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The anti-Ro/SSA and anti-La/SSB antigen-antibody systems

INTRODUCTION

Autoantibodies directed against Ro/SSA and La/SSB autoantigens were originally identified in patients with Sjögren’s syndrome and systemic lupus erythematosus (SLE). Subsequent studies showed that anti-Ro/SSA antibodies may be present in patients with other autoimmune diseases, including systemic sclerosis, idiopathic inflammatory myopathies (IIM), primary biliary cirrhosis (PBC), and rheumatoid arthritis (RA). Additionally, anti-Ro/SSA antibodies (with or without anti-La/SSB antibodies) identify pregnant women who are at increased risk of having a child with neonatal lupus syndrome. Anti-Ro/SSA antibodies may also be the only autoantibodies present in a subset of patients with “ANA-negative” SLE. (See "Neonatal lupus".)

The anti-Ro/SSA and anti-La/SSB antibody system and the clinical significance of these antibodies are reviewed here. An overview of the antinuclear antibodies important in SLE and in related autoimmune diseases and the clinical significance of autoantibodies directed against double-stranded deoxyribonucleic acid (dsDNA), U1 ribonucleoprotein (RNP), Sm, and ribosomal P proteins are reviewed separately. (See "Measurement and clinical significance of antinuclear antibodies" and "Miscellaneous antinuclear antibodies" and "Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP" and "Antiribosomal P protein antibodies".)

Ro/SSA ANTIGENS

Serum containing autoantibodies directed against the Ro/SSA antigens may recognize one or both of two cellular proteins with molecular weights of approximately 52 and 60 kD [1-4]. These autoantigens are referred to as “Ro52” and “Ro60,” respectively. The two autoantigens were originally thought to interact with each other, but subsequent studies have shown that the two proteins reside in distinct cellular compartments, with Ro60 localized to the nucleus and nucleolus and with Ro52 localized to the cytoplasm.

Ro60 — The amino acid sequence of the Ro60 autoantigen was described in the late 1980s [1,2]; Ro60 was shown to bind small, non-coding ribonucleic acids (RNAs) termed “Y RNAs.” Although the function of Y RNAs is unknown, one report suggests that Y RNAs may be a source of micro (mi)RNA molecules, which have a role in the regulation of messenger (m)RNA stability and translation [5]. The crystal structure of Ro60 suggests that the protein can bind to both single- and double-stranded RNA. The protein may function as a “RNA chaperone” that binds to misfolded pre-5S ribosomal RNA and may hasten the degradation of the defective molecule. Ro60 may also bind to other cellular and viral RNAs in the cell, including Epstein-Barr virus (EBV) early RNA 1 (EBER1) [6]. Mice that lack the functional gene encoding Ro60 develop an autoimmune syndrome characterized by antiribosome and antichromatin antibodies, as well as glomerulonephritis [7], suggesting that Ro60 may have an important role in preventing systemic autoimmune disease.

Ro52 — The amino acid sequence of the Ro52 autoantigen was reported in 1991 [3]. Ro52 is an interferon-inducible protein that belongs to the “tripartite motif” family of proteins. Ro52 contains an amino (N)-terminal RING finger domain, followed by B-box and coiled-coil domains and by a carboxy (C)-terminal B30.2 or “PRYPRY” domain. The protein localizes to the cytoplasm and functions as an E3 ubiquitin ligase, an enzyme that adds ubiquitin molecules to target proteins [4].

               

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Literature review current through: Aug 2014. | This topic last updated: Jan 25, 2013.
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