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Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading.

Publication ,  Journal Article
Scofield, RH; Kurien, BT; Ganick, S; McClain, MT; Pye, Q; James, JA; Schneider, RI; Broyles, RH; Bachmann, M; Hensley, K
Published in: Free Radic Biol Med
March 15, 2005

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. The Ro ribonucleoprotein particle, composed of a 60-kDa protein noncovalently associated with human cytoplasmic RNA, is the target of antibodies in 25-40% of lupus patients. Purified human 60-kDa Ro was found to be oxidatively modified. Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore we hypothesized that oxidation by-products, such as 4-hydroxy-2-nonenal (HNE), could lead to neoantigens like HNE-modified 60-kDa Ro, which could in turn initiate autoimmunity or drive epitope spreading. To test this hypothesis we immunized rabbits with either HNE-modified 60-kDa Ro or the unmodified Ro. Intramolecular epitope spreading within the Ro molecule and intermolecular epitope spreading to La, double-stranded DNA, nRNP, and Sm occurred preferentially in HNE-Ro-immunized animals. Nonspecific anti-HNE antibody, generated by immunization with HNE-keyhole limpet hemocyanin conjugate, did not significantly bind to these autoantigens. These data may suggest a hitherto unappreciated mechanism by which oxidative stress facilitates epitope spreading in SLE.

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Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

March 15, 2005

Volume

38

Issue

6

Start / End Page

719 / 728

Location

United States

Related Subject Headings

  • Time Factors
  • Ribonucleoproteins
  • Rabbits
  • RNA, Small Cytoplasmic
  • Proteins
  • Plasmids
  • Peptides
  • Oxygen
  • Oxidative Stress
  • Microscopy, Fluorescence
 

Citation

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Scofield, R. H., Kurien, B. T., Ganick, S., McClain, M. T., Pye, Q., James, J. A., … Hensley, K. (2005). Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading. Free Radic Biol Med, 38(6), 719–728. https://doi.org/10.1016/j.freeradbiomed.2004.11.001
Scofield, R Hal, Biji T. Kurien, Samantha Ganick, Micah T. McClain, Quentin Pye, Judith A. James, Rebecca I. Schneider, Robert H. Broyles, Michael Bachmann, and Kenneth Hensley. “Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading.Free Radic Biol Med 38, no. 6 (March 15, 2005): 719–28. https://doi.org/10.1016/j.freeradbiomed.2004.11.001.
Scofield RH, Kurien BT, Ganick S, McClain MT, Pye Q, James JA, et al. Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading. Free Radic Biol Med. 2005 Mar 15;38(6):719–28.
Scofield, R. Hal, et al. “Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading.Free Radic Biol Med, vol. 38, no. 6, Mar. 2005, pp. 719–28. Pubmed, doi:10.1016/j.freeradbiomed.2004.11.001.
Scofield RH, Kurien BT, Ganick S, McClain MT, Pye Q, James JA, Schneider RI, Broyles RH, Bachmann M, Hensley K. Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading. Free Radic Biol Med. 2005 Mar 15;38(6):719–728.
Journal cover image

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

March 15, 2005

Volume

38

Issue

6

Start / End Page

719 / 728

Location

United States

Related Subject Headings

  • Time Factors
  • Ribonucleoproteins
  • Rabbits
  • RNA, Small Cytoplasmic
  • Proteins
  • Plasmids
  • Peptides
  • Oxygen
  • Oxidative Stress
  • Microscopy, Fluorescence