Imbalances of CD4(+) T-cell subgroups in Crohn's disease and their relationship with disease activity and prognosis

Abstract

Background and aim: The CD4(+) T-cell subgroups play central pathophysiological roles in Crohn's disease (CD); however, their clinical relevance requires additional clarification and remains controversial. We investigated their balance in Chinese CD patients and explored their clinical significance.

Methods: Peripheral blood mononuclear cells and serum were collected from 46 Chinese CD patients and 23 healthy donors. Circulating Treg, Th1, Th2, and Th17 cells were flow cytometrically analyzed. Subgroup-restricted transcription factor expression was determined by real-time polymerase chain reaction. Serum concentrations of the main cytokines produced by each subgroup were measured by cytometric bead arrays or enzyme-linked immunosorbent assay.

Results: Lower Treg proportion (6.0 ± 1.2% vs 7.8 ± 1.5%, P = 0.030), FOXP3 mRNA expression (0.58-fold, P = 0.030), and circulating soluble TGFβ-1 (19.1 ± 9.9 vs 32.7 ± 16.8 ng/mL, P = 0.038) were observed in CD patients versus controls. The Th1 and Th17 proportions were higher in CD patients (17.8 ± 6.6% vs 7.8 ± 1.5%, P < 0.001; and 3.7 ± 1.8% vs 1.8 ± 0.7%, P = 0.022, respectively), as were transcription factors T-bet (4.6-fold, P = 0.043) and RORγt (14-fold, P < 0.001) and related cytokines (P < 0.05). Th2 proportion, GATA3 mRNA expression, and serum interleukin-4 concentration in CD patients were similar to controls (P > 0.05). Treg/Th1 and Treg/Th17 ratios were higher in inactive versus active CD patients (0.6 ± 0.4 vs 0.3 ± 0.1, P = 0.022; and 3.7 ± 2.0 vs 1.7 ± 1.4, P = 0.013, respectively). During follow-up, patients with lower Treg/Th1 and Treg/Th17 ratios were at higher recurrence risk.

Conclusions: Imbalances among Treg, Th1, and Th17 subgroups were found in Chinese CD patients. Treg/Th1 and Treg/Th17 ratios are associated with disease activity and are potential prognostic indicators for predicting CD recurrence.

Keywords: Crohn's disease; Th cell; Treg cell; recurrence; transcription factors.