Elsevier

Autoimmunity Reviews

Volume 2, Issue 5, September 2003, Pages 235-240
Autoimmunity Reviews

The anti-Sm immune response in autoimmunity and cell biology

https://doi.org/10.1016/S1568-9972(03)00018-1Get rights and content

Abstract

Anti-Sm antibodies are found in greater than 30% of the patients with systemic lupus erythematosus (SLE) and are diagnostic of SLE. The Sm autoantigens are the small nuclear ribonucleoprotein (snRNP) common core proteins. The seven core proteins, B, D1, D2, D3, E, F and G, shared by a majority of the snRNP particles, form a heptamer ring approximately 20 nm in diameter, with the snRNA passing through the center. The Sm epitopes are distributed on the outside surface of the ring. A repeated proline rich motif with homology to an Epstein bar nuclear antigen in the B protein and a gly–arg–gly motif including a symmetrical dimethylarginine post translational modification in the B, D1 and D3 proteins are major Sm epitopes. The anti-Sm response has features typical of an antigen driven immune response. SnRNP proteins share several characteristics with other autoantigens including their assembly into ribonucleoprotein particles, homologies to known viral proteins, presence of post translational modifications, a high abundance and great stability and the presence of repeated motifs. Current work on the snRNP particles is attempting to identify the features that predispose the common core proteins to become autoantigens in vulnerable individuals.

Section snippets

Detection of anti-Sm antibodies

Anti-Sm antibodies and antibodies against double stranded DNA are common anti-nuclear antibodies (ANAs) found in patients with SLE. The presence of ANAs is one of the 11 parameters used to identify SLE [2]. The presence of at least 4 of the 11 SLE parameters suggests a diagnosis of SLE. The clinical identification of the anti-Sm antibodies and other ANAs usually begins with immunofluorescence staining to identify antibodies that recognize nuclear antigens. This is typically done by indirect

The snRNP particles

The U1–U12 snRNP particles are designated by their snRNA components which range in size from 80 to 260 nucleotides. U1–U6 are the most abundant snRNP particles and U1 and U2 are present in approximately 1×106 copies per nucleus. The U1, U2, U4 and U5 snRNPs share the set of seven common core proteins, B, D1, D2, D3, E, F and G which are the Sm antigens and are designated the Sm class of snRNPs. In addition to the common core proteins each particle has several snRNP specific proteins (Fig. 1a).

The anti-Sm immune response

The anti-Sm autoimmune response is directed against multiple epitopes on the snRNP common core proteins. The B protein is the major antigen followed by the D1 and D2 proteins. The anti-Sm immune response displays the characteristics of a typical antigen driven response. The T cell epitopes supporting the response are specific to the snRNP core proteins and the anti-Sm Abs show evidence of affinity maturation [13], [14]. Because the snRNP particles is a large multi-protein complex, the B and T

Origins of the anti-Sm response

The etiology of lupus is unknown. A large number of genetic factors and several environmental factors are hypothesized as risk factors for the disease [19]. This suggests a variety of different paths can lead to lupus, thus it is a syndrome rather than a specific disease. However, in many lupus patients anti-Sm autoantibodies are generated. This suggests there are some unusual features of the snRNP particles that predispose them to becoming autoantigens in SLE. Comparisons with other

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