SSa (Ro) Antibodies in Sjogren's Syndrome, Lupus, and Pregnancy

SSa (Ro) antibodies are found in Sjogren's, lupus, and related disorders. In pregnancy, SSa antibodies increase the risk of neonatal lupus and heart block.

By Elaine Moore

SSa antibodies are autoantibodies, which means that they target the body’s own proteins rather than infectious or other foreign protein antigens. Patients with autoimmune connective tissue diseases such as lupus produce autoantibodies directed against a wide variety of cellular components including nucleic acids, mitochondria, cell-surface antigens,and ribonucleoproteins. A small cellular RNA-protein complex known as Ro/SSA has been found to react with SSa (Ro) antibodies from many patients with system lupus erythematosus (SLE), Sjogrens syndrome and related disorders.

Clinical studies also suggest that 70 percent of patients with SSA antibodies also have rheumatoid factor (RF). Rheumatoid factor is an autoantibody that targets immunoglobulin G, which is present in rheumatoid arthritis (RA), Sjogren’s syndrome, and occasionally scleroderma and polymyositis. RF is also seen in the rheumatoid arthritis overlap syndromes, such as RA/SLE overlap and Scleroderma/RA overlap. RF precipates with immunoglobulins to form deposits in joints, causing symptoms of arthritis.

SSa Antibodies With a Negative ANA Test Result

Although they’re primarily considered a type of antinuclear antibody (ANA), SSa antibodies can target nucleic acids in the cell cytoplasm rather than the cell nucleus. ANA target nucleic acids in the cell nucleus. For this reason, SSa antibodies are often seen in individuals who have negative ANA tests. Individuals with ANA-negative systemic lupus frequently have SSa antibodies.

This is also the case in Sjogren’s syndrome where more than 75 percent of people with have SSa antibodies, but only 40-70 percent of patients test positive for ANA. In the clinical laboratory, the most sensitive blood tests for SSa include ELISA and Western blot immunodiffusion tests.

SSa Antibodies in Connective Tissue Disorders

SSa can be used as diagnostic markers, helping with the diagnosis of various autoimmune disorders. SSa also contribute to disease pathology. SSa (Ro) antibodies are primarily seen in Sjogren’s syndrome where they’re usually accompanied by SSb (La) antibodies. SSa antibodies are also seen in 30-40 percent of systemic lupus erythematosus (SLE) cases, and 5-10 percent of individuals with progressive systemic sclerosis (PSS) and 5 percent of individuals with polymyositis.

Studies indicate that the persistent presence of SSa antibodies can occur in static disease but is more often seen in progressive disease. A 10-year follow-up study conducted by researchers at Johns Hopkins University showed that 65 percent of patients with lupus/Sjogren’s overlap syndromes with SSa antibodies had a more progressive disease course. In addition, 25 percent of these patients showed evidence of progressive arthritis, renal disease, interstitial pulmonary disease, central nervous system disease and vasculitis.

In patients with SLE, SSa autoantibodies also suggest a progressive disease course. In SLE, SSa antibodies have been closely associated with the development of nephritis, vasculitis, lymphadenopathy, and leucopenia. Anti-SSa antibodies are also seen in subacute cutaneous lupus erythematosus, the neonatal lupus syndrome, and in the Sjögren's syndrome/lupus erythematous overlap syndrome. SSa antibodies are especially common in the form of discoid lupus called chilblain lupus erythematosus, a skin condition that causes reddened lesions and photosensitivity.

SSa in Pregnancy and in Neonates

In pregnancy, SSa antibodies can have severe consequences for both the mother and neonate. In pregnant women, SSa antibodies put the fetus at high risk for developing complete congenital heart block, a potentially fatal complication of the disorder known as neonatal lupus syndrome. Neonatal lupus syndrome is also associated with the development of thrombotic thrombocytopenic purpura, a potentially fatal condition of low platelets causing abnormal blood clotting.

Although random maternal screening for possible SS-A antibody positivity and potential neonatal lupus syndrome is not warranted, pregnant patients with Sjogren’s syndrome or lupus should be tested for SSa antibodies.

Genetic Influences

The presence of anti-SSa antibodies is associated with the HLA-DR2 and HLA-DR3 phenotypes. Evidence suggests a relationship between women with SSa antibodies and HLA-DR3 antigens in that they have an increased frequency of HLA-DR3-linked B8, DQw2, and DRW52 phenotypes. The association of these markers to Sjogren’s syndrome and systemic lupus is driven by SSa antibodies rather than the connective tissue disorders. Individuals with SSa antibodies are immunogetically closely related even though they may have no symptoms or entirely different disease presentations.

SSa antibodies are present in low titers in about 15 percent of the normal population. Studies show that all HLA-DR3 anti-Ro(SS-A) antibody-positive women are at risk for giving birth to a child with neonatal lupus syndrome.

© 8 Nov 2010 Copyrighted by Elaine Moore

Resources:

Mark Mamula, Own Fox, Hajime Yamagata, and John Harley. May 16, 2010. The Ro/SSa Autoantigen as an Immunogen; Some Anti-Ro/SSa Antibody Binds IgG. accessed Oct 10, 2010.

E. Simmons-O’Brien, S. Chen, R. Watson, et al. 1995. "One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow up." Medicine. May; 74(3): 109-30.