An imbalance in the T-helper phenotypes displayed by senescent CD4+CD28null T cells is associated with erosive arthritis (rhupus syndrome) in systemic lupus erythematosus

Abstract

Objective: The objective was to assess the proportion of Th1, Th2 and Th17 phenotypes in senescent CD4⁺CD28^null cells from patients with systemic lupus erythematosus (SLE) and its association with the pattern of joint involvement.

Methods: This cross-sectional study was performed in SLE patients with erosive arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4⁺CD28^null cells as well as the proportion of these cells expressing T-bet, GATA3 or RORγt were analyzed by color-flow cytometry. Serum osteopontin levels were measured by ELISA.

Results: Eighteen SLE patients (nine with rhupus and nine with nonerosive arthritis) were studied. The percentage of CD4⁺CD28^null/CD4⁺ cells (17.7%, 10.3-25.0% versus 9.4%, 8.1-22.4%; P = 0.386) as well as the osteopontin levels (5800, 5,134-5995 pg/ml versus 5578, 5171-5717 pg/ml; P > 0.05) were similar in both groups. A higher percentage of CD4⁺CD28^nullT-bet⁺ cells (42.8%, 33.5-53.4% versus 30.0%, 23.3-34.2%) but a lower percentage of CD4⁺CD28^nullGATA3⁺ cells (3.1%, 1.7-5.6% versus 6.2%, 2.6-18.4%) was observed in patients with rhupus than in their counterparts ( P = 0.016). The frequency of CD4⁺CD28^nullRORγt⁺ cells was similar between groups.

Conclusions: In patients with rhupus, senescent CD4⁺CD28^null cells are preferentially polarized to a Th1 phenotype, whereas this is partial towards Th2 in lupus patients with a nonerosive arthritis pattern.

Keywords: CD4+CD28null cells; Systemic lupus erythematosus; arthritis; osteopontin; rhupus; senescence.