title: TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients.
abstract: BACKGROUND
  Expansion of CD4(+)CD28(null), a common feature of immunosenescence, which has been reported in rheumatoid arthritis (RA) patients, may also be associated with a CD4(+) imbalance. Although the increase of CD4(+)CD28(null) cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine.
  
  
  METHODS
  Participants were genotyped for TNFA rs1800629 (-308 G>A) and frequency of the CD4(+)CD28(null), regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls.
  
  
  RESULTS
  The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele. Analysis of regulatory T cells and IFNγ-CD4(+) expression suggested that defective suppression and/or Th1-shift could underlie the expansion of this population in these patients. Finally, although treatment with TNFα-blockers reduced CD4(+)CD28(null) cells in most patients, only those carriers of the common GG genotype reached values within the range of HC and showed a disease activity improvement correlated to this decrease.
  
  
  CONCLUSIONS
  Our results provide evidence for a genetic basis of the premature immunosenescence of RA patients and highlight its potential role in clinical outcome after TNFα blockade.
authors.affiliation: Area of Immunology, Departament of Functional Biology, University of Oviedo, Asturias, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alperi-López
authors.affiliation: Area of Immunology, Departament of Functional Biology, University of Oviedo, Asturias, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Alonso-Castro
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ballina-García
authors.affiliation: Area of Immunology, Departament of Functional Biology, University of Oviedo, Asturias, Spain. Electronic address: anasua@uniovi.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D018106:CD28 Antigens; D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha
keywords: CD4(+)CD28(null) cells; Immunosenescence; Rheumatoid arthritis; TNFA polymorphisms