Anti-SSA/Ro autoantibodies

In 1969, two separate labs simultaneously identified antigens in the sera of SLE and SS patients. Clark et al. referred to the antigen as Ro – named after the patient from which the antibodies were extracted, while Alspaugh & Tanand used the term SSA. It was later found that the labs described the same antigen, hence the compound term for the antibody, Anti-SSA/Ro, Anti-Ro/SSA. == Methods of detection ==

In laboratory settings, ELISA and immunodiffusion assays are most commonly used to detect levels of Anti-Ro/SSA antibodies in patient sera. Antibodies specific to Ro52 are difficult to detect via laboratory testing. Their low detectability may be attributed to several factors: the antibodies are precipitin negative, lack antinuclear antibody (ANA) specific fluorescence staining patterns, and have a low signature in ELISA assays. Furthermore, Ro52 can be masked by Anti-Ro60 antibodies in lab tests that simultaneously assess the two antibodies. == Mechanism ==

Anti-Ro/SSA can target Ro52 and Ro60 proteins. Most Anti-Ro/SSA activity occurs on the cell surface, wherein Ro proteins are expressed on the cell membrane and extracellular Anti-Ro/SSAs bind to Ro. There is some evidence that the IgG isotype of anti-Ro/SSA antibody can enter the cell. The mechanism that induces Anti-Ro/SSA production in autoimmune disorders remains under study. Some proposed factors that may stimulate production are viral infection, treatment of cells with TNF-α, cellular apoptosis, and exposure to UV irradiation. • Anti-Ro/SSA is produced in the cytoplasm of cells in the epidermal layer of the skin following UV irradiation. Ro antigens are simultaneously upregulated on the cell surface, resulting in the Anti-Ro/SSA antibody marking cells for destruction. Anti-Ro52 antibodies in particular have been tied to elevated photosensitivity. Certain alleles of the human major histocompatibility complex (MHC II, called HLA II in humans) have been associated with the presence of Anti-Ro antibodies and the spread of the immune response. Anti-Ro/SSA associates with the HLA II alleles HLA-DR3 and HLA-DR2, as well as some HLA-DQ alleles. The T-cell response plays a role in the formation of Anti-Ro/SSA antibodies due to T-cell affinity for MHC class II. == Antigens ==

The specific pathogenic role of the Ro antigen in autoimmune disorders remains unknown. Ro52 can both regulate and be induced by INF cytokines. Loss of function or blockage of Ro52 results in uncontrolled inflammation at the onset of injury or disease. Patients with SLE and SS not only show elevated levels of Anti-Ro antibodies, but also elevated levels of Ro52. Ro52 has one primary epitope to which anti-Ro/SSA binds, independent of the autoimmune disease. The most common domain anti-Ro52 targets is the coiled coil (cc) domain, as well as the RING and B-box domains. The absence of Ro60 results in an elevated immune response and decreased resilience to immune-related stress. The epitope of the Ro60 protein is similar to that of the Epstein-Barr virus, and the presence of the virus may enhance the autoimmune response to Ro60, as anti-Epstein Barr antibodies can target the protein. == In systemic lupus erythematosus (SLE) ==

Anti-Ro/SSA antibodies are found in 40–90% of patients with systematic lupus erythematosus (SLE). The antibodies can be detected years before symptoms of SLE surface, making them an effective diagnostic tool. In patients with SLE, high levels of Anti-Ro/SSA are correlated with elevated levels of IFN-α. The presence of Anti-Ro/SSA antibodies also correlates with symptoms of photosensitivity, cutaneous vasculitis, and hematological disorders. In individuals with cutaneous lupus erythematosus (CLE), a subcategory of lupus erythematosus, elevated levels of Ro52 are found regardless of expression of Anti-Ro autoantibodies. == In neonatal lupus erythematosus (NLE) ==

The presence of Anti-SSA/Ro in pregnant women with SLE is associated with an increased risk of neonatal lupus erythematosus which can be accompanied by congenital heart block (CHB) in the fetus. SLE-related symptoms in infants that arise from Anti-Ro/SSA resolve in about six months as the mother's antibodies leave the baby's system. ==References==