Apoptosis Resistance of Mucosal Lymphocytes and IL-10 Deficiency in Patients with Steroid-refractory Crohn's Disease

被引:24
作者
Santaolalla, Rebeca [1 ]
Mane, Josep [2 ,3 ]
Pedrosa, Elisabet [2 ,3 ]
Loren, Violeta [2 ,3 ]
Fernandez-Banares, Fernando [1 ]
Mallolas, Josefa [1 ]
Carrasco, Anna [1 ]
Salas, Antonio [4 ]
Rosinach, Merce [1 ]
Forne, Montserrat [1 ]
Espinos, Jorge C. [1 ]
Loras, Carme [1 ]
Donovan, Michael [5 ]
Puig, Pere [5 ]
Manosa, Miriam [3 ,6 ]
Gassull, Miquel A.
Viver, Josep M. [1 ]
Esteve, Maria [1 ]
机构
[1] Univ Barcelona, Dept Gastroenterol, Hosp Univ Mutua Terrassa, Res Fdn Mutua Terrassa, Barcelona 08221, Catalonia, Spain
[2] Germans Trias & Pujol Fdn, Hlth Sci Res Inst, Gastroenterol & Nutr Res Unit, Badalona, Catalonia, Spain
[3] CIBERehd, Barcelona, Catalonia, Spain
[4] Univ Barcelona, Dept Pathol, Hosp Univ Mutua Terrassa, Res Fdn Mutua Terrassa, Barcelona 08221, Catalonia, Spain
[5] Althia, Adv Labs Translat Hlth, Barcelona, Catalonia, Spain
[6] Hosp Badalona Germans Trias & Pujol, Dept Gastroenterol, Badalona, Catalonia, Spain
关键词
lymphocyte apoptosis resistance; Crohn's disease; IL-10; steroid resistance; INFLAMMATORY-BOWEL-DISEASE; CASPASE-DEPENDENT PATHWAY; T-CELLS; TNF-ALPHA; ULCERATIVE-COLITIS; B-CELLS; INFLIXIMAB; DEATH; ETANERCEPT; RECURRENCE;
D O I
10.1002/ibd.21507
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Background: Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. Methods: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7-10 clays after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by How cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). Results: Apoptosis resistance of T and B lymphocytes was observed only in steroid-refractory and -dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)-10 was markedly increased at baseline in steroid-responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). Conclusions: Apoptosis resistance of mucosal T and B cells in steroid-refractory and -dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL-10 at an early stage of active steroid-sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid-dependent and -refractory CD patients share similar molecular and cellular pathophysiological mechanisms.
引用
收藏
页码:1490 / 1500
页数:11
相关论文
共 35 条
[1]
BEST WR, 1979, GASTROENTEROLOGY, V77, P843
[2]
A novel regulatory B-cell population in sheep Peyer's patches spontaneously secretes IL-10 and downregulates TLR9-induced IFNα responses [J].
Booth, J. S. ;
Griebel, P. J. ;
Babiuk, L. A. ;
Mutwiri, G. K. .
MUCOSAL IMMUNOLOGY, 2009, 2 (03) :265-275
[3]
Improved prediction of prostate cancer recurrence through systems pathology [J].
Cordon-Cardo, Carlos ;
Kotsianti, Angeliki ;
Verbel, David A. ;
Teverovskiy, Mikhail ;
Capodieci, Paola ;
Hamann, Stefan ;
Jeffers, Yusuf ;
Clayton, Mark ;
Elkhettabi, Faysal ;
Khan, Faisal M. ;
Sapir, Marina ;
Bayer-Zubek, Valentina ;
Vengrenyuk, Yevgen ;
Fogarsi, Stephen ;
Saidi, Olivier ;
Reuter, Victor E. ;
Scher, Howard I. ;
Kattan, Michael W. ;
Bianco, Fernando J., Jr. ;
Wheeler, Thomas M. ;
Ayala, Gustavo E. ;
Scardino, Peter T. ;
Donovan, Michael J. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (07) :1876-1883
[4]
Defective IL-10 production in severe phenotypes of Crohn's disease [J].
Correa, Ismael ;
Veny, Marisol ;
Esteller, Miriam ;
Pique, Josep M. ;
Yaguee, Jordi ;
Panes, Julian ;
Salas, Azucena .
JOURNAL OF LEUKOCYTE BIOLOGY, 2009, 85 (05) :896-903
[5]
Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD [J].
Daperno, M ;
D'Haens, G ;
Van Assche, G ;
Baert, F ;
Bulois, P ;
Maunoury, V ;
Sostegni, R ;
Rocca, R ;
Pera, A ;
Gevers, A ;
Mary, JY ;
Colombel, JF ;
Rutgeerts, P .
GASTROINTESTINAL ENDOSCOPY, 2004, 60 (04) :505-512
[6]
Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease [J].
Di Sabatino, A ;
Ciccocioppo, R ;
Cinque, B ;
Millimaggi, D ;
Morera, R ;
Ricevuti, L ;
Cifone, MG ;
Corazza, GR .
GUT, 2004, 53 (01) :70-77
[7]
Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn's disease [J].
Doering, J ;
Begue, B ;
Lentze, MJ ;
Rieux-Laucat, F ;
Goulet, O ;
Schmitz, J ;
Cerf-Bensussan, N ;
Ruemmele, FM .
GUT, 2004, 53 (11) :1632-1638
[8]
Rapid and simple comparison of messenger RNA levels using real-time PCR [J].
Dussault, AA ;
Pouliot, M .
BIOLOGICAL PROCEDURES ONLINE, 2006, 8 (1) :1-10
[9]
RELATIONSHIP BETWEEN DISEASE-ACTIVITY INDEXES AND COLONOSCOPIC FINDINGS IN PATIENTS WITH COLONIC INFLAMMATORY BOWEL-DISEASE [J].
GOMES, P ;
DUBOULAY, C ;
SMITH, CL ;
HOLDSTOCK, G .
GUT, 1986, 27 (01) :92-95
[10]
Immunopathogenesis of IBD: Insufficient suppressor function in the gut? [J].
Huibregtse, I. L. ;
van Lent, A. U. ;
van Deventer, S. J. H. .
GUT, 2007, 56 (04) :584-592