Steady-State Cell Apoptosis and Immune Tolerance - Induction of Tolerance Using Apoptotic Cells in Type 1 Diabetes and Other Immune-Mediated Disorders

Xia, Chang-Qing; Campbell, Kim; Benjamin, Keselowsky; Clare‐Salzler, Michael

doi:10.5772/22113

Cited by 2 publications

(2 citation statements)

References 135 publications

(104 reference statements)

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“…And yet, data on peripheral lymphocytes and their sensitivity to apoptosis seems to be scanty and contradictory. On one hand, induction of their apoptosis via ECP is viewed as a therapeutic option [ 15 ], implying peripheral lymphocytes in IBD to be resistant to apoptosis as well. On the other, however, percentage of apoptotic cells is claimed to be increased in patients with IBD flare and hold responsible for the systemic nature of disease and its extraintestinal manifestations [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Peripheral Lymphocytes of Patients with Inflammatory Bowel Disease Have Altered Concentrations of Key Apoptosis Players: Preliminary Results

Neubauer

Woźniak−Stolarska

Krzystek−Korpacka

2018

BioMed Research International

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Notwithstanding uncertain pathogenesis of inflammatory bowel disease (IBD), deregulation of adaptive immunity is paramount for the development of inflammation. Essential role in the resolution of inflammation is played by apoptosis, deregulated in lymphocytes isolated from inflamed intestine. Despite IBD being a systemic disease, little is known about apoptosis of peripheral lymphocytes. The concentrations of Bcl-2, cytochrome c, p53, and caspase-9 were determined (ELISA) in lymphocyte-enriched fractions of peripheral blood mononuclear cells (LE-PBMCs) from 64 individuals (42 with IBD) and related to IBD phenotype and activity, treatment, and inflammatory and hematological indices. The diagnostic potential of evaluated markers was determined as well. All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC). Caspase 9 was significantly lower in active IBD and Bcl-2 in active UC whereas cytochrome c was higher in active CD. Treatment with corticosteroids affected the concentrations of cytochrome c and p53. Both positively correlated with hsCRP and the concentrations of all markers were interrelated. As IBD markers, Bcl-2 and caspase-9 displayed good accuracy and, as a panel of markers with cytochrome c, their accuracy was excellent (92%). As CD markers Bcl-2, cytochrome c, and p53 displayed fair accuracy but combined determination of Bcl-2 and cytochrome c improved the accuracy to 85%. Taken together, our results imply diminished intrinsic apoptotic capacity of LE-PBMCs in IBD but an upregulation of proapoptotic features parallel to increasing severity of inflammation. Observed abnormalities in intrinsic pathway of apoptosis are more pronounced in CD. Upon positive validation on a larger set of patients, combined quantification of Bcl-2 and cytochrome c might be considered as an adjunct in differential diagnosis of UC and CD of colon and rectum.

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Section: Discussionmentioning

confidence: 99%

“…It is also an aim of prospective immunotherapies, such as extracorporeal photopheresis (ECP) in which patients' lymphocytes are exposed to a photoactivatable drug with cytotoxic effect. ECP has recently been successfully tested in CD patients with the disease refractory to immunosuppression and/or anti-TNF therapies (reviewed in [ 15 ]).…”

Section: Introductionmentioning

confidence: 99%