GMA in Inflammatory
Bowel Disease (IBD)


The rationale for the use of granulocyte-monocyte
apheresis (GMA) in the treatment of IBD

In any immune-mediated disease there is an initial and essential step for inflammation to occur in any of the affected organs: the recruitment of inflammatory cells from the bloodstream into inflamed tissues.

Once there, these inflammatory cells secrete a variety of substances whose function will be, on the one hand, to recruit more inflammatory cells and, on the other, to cause tissue damage typical of each disease. 

Initially, the treatment used in immune-mediated diseases was based on the administration of non-selective corticosteroids and immunosuppressants, whose mechanism of action affected multiple levels and had a high rate of side effects.

In the last two decades, the treatment of these diseases has evolved towards the use of much more selective therapies and, therefore, more predictable therapeutic as well as collateral effects.

In the case of Immflamatory Bowel Disease (IBD), although other cells such as lymphocytes and monocytes have a certain role, the main inflammatory cells involved in the pathogenic mechanism are neutrophils, white blood cells, also called granulocytes.

Neutrophils are actively recruited from the bloodstream into the mucous layer of the intestine, causing the typical lesions of this disease through their degranulation and the release of various proteinases and chemokines.

In fact, the neutrophil’s significance in this disease is such that several studies have shown a strong correlation between the presence of neutrophils in the gastrointestinal wall of patients with IBD and the risk of clinical relapse (disease “flare-up”) or colon cancer.

Another fact that demonstrates the relevance of neutrophil presence in the intestinal linen of patients with IBD is the utility of faecal calprotectin measurement regarding the prediction of relapses or the diagnosis of disease activity even in the absence of symptoms. Faecal calprotectin is the main protein in the cytoplasm of neutrophils and is detectable in stools, as long as the intestinal tract mucosa is infiltrated by neutrophils. The physicochemical characteristics of this protein and its resistance to degradation by bacteria of the colon have allowed its use in clinical practice, making it the most used and reliable parameter for the management and evaluation of patients with IBD, specially with UC. 

Granulocyte-monocyte apheresis (GMA) acts specifically by preventing the migration of granulocytes (neutrophils) and activated monocytes to the gastrointestinal wall (1). Adacolumn® cellulose acetate beads have been shown to absorb circulating immunocomplexes and IgGs in addition to activating certain complement fragments (specifically C3a and C5a); this allows the system to selectively absorb granulocytes (via Fc receptors) and monocytes (via complement receptors). In addition to this “mechanical effect”, it has been found that cellulose beads can activate neutrophil apoptosis (which is reduced in UC). Various studies have shown that cellulose beads and the presence of neutrophil apoptotic bodies also increase the synthesis of anti- inflammatory cytokines (IL-10, IL-1ra, HGF) and achieve the reduction of pro-inflammatory cytokines  (TNF-α, IL-6, IL-8, IL-1β) (2). Due to the mobilization of white blood cells from the bone marrow, this “withdrawal” of activated neutrophils and monocytes from the bloodstream does not follow a reduction in the total number of these cells in the blood, because they are replaced by immature or inactive cells. This would explain why the application of GMA is not accompanied by an increased risk of infections or tumours observed with most immunosuppressive drugs (1). 1.- Hanai H1, Takeda YEberhardson MGruber RSaniabadi ARWinqvist OLofberg R. The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review, Clin Exp Immunol. 2011 Jan;163(1):50-8.DOI: 10.1111/j.1365-2249.2010.04279.x. 2.- Saniabadi AR1, Hanai HTakeuchi KUmemura KNakashima MAdachi TShima CBjarnason ILofberg R. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003 Feb;7(1):48-59. DOI: 10.1046/j.1526-0968.2003.00012.x

Mechanism of action of GMA (1)
General overview

In summary, GMA achieves (1):
  • a reduction of activated neutrophils and monocytes in the bloodstream.
  • an increase of anti-inflammatory cytokines.
  • a decrease of pro-inflammatory cytokines.
This is done without inducing immunosuppression, therefore GMA offers a therapeutic effect without the debilitating side effects usually associated with immunosuppressive drugs.

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