Imbalances of CD4(+) T-cell subgroups in Crohn's disease and their relationship with disease activity and prognosis.
OBJECTIVE
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.
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Kang
K
Chao
Shenghong
S
Zhang
Jiayan
J
Yao
Yao
Y
He
Baili
B
Chen
Zhirong
Z
Zeng
Bihui
B
Zhong
Minhu
M
Chen
D044466:Asian People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012306:Risk; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology
D016207:Cytokines
Crohn's disease; Th cell; Treg cell; recurrence; transcription factors