title: Circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive T cells are independently associated with disease damage in systemic lupus erythematosus patients.
abstract: OBJECTIVE
  To determine whether circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive (DP) T cells are independently associated with damage accrual in systemic lupus erythematosus (SLE) patients.
  
  
  METHODS
  This cross-sectional study was conducted between September 2013 and April 2014 in consecutive SLE patients from our Rheumatology Department. CD4+CD28null and CD4+CD8+ DP T-cell frequencies were analyzed by flow-cytometry. The association of damage (SLICC/ACR Damage Index, SDI) and CD4+CD28null and CD4+CD8+ DP T cells was examined by univariable and multivariable Poisson regression models, adjusting for possible confounders. All analyses were performed using SPSS 21.0.
  
  
  RESULTS
  Patients' (n = 133) mean (SD) age at diagnosis was 35.5 (16.8) years, 124 (93.2%) were female; all were mestizo (mixed Caucasian and Amerindian ancestry). Disease duration was 7.4 (6.8) years. The SLE Disease Activity Index was 5.5 (4.2), and the SDI 0.9 (1.2). The percentages of CD4+CD28null and CD4+CD8+ DP T cells were 17.1 (14.4) and 0.4 (1.4), respectively. The percentage of CD4+CD28null and CD4+CD8+ DP T cells were positively associated with a higher SDI in both univariable (rate ratio (RR) 1.02, 95% confidence interval (CI): 1.01-1.03 and 1.17, 95% CI: 1.07-1.27, respectively; p < 0.001 for both) and multivariable analyses RR 1.02, 95% CI: 1.01-1.03, p = 0.001 for CD4+CD28null T cells and 1.28, 95% CI: 1.13-1.44, p < 0.001 for CD4+CD8+ DP T cells). Only the renal domain remained associated with CD4+CD28null in multivariable analyses (RR 1.023 (1.002-1.045); p = 0.034).
  
  
  CONCLUSIONS
  In SLE patients, CD4+CD28null and CD4+CD8+ DP T cells are independently associated with disease damage. Longitudinal studies are warranted to determine the predictive value of these associations.
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru Universidad Científica del Sur, Lima, Peru manuel_ugarte@yahoo.com.
authors.forename: M F
authors.initials: MF
authors.lastname: Ugarte-Gil
authors.affiliation: Molecular Biology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: C
authors.initials: C
authors.lastname: Sánchez-Zúñiga
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: R V
authors.initials: RV
authors.lastname: Gamboa-Cárdenas
authors.affiliation: Molecular Biology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: M
authors.initials: M
authors.lastname: Aliaga-Zamudio
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: F
authors.initials: F
authors.lastname: Zevallos
authors.affiliation: Molecular Biology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: G
authors.initials: G
authors.lastname: Tineo-Pozo
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: J M
authors.initials: JM
authors.lastname: Cucho-Venegas
authors.affiliation: Molecular Biology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: A
authors.initials: A
authors.lastname: Mosqueira-Riveros
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: M
authors.initials: M
authors.lastname: Medina
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru Universidad Nacional Mayor de San Marcos, Lima, Peru.
authors.forename: R A
authors.initials: RA
authors.lastname: Perich-Campos
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
authors.forename: J L
authors.initials: JL
authors.lastname: Alfaro-Lozano
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru Universidad Nacional Mayor de San Marcos, Lima, Peru.
authors.forename: Z
authors.initials: Z
authors.lastname: Rodriguez-Bellido
authors.affiliation: School of Medicine, The University of Alabama at Birmingham, Birmingham, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
authors.affiliation: Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru Universidad Nacional Mayor de San Marcos, Lima, Peru.
authors.forename: C A
authors.initials: CA
authors.lastname: Pastor-Asurza
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018106:CD28 Antigens / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D000068884:Immunosenescence; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens
keywords: Systemic lupus erythematosus; T lymphocytes; disease damage; immunosenescence