Granulocytes and monocytes apheresis induces upregulation of TGFβ₁ in patients with active ulcerative colitis: A possible involvement of soluble HLA‐I

Abstract

Granulocyte and monocyte apheresis has been used in different immune-mediated disorders, mainly inflammatory bowel diseases. The removal of activated leukocytes and several additional immunomodulatory mechanisms have been so far suggested to explain the anti-inflammatory effects of the treatment. Recent data indicate that, during centrifugation based apheresis, sHLA-I adsorbed to plastic circuits is able to induce TGFβ production in activated leukocytes. On these bases, the present study was aimed at analyzing if this model could be applied to a noncentrifugation based apheresis, such as granulocyte and monocyte apheresis. Ten patients with ulcerative colitis were enrolled. Every patient received 5 weekly apheresis treatments. Cellulose acetate beads removed from the column post-GMA were stained by fluorescent anticlass I mAb and examined by fluorescent microscope. Moreover, sFasL plasma concentration, TGFβ plasma levels, and the percentage of TGFβ positive neutrophils were evaluated before and immediately after each single apheresis. Immunofluorescent images revealed a homogeneous layer of a sHLA-I adsorbed to the surface of the beads recovered following the procedure. sFasL plasma concentration progressively increased both following the procedures and during inter-procedure periods. Consistently, also TGFβ plasma levels and the percentage of TGFβ positive neutrophils increased during the procedures with a meaningful relationship with sFasL plasma levels. Taken together, these findings suggest that the immunosuppressive effects attributed to granulocyte and monocyte apheresis might depend, at least in part, on the sensitivity of activated leucocytes to the bioactivity of sHLA-I molecules. J. Clin. Apheresis 32:49-55, 2017. © 2016 Wiley Periodicals, Inc.

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

“…In addition, the serum TGF-b1 concentration increased in response to conventional IBD treatments, suggesting that TGF-b is required for suppression of intestinal inflammation in active UC patients [19,25]. Contini et al reported that serum TGF-b1 and TGF-b-expressing-neutrophils increased during granulocyte and monocyte apheresis therapy in patients with active UC [26].…”

Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis

“…GMA is currently available for the treatment of active UC that has had loss of response to standard pharmacotherapies, including biologics. Activated granulocytes and monocytes (GMs) adsorption to cellulose acetate beads induces downregulation of inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and TNF-α and release of anti-inflammatory cytokine [7][8][9][10]. Therefore, levels of these cytokines in the intestinal tissue were significantly lowered in inflammatory bowel disease (IBD) patients who had achieved clinical or endoscopic remission, compared to patients who clinically remained unchanged after GMA therapy [11].…”