A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.

2.50
Hdl Handle:
http://hdl.handle.net/2436/117096
Title:
A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.
Authors:
Freimanis, Graham L.; Hooley, Paul; Ejtehadi, H Dava; Ali, H. A.; Veitch, A.; Rylance, P.; Alawi, A.; Axford, J.; Nevill, Alan M.; Murray, Paul G.; Nelson, Paul N.
Abstract:
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.
Citation:
Clinical and experimental immunology, 160 (3):340-7
Publisher:
Wiley-Blackwell
Journal:
Clinical and experimental immunology
Issue Date:
2010
URI:
http://hdl.handle.net/2436/117096
DOI:
10.1111/j.1365-2249.2010.04110.x
PubMed ID:
20345981
Type:
Article
Language:
en
ISSN:
1365-2249
Appears in Collections:
Applied Microbiology Research Group; Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorFreimanis, Graham L.en
dc.contributor.authorHooley, Paulen
dc.contributor.authorEjtehadi, H Davaen
dc.contributor.authorAli, H. A.en
dc.contributor.authorVeitch, A.en
dc.contributor.authorRylance, P.en
dc.contributor.authorAlawi, A.en
dc.contributor.authorAxford, J.en
dc.contributor.authorNevill, Alan M.en
dc.contributor.authorMurray, Paul G.en
dc.contributor.authorNelson, Paul N.en
dc.date.accessioned2010-12-03T13:00:36Z-
dc.date.available2010-12-03T13:00:36Z-
dc.date.issued2010-
dc.identifier.citationClinical and experimental immunology, 160 (3):340-7en
dc.identifier.issn1365-2249-
dc.identifier.pmid20345981-
dc.identifier.doi10.1111/j.1365-2249.2010.04110.x-
dc.identifier.urihttp://hdl.handle.net/2436/117096-
dc.description.abstractHuman endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshArthritis, Rheumatoiden
dc.subject.meshAutoantigensen
dc.subject.meshEndogenous Retrovirusesen
dc.subject.meshEpitopesen
dc.subject.meshFemaleen
dc.subject.meshGene Expression Regulation, Viralen
dc.subject.meshGene Products, gagen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMolecular Mimicryen
dc.subject.meshPeptidesen
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshRNA, Messengeren
dc.subject.meshRNA, Viralen
dc.subject.meshSynovial Membraneen
dc.subject.meshTranscription, Geneticen
dc.titleA role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.en
dc.typeArticleen
dc.identifier.journalClinical and experimental immunologyen

Related articles on PubMed

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.