title: Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis.
abstract: Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of < or = 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA.
authors.affiliation: MRC Centre for Immune Regulation, Division of Immunity and Infection, The University of Birmingham, Birmingham, UK. k.raza@bham.ac.uk
authors.forename: Karim
authors.initials: K
authors.lastname: Raza
authors.forename: Dagmar
authors.initials: D
authors.lastname: Scheel-Toellner
authors.forename: Chi-Yeung
authors.initials: CY
authors.lastname: Lee
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.forename: S John
authors.initials: SJ
authors.lastname: Curnow
authors.forename: Francesco
authors.initials: F
authors.lastname: Falciani
authors.forename: Victor
authors.initials: V
authors.lastname: Trevino
authors.forename: Kanta
authors.initials: K
authors.lastname: Kumar
authors.forename: Lakhvir K
authors.initials: LK
authors.lastname: Assi
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Mike
authors.initials: M
authors.lastname: Salmon
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001168:Arthritis / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000503:physiopathology*; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007962:Leukocytes; D008137:Longitudinal Studies; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D013582:Synovial Fluid / Q000166:cytology*; D013997:Time Factors