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SSB/La or Sjögren Syndrome Antigen B or Lupus La protein is a human gene-encoded RNA-binding protein that is ubiquitous. It is essential to several metabolic steps in RNA – such as RNA processing, stabilization and folding. SSB/La is a complex protein involved in critical cell functions in RNA metabolism, immune function and epigenetic regulation. The immune system misperceives it and misrecognises it, resulting in autoimmune disorders such as Sjögren's syndrome and lupus.
SSB/La binds to the 3' ends of newly synthesized RNA polymerase III transcripts, such as precursor tRNAs, protecting them from exonuclease degradation. This activity ensures proper RNA maturation and processing. La functions as an RNA chaperone, assisting in the correct folding of certain mRNAs and other RNAs. This is crucial to RNA stability and function in the cell. Moreover, La protein can also bind to viral RNAs (including the one from hepatitis C virus) so that they are stable and translated in the host cell. Recent work has implicated SSB/La in X chromosome deletion (XCI), by attaching to Xist RNA, a long non-coding RNA that silences one of the X chromosomes in female cells. Knockdown of SSB/La leads to defects in XCI, indicating its crucial role in this epigenetic process.
SSB/La is an autoantigen associated with autoimmune diseases like Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Autoantibodies against La are commonly found in patients with these conditions. Anti-SSB/La is one of the common and important serologic features in SS. Overactive B cells and chronic lag in plasma cells result in a diverse set of autoantibodies. Autoantibodies that tend to be present ahead of disease manifestations are antinuclear antibodies (ANA), RF, anti-Ro/SSA, and anti-La/SSB. The earlier the antibodies are identified, the more anti-Ro/SSA antibodies in asymptomatic pregnant women can result in passive acquired autoimmunity in the infant (neonatopathic lupus syndrome, congenital heart block) due to transplacental transmission of the antibodies.
Figure 1. Schema depicting the effects of anti-SSB/La autoantibodies on neutrophil and macrophage functions, and autoimmunity
(Source: Yu C, et al. 2013)
Sjögren Syndrome Antigen B Antibody
Lupus La protein Antibody
References
1. Veenbergen S, et al. Autoantibodies in Sjögren's syndrome and its classification criteria. J Transl Autoimmun. 2021 Dec 27;5:100138.
2. Yu C, et al. Autoantibody profiling in systemic lupus erythematosus. Current Biomarker Findings. 2013 Aug;3:55.
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