Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.

Abstract

BackgroundT‐cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA‐4 play major roles in regulating the stimulatory and inhibitory co‐signals in T cells.ObjectiveTo analyze the association between soluble and surface expression of CD28 and CTLA‐4 with the clinical parameters of RA patients.MethodsA total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age‐ and sex‐matched control subjects (CS) were included. Surface expression of CD28 and CTLA‐4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA‐4 (sCTLA‐4), and anti‐CCP antibodies were measured by ELISA.ResultsA significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA‐4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti‐CCP levels (rho = −0.12; P = .032). The soluble and surface expressions of CTLA‐4 were not associated with RA clinical parameters.ConclusionsIn RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti‐CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated RA patients.