Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis

Cuadrado, Emilio; Alonso, Marta; Juan, Montse; Echaniz, Pilar; Arenas, Juan

doi:10.3748/wjg.14.1521

Cited by 40 publications

(31 citation statements)

References 38 publications

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“…Two research groups have reported independently a significant increase in circulating levels of the CD4 + CD25 high+ /FoxP3 phenotype following a course of GMA [43,44].…”

Section: Cd25mentioning

confidence: 99%

The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review

Hanai

Takeda

Eberhardson

et al. 2010

Clinical and Experimental Immunology

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SummaryPatients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid leucocytes such as the CD14 + CD16 + monocytes are major sources of tumour necrosis factor (TNF)-a, and therefore selective granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance efficacy of pharmacological therapy. However, studies in IBD have reported both impressive as well as disappointing efficacy outcomes, indicating that patients' demographic factors might determine responders or nonresponders to GMA. Nonetheless, this non-drug intervention has an excellent safety profile, and therapeutic GMA is expected to expand. In this review, attempts have been made to compile an update on the mode of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than adsorption of excess neutrophils and TNF-producing CD14 + CD16 + monocytes per se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte growth factor and soluble TNF receptors, which are anti-inflammatory. Additionally, a sustained increase in lymphocytes including the regulatory CD4 + CD25 + T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the immune system is potentially very interesting in the context of treating immune-related diseases. Future studies are expected to add intriguing insights to the MoA of GMA.

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“…Two research groups have reported independently a significant increase in circulating levels of the CD4 + CD25 high+ /FoxP3 phenotype following a course of GMA [43,44].…”

Section: Cd25mentioning

confidence: 99%

The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review

Hanai

Takeda

Eberhardson

et al. 2010

Clinical and Experimental Immunology

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“…+ cells may be persistent up to 10 weeks after treatment [21][22][23]. In our study we did not capture the precise duration of the increase in blood Treg.…”

Section: /Foxp3mentioning

confidence: 97%

“…More recently, alterations in T cell subsets has been associated with the beneficial effect of GMA. In particular, in UC a decrease in regulatory CD4 + T cells (Treg) in the intestinal mucosa and an increase in peripheral blood CD4 + Treg has been reported by several authors to correlate with a favourable clinical response [21][22][23]. Treg cells suppress proliferation and cytokine production of activated T cells and are known to play an important role in maintaining peripheral tolerance [24,25].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action

Olsen

Muratov

Cederlund

et al. 2014

Clinical and Experimental Immunology

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SummarySarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis.

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“…The decrea sed LECAM1expression on leucocytes impedes the leukotaxis to the inflamed tissue and CD10negative immature granulocytes appear in the peripheral blood [141,146,147] . Another effect to be mentioned is the removal of the peripheral DCs [148] and the leachate of regulatory Tcells (Tregs) [30,149,150] . Proinflammatory cytokines decrease while anti-inflammatory cytokines increase [151] .…”

Section: Granulocyte Monocyte Apheresismentioning

confidence: 99%

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

Leitner

Vogelsang

2016

WJGPT

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Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroidfree long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8 + T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

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Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis

Abstract: AIM:To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models.

Cited by 40 publications

References 38 publications

The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review

The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review

Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

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