title: Behçet's disease heterogeneity: cytokine production and oxidative burst of phagocytes are altered in patients with severe manifestations.
abstract: OBJECTIVE
  To test the hypothesis that classical phagocytic functions are constitutively stimulated in patients with Behçet's disease (BD).
  
  
  METHODS
  Four study groups were analysed: active BD (aBD; n=30), inactive BD (iBD; n=31); septic patients (SP; n=25); healthy controls (HC; n=30). Microbicide activity against Streptococcus pneumoniae, Streptococcus sanguinis and Candida albicans was determined by means of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and absorbance read by ELISA. Flow cytometry analysis evaluated phagocytosis (zymosan particles and microrganisms) and oxidative burst by dihidrorhodamine oxidation before and after stimulation with phorbol myristate acetate (PMA). The supernatant of PBMC cultures under TLR or microbial stimuli and of neutrophil cultures under PMA, LPS or microbial stimuli were used for determination of cytokine production by ELISA.
  
  
  RESULTS
  We found no significant differences between the BD patient groups and control groups with regard to oxidative burst, phagocytic activity, microbicide activity or cytokine production. However, the cells from patients with severe BD (based on clinical manifestation) exhibit significantly higher oxidative burst activity, both before and after PMA stimulation, compared to cells from patients with mild BD. Furthermore, we found significant correlations between the BD patients' scores on the simplified Behçet's Disease Current Activity Form adapted for Portuguese (BR-BDCAFs) and Streptococcus sanguinis-stimulated production of IL23 by PBMC and IL8 by neutrophils, and between BR-BDCAFs score and constitutive production of TNF-α, IFNγ, IL6 and IL23 by PBMC.
  
  
  CONCLUSIONS
  Patients with severe active BD do exhibit phagocytic dysfunction and some evidence of constitutive activation regarding oxidative burst and cytokine production.
authors.affiliation: Division of Rheumatology, Federal University of São Paulo, São Paulo; and Fleury Group, Research and Development, São Paulo, Brazil.
authors.forename: Sandro F
authors.initials: SF
authors.lastname: Perazzio
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo Vitor
authors.initials: PV
authors.lastname: Soeiro-Pereira
authors.affiliation: Division of Rheumatology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Alexandre Wagner S
authors.initials: AW
authors.lastname: de Souza
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Antônio
authors.initials: A
authors.lastname: Condino-Neto
authors.affiliation: Division of Rheumatology, Federal University of São Paulo, São Paulo; and Fleury Group, Research and Development, São Paulo, Brazil. luis.andrade@unifesp.br.
authors.forename: Luis Eduardo C
authors.initials: LE
authors.lastname: Andrade
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D016897:Respiratory Burst / Q000187:drug effects; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000276:immunology; D013298:Streptococcus sanguis / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D013755:Tetradecanoylphorbol Acetate