title: Interleukin 10 and tumor necrosis factor-alpha genotypes in rheumatoid arthritis--association with clinical response to glucocorticoids.
abstract: OBJECTIVE
  There are dysregulated levels of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis (RA), and their role in the disease is controversial. We analyzed the association of functional polymorphisms of IL-10 and TNF-alpha with susceptibility and disease characteristics at the time of diagnosis, and we also evaluated their possible use as predictors of clinical response to treatments.
  
  
  METHODS
  Patients with recent-onset RA (n = 162) and healthy controls (n = 373) were genotyped for -1082 IL-10 and -308 TNF-alpha polymorphisms and data were related to clinical and immunological measurements of patients at the time of diagnosis. Response to treatment after 6 months was determined in 125 patients by the absolute change in Disease Activity Score (DAS28) and the American College of Rheumatology criteria for improvement.
  
  
  RESULTS
  We found a reduced frequency of the low IL-10 producer genotype (-1082AA) in patients with RA compared to controls (26.5% vs 38.9%; p = 0.006), while it is a risk factor for anticyclic citrullinated peptide antibodies (anti-CCP) positivity (p = 0.028). Evaluation of clinical response to treatments indicated that carriage of the high IL-10 genotype was associated with a favorable outcome (p = 0.009), specifically to prednisone therapy (p = 0.0003). No significant effects were observed with TNF-alpha polymorphism alone; however, in combination with the IL-10 genotype, it increased the strength of these associations.
  
  
  CONCLUSIONS
  Results show an association between the low IL-10 producer genotype and protection from RA; nevertheless, when other specific genetic and/or environmental factors trigger onset of RA, this genotype may predispose to development of anti-CCP+ RA disease with reduced response to prednisone treatment.
authors.affiliation: Department of Functional Biology, Immunology Area, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: Banesa
authors.initials: B
authors.lastname: de Paz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alperi-López
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ballina-García
authors.forename: Catuxa
authors.initials: C
authors.lastname: Prado
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mozo
authors.forename: Carmen
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000906:Antibodies; D005938:Glucocorticoids; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D016753:Interleukin-10