Autoantibodies recognising this antigen were first described in Sjögren’s syndrome (and were assigned the term SS-A). In Sjögrens syndrome the autoantibodies are frequently detected in association with autoantibodies to La antigen (SS-B). The anti-Ro antibody has been subsequently detected in the sera of many patients suffering from a variety of autoimmune diseases. There are several clinical associations between anti-Ro antibody and certain systemic rheumatic diseases, particularly Sjögrens syndrome and SLE. Anti-Ro antibodies are often found together with anti-La. However, anti-Ro antibodies alone are often found in lupus, particularly in limited forms of the disease. There seems to be a close association between the presence of this antibody and photosensitivity. Anti-Ro often appears before anti-La. Anti-Ro (with or without La) are found in pregnant women exhibiting congenital heart block in their fetus. Most of these women will have no indication of lupus at the time. Anti-Ro antibodies are present in the majority (>60%) of so called anti-nuclear antibody negative lupus patients because Ro is poorly detected by immunofluorescence in tissues or in cell lines. The use of the Hep2000 cell line which contains transfected Ro decreases the likelihood of missing anti-Ro considerably. The Ro antigen was originally thought to be cytoplasmic but subsequently it was found to be present in nuclei as ribonuclear protein complexes with small RNAs. These ribonuclear complexes shuttle between the nucleus and the cytoplasm during the cell cycle.
Ro antigenic epitopes from most tissues are on two proteins; Ro60 and Ro52. Most positive sera recognise both forms, often together with La.
The Hep2000 cell line is transfected with Ro60. The ENA screen and the anti-Ro specific assay that we use contains both Ro 52 and Ro60. A very small number of patients, particularly with subacute cutaneous lupus, have antibodies only to Ro52. These may be ANA negative though ENA positive.
The full significance of detection of anti-Ro52 alone is not yet clear. Ro52 may be one of the first autoantibodies to develop in connective tissue disease. It is often found with Jo1 or Scl70 and patients with myositis or scleroderma. Patients with anti-Ro 52 alone at first investigation often develop anti-Ro60 anti-La or other ENAs as disease progresses. Recently the possibility of anti Ro52 alone in autoimmune liver disease has been observed.
Autoantibody associated with SLE or Sjögren’s syndrome.
Anti-Ro antibodies are found in 60 to 90% of patients with Primary Sjögrens syndrome and 30 to 40% of patients with SLE who appear to fall into specific subsets. Anti-Ro antibodies are found in the majority of patients with secondary Sjögrens syndrome whatever the primary disease. In SS, anti-Ro (usually associated with anti-La) has been related to manifestations such as vasculitis, anaemia, thrombocytopaenia and lymphopaenia. In SLE it has been associated with photosensitive skin rash, pulmonary disease and lymphopaenia. It is found in 50% of lupus patients with complement (C2 or C4) deficiency and 75%-90% of patients with subacute cutaneous lupus erythematosus. Levels do not correlate with disease activity. In SLE anti-Ro is not always associated with anti-La.Of particular importance is neonatal lupus erythematosus (including complete congenital heart block) where affected neonates have anti-Ro and anti-La antibodies. Complete congenital heart block can occur in babies of mothers who are subsequently shown to be Ro positive but who show no signs of autoimmune disease. Conversely, only around 1 in 50 babies born to mothers who are Ro positive will develop heart block.
Fluorescence enzyme linked immunoassay (Phadia Immunocap 250): Human recombinant Ro52, Ro60 proteins IgG antibodies
Test is only carried out when ENA screen is positive.
Results reported as negative, equivocal or positive.
5 – 7 days
Immunology The James Cook University Hospital