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Rheumatology Advance Access originally published online on August 2, 2008
Rheumatology 2008 47(10):1587; doi:10.1093/rheumatology/ken300
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

LETTERS TO THE EDITOR

4-Hydroxynonenal-modified Ro 60 autoantigen accelerates autoimmunity in experimental animals

B. T. Kurien1 and R. H. Scofield1,2,3

1Arthritis and Immunology Program, Oklahoma Medical Research Foundation, 2Department of Medicine, University of Oklahoma Health Sciences Center and 3Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

Correspondence to: B. T. Kurien, Oklahoma Medical Research, Foundation, 825 NE 13th Street, MS 24, Oklahoma City, OK 73104, USA. E-mail: biji-kurien{at}omrf.org

SIR, We read with interest the review article entitled ‘Consequence of neo-antigenicity of the ‘altered self ’’ [1], where the authors discuss the importance of oxidation-specific protein adducts in plasma membranes. We would like to point out that we have also shown the importance of 4-hydroxynonenal (HNE), a lipid eroxidation by-product, modified Ro 60 (SS-A) autoantigen in the rapid development of autoimmunity in an animal model of SLE [2] and the role of oxidatively modified proteins in autoimmune diseases [3]. Ro 60 RNP is a common target of autoantibodies in both SLE and SS. This structure is made up of a 60 kDa protein non-covalently associated with at least one of four short uridine-rich RNAs (the hY RNAs) [3, 4]. These hY RNAs are also associated with the 48 000 molecular weight La (or SS-B) autoantigen. Anti-Ro is found in 25–40% of patients with SLE, while anti-La is found in substantially fewer patients [3, 4].

Tolerance against Ro 60 and other autoantigens was abrogated faster and strongly in the HNE-Ro 60-immunized animals compared with the Ro 60-immunuzed animals. Immunization with HNE-modified Ro 60 induced a rapid intramolecular epitope spreading (within the Ro 60 molecule) and a rapid inter-molecular epitope spreading to other autoantigens. Such a scenario envisages developing antibodies to 60 kDa Ro and thus autoimmunity to the entire Ro RNP particle after an initial immune response to oxidized Ro 60.

We studied oxidative modification of Ro 60 since we and others observed free radical mediated peroxidative damage in SLE and other diseases [5–9]. Significantly higher HNE-modified protein levels have been found to occur in children with SLE [7].

Thus, we believe that oxidative modification of proteins is important in the generation of autoantibodies and thus brings about autoimmunity.

Formula

Disclosure statement: The authors have declared no conflicts of interest.


   References
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 References
 

  1. Eggleton P, Haigh R, Winyard PG. Consequence of neo-antigenicity of the ‘altered self’. Rheumatology (2008) 47:567–71.[Abstract/Free Full Text]
  2. Scofield RH, Kurien BT, Ganick S, 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) 38:719–28.[CrossRef][Web of Science][Medline]
  3. Kurien BT, Hensley K, Bachmann M, Scofield RH. Oxidatively modified autoantigens in autoimmune diseases. Free Radic Biol Med (2006) 41:549–56.[CrossRef][Web of Science][Medline]
  4. O’Brien CA, Wolin SL. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes Dev (1994) 8:2891–903.[Abstract/Free Full Text]
  5. Michel P, Eggert W, Albrecht-Nebe H, Grune T. Increased lipid peroxidation in children with autoimmune diseases. Acta Paediatr (1997) 86:609–12.[Web of Science][Medline]
  6. Serban MG, Tanaseanu S. Lipid peroxidation in autoimmune systemic vasculitides. Effect of corticoid treatment on lipid peroxidation. Antioxidant protection with vitamin E. Rom J Intern Med (1994) 32:137–42.[Medline]
  7. Grune T, Michel P, Sitte N, et al. Increased levels of 4-hydroxynonenal modified proteins in plasma of children with autoimmune diseases. Free Radic Biol Med (1997) 23:357–60.[CrossRef][Web of Science][Medline]
  8. Kurien BT, Scofield RH. Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Sci (2003) 73:1655–66.[CrossRef][Web of Science][Medline]
  9. Kurien BT, Scofield RH. Lipid peroxidation in systemic lupus erythematosus. Indian J Exp Biol (2006) 44:349–56.[Medline]
Accepted 30 June 2008


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This Article
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