title: Distinct autoantibody profiles in systemic lupus erythematosus patients are selectively associated with TLR7 and TLR9 upregulation.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) patients have a wide array of autoantibodies against nuclear antigens. The two predominant classes of these autoantibodies are directed either against dsDNA or RNA-associated antigens (extractable nuclear antigens; ENA). Nucleic-acid sensing Toll-like receptors (TLRs) that recognize dsDNA and RNA, have been well implicated in some murine models of SLE. We took up this study to identify if unique TLR expression patterns are associated with distinct autoantibody profiles in SLE.
  
  
  METHODS
  We segregated the patients into three subsets distinguished on the basis of autoantibody response either against dsDNA or ENA or both. We determined the mRNA expression of TLR3, 7, 8, and 9 by real-time reverse-transcription PCR in peripheral blood leucocytes (PBLs) of the SLE patients of all three subsets. TLR7 and 9 protein expression was determined by western blotting in PBLs and by flow cytometry on B-cells and monocytes. The serum interferon-alpha (IFN-α) and anti-dsDNA/-ENA autoantibodies were detected using enzyme-linked immunosorbant assay.
  
  
  RESULTS
  We report differential and unique TLR expression patterns associated with different autoantibody profiles. The presence of anti-ENA and anti-dsDNA autoantibodies in SLE patients was associated with elevated levels of TLR7 and TLR9 respectively. The TLR9 mRNA expression was further augmented in SLE patients with Glomerulonephritis. Interestingly, anti-dsDNA(+) ENA(+) patients displayed higher serum IFN-α and interferon regulatory factor 7 mRNA expression than patients with either anti-dsDNA or anti-ENA autoantibodies alone.
  
  
  CONCLUSIONS
  Characteristic TLRs expression profile associated with distinct autoantibody repertoire is suggestive of differential immuno-regulatory pathways operative in different subsets of SLE patients.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Sudhir Kumar
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Vikas Vikram
authors.initials: VV
authors.lastname: Singh
authors.forename: Richa
authors.initials: R
authors.lastname: Rai
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.forename: Geeta
authors.initials: G
authors.lastname: Rai
mesh_terms: D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D034961:Antigens, Nuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D001323:Autoantibodies; D016898:Interferon-alpha; D012333:RNA, Messenger; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
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