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Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

Publication ,  Journal Article
Somarelli, JA; Mesa, A; Rodriguez, R; Avellan, R; Martinez, L; Zang, YJ; Greidinger, EL; Herrera, RJ
Published in: Lupus
March 2011

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein-protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.

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Published In

Lupus

DOI

EISSN

1477-0962

Publication Date

March 2011

Volume

20

Issue

3

Start / End Page

274 / 289

Location

England

Related Subject Headings

  • Ribonucleoprotein, U1 Small Nuclear
  • ROC Curve
  • Protein Structure, Tertiary
  • Principal Component Analysis
  • Peptides
  • Models, Molecular
  • Mixed Connective Tissue Disease
  • Lupus Erythematosus, Systemic
  • Humans
  • Ethnicity
 

Citation

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Somarelli, J. A., Mesa, A., Rodriguez, R., Avellan, R., Martinez, L., Zang, Y. J., … Herrera, R. J. (2011). Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease. Lupus, 20(3), 274–289. https://doi.org/10.1177/0961203310387180
Somarelli, J. A., A. Mesa, R. Rodriguez, R. Avellan, L. Martinez, Y. J. Zang, E. L. Greidinger, and R. J. Herrera. “Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.Lupus 20, no. 3 (March 2011): 274–89. https://doi.org/10.1177/0961203310387180.
Somarelli JA, Mesa A, Rodriguez R, Avellan R, Martinez L, Zang YJ, et al. Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease. Lupus. 2011 Mar;20(3):274–89.
Somarelli, J. A., et al. “Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.Lupus, vol. 20, no. 3, Mar. 2011, pp. 274–89. Pubmed, doi:10.1177/0961203310387180.
Somarelli JA, Mesa A, Rodriguez R, Avellan R, Martinez L, Zang YJ, Greidinger EL, Herrera RJ. Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease. Lupus. 2011 Mar;20(3):274–289.
Journal cover image

Published In

Lupus

DOI

EISSN

1477-0962

Publication Date

March 2011

Volume

20

Issue

3

Start / End Page

274 / 289

Location

England

Related Subject Headings

  • Ribonucleoprotein, U1 Small Nuclear
  • ROC Curve
  • Protein Structure, Tertiary
  • Principal Component Analysis
  • Peptides
  • Models, Molecular
  • Mixed Connective Tissue Disease
  • Lupus Erythematosus, Systemic
  • Humans
  • Ethnicity