAT), or autoantigen arrays, became available.(11,12) Based on separate determination of Ro52 and Ro60 antibodies, there is substantial evidence that differential associations of these autoantibodies in patients may corelate with specific phenotypes in SLE (neonatal lupus, and fetal atrioventricular blockade), SjS, SSc, IIM, or primary biliary cholangitis.(10-13,15) Patients who have SjS with antibodies to both Ro52 and Ro60 are characterized by higher prevalence of markers of B-cell hyperactivity and glandular inflammation compared to those with single positivity.(13,15) Although these antibodies are often found together, both autoantibodies have important and distinct diagnostic and predictive attributes and should be distinguished when SS-A/Ro antibody is positive or tested singly.(11,13,15)

Like anti-Ro52 and anti-Ro60 antibodies, anti-SS-B/La autoantibodies are detected using a variety of solid-phase (such as plate, bead or membrane) immunoassays, such ELISAs, FEIA, CIA, ALBIA, PMAT, and dot or line immunoassays.(16)

For more information see Connective Tissue Disease Cascade.