Ro/SS-A and Systemic Autoimmune Diseases

Ro/SS-A is an autoantigen attributed to autoimmune conditions (sjögren's syndrome and systemic lupus erythematosus (SLE are two of the most common). The immune system in Sjögren's syndrome attacks the glands that secrete moisture, leaving the eyes and mouth dry. Ro/SS-A antibodies are found in 60-70 per cent of Sjögren's syndrome sufferers. These antibodies also appear in some individuals with SLE, and are related to some SLE symptoms such as SLE-associated photosensitivity in SLE-suffering mothers and neonatal lupus.

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Systemic Lupus Erythematosus

The chronic autoimmune disease systemic lupus erythematosus (SLE) can affect the skin, joints, kidneys, heart, lungs, and central nervous system. It involves an overactive immune system that produces antibodies against the body's own tissues, leading to inflammation and damage. The symptoms of SLE can vary and may include:

Neonatal Lupus Erythematosus

Neonatal lupus erythematosus (NLE) is a rare autoimmune condition, and most often affects newborns born to an autoimmune diseased (SLE) mother. Neonatal lupus erythematosus is almost caused by antibodies that the mother takes with her, via the placenta, and transfers to the child. Those antibodies are usually anti-SSA (Ro) and anti-SSB (La) antibodies. Symptoms of NLE may include:

Ro Complex

Ro complex is expressed in most tissues and cells (erythrocytes, platelets) but the shape and quantity vary with tissues, species, and embryonic stages. No one is sure what role it plays but the binding of Ro complexes to nucleic acids and the similarities with gene regulatory proteins point to RNA transcription. The Ro complex can also be moved to locations in the nucleoplasm and membrane regions where it normally isn't present, eg when the environment has an effect (eg, UV exposure, virus infection), leading to autoimmunity. Such antibodies are able to be passed onto the fetus through the placenta in pregnant women who already have active Ro/SS-A autoantibodies. That is, the fetus can arrive at birth with fetal heart block, liver damage, and thrombocytopenia from tissue damage from these antibodies.

Physiological Functions of Ro/SS-A Antigen

Ro/SS-A antigen is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). The two primary proteins that comprise the Ro/SS-A complex are Ro52 and Ro60. These proteins are located in both the nuclear membrane and the cytoplasm, where they perform essential cellular functions, including RNA binding and transcriptional regulation. Most patients with autoimmune disorders develop autoantibodies against Ro/SS-A antigens, which are valuable for diagnostic purposes. Additionally, Ro/SS-A can stimulate antibody production in B cells and play a role in the T-cell immune response. A malfunction in these immune cells may contribute to disease development.

Mechanism of Anti-Ro/SS-A

Anti-Ro/SSA can be used against Ro52 and Ro60 proteins. Anti-Ro/SSA has the greatest activity on the cell surface where Ro proteins are present on the cell surface and extracellular anti-Ro/SSA binds to Ro. Data also indicates that IgG isotypes of Anti-Ro/SSA antibodies penetrate into cells. Anti-Ro autoantibodies are commonly IgA, IgM, and IgG isotypes but there are typically 5 subclasses of IgG. The antibodies are produced using Ro peptides vaccination.

Anti-Ro/SSA is made in the cytoplasm of cells within the epidermis of the skin upon UV radiation. Ro antigens are elevated in the cell surface as well and anti-Ro/SSA antibodies mark cells for destruction. And anti-Ro52 antibodies have the strongest association with photosensitivity.

Several of the human MHC II (or HLA II, as we human types refer to it) alleles are linked to anti-Ro antibodies and the expansion of immune systems. Anti-Ro/SSA has genes with HLA II haplotypes HLA-DR3 and HLA-DR2 and with variants of HLA-DQ. T cells are drawn to MHC class II so T-cell response is beneficial in producing anti-Ro/SSA antibodies.

Conclusion

Anti-Ro/SSA antibodies are the most common anti-extractable nuclear antigen autoantibodies. Anti-Ro52 antibodies flare all forms of SLE, SSc, MCTD, RA and SS. Anti-Ro52 antibodies are pathogenic not just through direct tissue infection but also by disrupting Ro52 antigen activity. But more work on the Ro autoantigen-autoantibody network could provide new sources of autoimmune disease.

References

1. McCauliffe, D.; et al. Ro/SS-A and the pathogenic significance of its antibodies. Journal of autoimmunity. 1989, 2(4): 375-381.
2. Schulte-Pelkum, J.; et al. Latest update on the Ro/SS-A autoantibody system. Autoimmunity reviews. 2009, 8(7): 632-637.