title: Autoantibodies to the translational suppressors T cell intracytoplasmic antigen 1 and T cell intracytoplasmic antigen 1-related protein in patients with rheumatic diseases: increased prevalence in systemic lupus erythematosus and systemic sclerosis and correlation with clinical features.
abstract: OBJECTIVE
  T cell intracytoplasmic antigen 1 (TIA-1) and TIA-1-related protein (TIAR) are involved in posttranscriptional regulation of the expression of tumor necrosis factor alpha (TNFalpha) and other proteins. Given the pivotal role of TNFalpha in chronic inflammatory diseases, this study was undertaken to analyze sera from patients with systemic autoimmune diseases for the presence of autoantibodies to TIA proteins and to investigate the expression of these proteins in inflamed tissue.
  
  
  METHODS
  The presence of autoantibodies to TIA proteins in sera from 385 patients with rheumatic diseases and healthy controls was determined by immunoblotting using recombinant antigens. Expression of TIA proteins in skin and kidney tissue was analyzed by immunohistochemistry. Serum levels of TNFalpha were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Autoantibodies to TIA-1 and/or TIAR were detected in 61% of patients with systemic lupus erythematosus (SLE), 42% of patients with systemic sclerosis (SSc), 15-31% of patients with other rheumatic diseases, and 6% of healthy controls. Compared with patients negative for anti-TIA antibody, anti-TIA antibody-positive SLE patients had higher disease activity (P = 0.01), elevated antibodies to double-stranded DNA (P = 0.0003), and increased serum TNFalpha levels (P = 0.018). In SLE patients, anti-TIAR antibodies were associated with lupus nephritis (P = 0.02), while in patients with SSc, anti-TIA-1 was associated with lung involvement (P = 0.02). Immunohistochemical analysis of skin and kidney tissue revealed aberrant expression of TIA proteins in skin lesions from SLE and SSc patients, as well as in glomerular cells from SLE patients.
  
  
  CONCLUSIONS
  Aberrant expression of TIA proteins in inflammatory tissue may lead to systemic autoantibody responses, particularly in SLE and SSc. Increased occurrence of anti-TIA autoantibodies in patients with severe organ involvement may point to a possible pathogenetic role.
authors.affiliation: Technical University Dresden, Dresden, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Jimenez-Boj
authors.forename: Nancy
authors.initials: N
authors.lastname: Kedersha
authors.forename: Makiyeh
authors.initials: M
authors.lastname: Tohidast-Akrad
authors.forename: Franz M
authors.initials: FM
authors.lastname: Karlhofer
authors.forename: Georg
authors.initials: G
authors.lastname: Stummvoll
authors.forename: Christof
authors.initials: C
authors.lastname: Zimmermann
authors.forename: Walter
authors.initials: W
authors.lastname: Ulrich
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hoefler
authors.forename: Martin
authors.initials: M
authors.lastname: Aringer
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D039102:Poly(A)-Binding Proteins / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D001323:Autoantibodies; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C076751:TIAL1 protein, human