Recent advances and opportunities in research on Lupus: Environmental influences and mechanisms of disease

Glinda S. Cooper, Kathleen M. Gilbert, Eric L Greidinger, Judith A. James, Jean C. Pfau, Leslie Reinlib, Bruce C. Richardson, Noel R. Rose

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Objectives: In this review we summarize research on mechanisms through which environmental agents may affect the pathogenesis of lupus, discuss three exposures that have been the focus of research in this area, and propose recommendations for new research initiatives. Data sources and synthesis: We examined studies pertaining to key mechanistic events and specific exposures. Apoptosis leading to increased production or decreased clearance of immunogenic intracellular self-antigens and defective apoptosis of autoreactive immune cells both have been implicated in the loss of self-tolerance. The adjuvant or bystander effect is also needed to produce a sustained autoimmune response. Activation of toll-like receptors is one mechanism through which these effects may occur. Abnormal DNA methylation may also contribute to the pathogenesis of lupus. Each of the specific exposures we examined - Epstein-Barr virus, silica, and trichloroethylene - has been shown, in humans or in mice, to act upon one or more of these pathogenic steps. Specific recommendations for the continued advancement of our understanding of environmental influences on lupus and other autoimmune diseases include the development and use of mouse models with varying degrees of penetrance and manifestations of disease, identification of molecular or physiologic targets of specific exposures, development and use of improved exposure assessment methodologies, and multisite collaborations designed to examine understudied environmental exposures in humans. Conclusions: The advances made in the past decade concerning our understanding of mechanisms involved in the development of lupus and the influence of environmental agents on this process provide a strong foundation for further developments in this field.

Original languageEnglish
Pages (from-to)695-702
Number of pages8
JournalEnvironmental Health Perspectives
Volume116
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

Research
Apoptosis
Bystander Effect
Self Tolerance
Trichloroethylene
Penetrance
Toll-Like Receptors
Information Storage and Retrieval
Environmental Exposure
apoptosis
Autoantigens
DNA Methylation
Autoimmunity
Human Herpesvirus 4
Viruses
Silicon Dioxide
Autoimmune Diseases
Chemical activation
methylation
trichloroethylene

Keywords

  • Adjuvant effect
  • Apoptosis
  • Autoimmune diseases
  • Bystander effect
  • Demethylation
  • Epigenetics
  • Epstein-Barr virus
  • Silica
  • Systemic lupus erythematosus
  • Trichloroethylene

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Recent advances and opportunities in research on Lupus : Environmental influences and mechanisms of disease. / Cooper, Glinda S.; Gilbert, Kathleen M.; Greidinger, Eric L; James, Judith A.; Pfau, Jean C.; Reinlib, Leslie; Richardson, Bruce C.; Rose, Noel R.

In: Environmental Health Perspectives, Vol. 116, No. 6, 01.06.2008, p. 695-702.

Research output: Contribution to journalArticle

Cooper, GS, Gilbert, KM, Greidinger, EL, James, JA, Pfau, JC, Reinlib, L, Richardson, BC & Rose, NR 2008, 'Recent advances and opportunities in research on Lupus: Environmental influences and mechanisms of disease', Environmental Health Perspectives, vol. 116, no. 6, pp. 695-702. https://doi.org/10.1289/ehp.11092
Cooper, Glinda S. ; Gilbert, Kathleen M. ; Greidinger, Eric L ; James, Judith A. ; Pfau, Jean C. ; Reinlib, Leslie ; Richardson, Bruce C. ; Rose, Noel R. / Recent advances and opportunities in research on Lupus : Environmental influences and mechanisms of disease. In: Environmental Health Perspectives. 2008 ; Vol. 116, No. 6. pp. 695-702.
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