Caudal type homeobox 2 expression induced by leukocytapheresis might be associated with mucosal healing in ulcerative colitis.

Background And Aim: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells during cytapheresis therapy in a short duration.

Factors associated with treatment outcome, and long-term prognosis of patients with ulcerative colitis undergoing selective depletion of myeloid lineage leucocytes: a prospective multicenter study.

Background: Patients with ulcerative colitis (UC) have elevated/activated myeloid lineage leucocytes and may respond favorably to adsorptive granulocyte/monocyte apheresis (GMA). However, there are patients who respond well to GMA, and patients who do not benefit. Therefore, predictive factors of GMA efficacy need to be defined.

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days.

Crohn's disease complicated by hepatitis B virus successfully treated with the use of adsorptive depletion of myeloid lineage leucocytes to suppress inflammatory cytokine profile.

Background Aims: In patients with inflammatory bowel disease infected with hepatitis B virus (HBV), immunosuppressive therapy required to suppress active inflammatory bowel disease may promote HBV reactivation.

Methods: A 27-year-old corticosteroid-naive woman with Crohn's disease (CD) activity index of 249.8 complicated by HBV infection was offered Entecavir to control HBV reactivation during immunosuppressive therapy for CD.

A novel gas chromatography mass spectrometry-based serum diagnostic and assessment approach to ulcerative colitis.

Background & Aims: To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC.

Methods: Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions.

Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA.

Background: Adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients' demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC.

Methods: In a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated.

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis.

Objective: This study aimed to assess the efficacy and tolerability of leukocytapheresis (LCAP) and to investigate predictive factors for mucosal healing and a sustained clinical response in steroid-free and steroid-refractory patients with ulcerative colitis (UC).

Material And Methods: Thirty-one steroid-free or steroid-refractory patients with active UC were enrolled. Five or ten consecutive sessions of LCAP were performed in each patient.

Adsorptive granulocyte/monocyte apheresis for the maintenance of remission in patients with ulcerative colitis: a prospective randomized, double blind, sham-controlled clinical trial.

Background/aims: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse.

Methods: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy.

Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis.

Background And Aim: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti-inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients.

Current status and future perspectives of leukocytapheresis for inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids.

Optimal apheresis treatment volume for the efficacy and safety of leukocytapheresis with Cellsorba in patients with active ulcerative colitis.

Background: Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume.

Methods: In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA-LCAP) was evaluated in 14 patients with active UC.

Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial.

Background: Infliximab (IFX) is effective for remission induction and maintenance of Crohn's disease (CD). This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence.

Methods: Thirty-one CD patients who had ileocolic resection within the past 4 weeks were randomly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months (n = 15) or without IFX (control, n = 16).

Immunoregulatory effects of adsorptive granulocyte and monocyte apheresis in patients with drug refractory Crohn's disease.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function.

Relevance of the processed blood volume per granulocyte and monocyte apheresis session to its clinical efficacy in patients with ulcerative colitis.

Granulocyte/monocyte adsorption (GMA) has been introduced as an adjunct intervention for active ulcerative colitis (UC) patients. The processed blood volume (PV) per GMA session is an important factor for its efficacy because depletion of elevated/activated myeloid leukocytes is its main action. Hitherto, this aspect of GMA has been largely ignored.

The CD4+CD28null and the regulatory CD4+CD25High T-cell phenotypes in patients with ulcerative colitis during active and quiescent disease, and following colectomy.

The CD4+CD25High T-cell phenotype has an essential immunoregulatory role, while the CD4+CD28null T-cell reflects immune pathology. We investigated the profiles of the CD4+CD25High and the CD4+CD28null T-cell phenotypes in patients with ulcerative colitis (UC) during active and quiescent phases as well as following colectomy. Fifty-nine UC patients, 34 active (UCa) and 25 quiescent (UCq) together with 19 healthy controls (HC) were included.

GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis.

Objective: The roles that amino acids play in immunity and inflammation are well defined, and the relationship between inflammatory bowel disease (IBD) and certain amino acids has recently attracted attention. In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile.

Materials And Methods: Colonic biopsy samples from 22 UC patients were used, as well as serum samples from UC patients (n = 13), Crohn's disease (CD) patients (n = 21), and healthy volunteers (n = 17).

Infliximab therapy impacts the peripheral immune system of immunomodulator and corticosteroid naïve patients with Crohn's disease.

Background/aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX.

Effect and safety of granulocyte-monocyte adsorption apheresis for patients with ulcerative colitis positive for cytomegalovirus in comparison with immunosuppressants.

Background: Cytomegalovirus (CMV) infection exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies (IMT). However, the underlying UC remained active in some UC patients, despite the fact that CMV-DNA in colonic mucosa became negative after antiviral therapy. Therefore, new therapeutic strategies for UC patients concomitant with CMV infection in mucosa are required.

Selective depletion of peripheral granulocyte/monocyte enhances the efficacy of scheduled maintenance infliximab in Crohn's disease.

Background: This is the first report on a case of Crohn's disease (CD), who was successfully maintained with a combination of infliximab (IFX) and selective depletion of granulocytes/monocytes by adsorption (GMA).

Case: A 33-year-old female with CD activity index (CDAI) 294.2 responded to iv IFX (5mg/kg) administered at weeks 0, 2, and 6 in combination with 3000 mg/day oral 5-aminosalicylic acid (5-ASA; CDAI = 118).

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

Objectives: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC.

Cytapheresis in patients with severe ulcerative colitis after failure of intravenous corticosteroid: a long-term retrospective cohort study.

Background/aims: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid.

Multivariate analysis for factors predicting rapid response of leukocytapheresis in patients with steroid-resistant ulcerative colitis: a multicenter prospective open-label study.

Leukocytapheresis (LCAP) has been advocated as a treatment for moderate to severe active ulcerative colitis (UC) in Japan. To clarify the predictive factors for a rapid response to LCAP treatment, we conducted a multicenter prospective open-label study. A total of 105 patients with UC were analyzed.

Hyperthermic stimulation of blood increases the immunological effects of granulocyte and monocyte adsorption in vitro: relevance to extracorporeal immunomodulation.

Extracorporeal granulocyte and monocyte/macrophage adsorption (GMA) using an adacolumn filled with cellulose acetate beads as GMA carriers selectively depletes excess and activated myeloid leucocytes from the circulation and has been used as a non-pharmacologic adjunct therapy in patients with inflammatory bowel disease (IBD). In this study we applied hyperthermic stimulation of blood during exposure to the GMA carriers with the aim of enhancing the release of anti-inflammatory substances from leucocytes. In blood from patients with Crohn's disease (CD) and healthy controls (HC), incubation with the carriers was associated with a striking increase in the release of interleukin-1 receptor antagonist (IL-1ra, a powerful anti-inflammatory cytokine) independent of hyperthermic stimulation, while in the blood from both CD and HC, the release of heat shock protein70 (Hsp70, a cytoprotective protein) was increased by two fold.

Cytapheresis as a Non-Pharmacological Therapy for Inflammatory Bowel Disease.

SUMMARY: Although inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic recurrent disease with unknown etiology. Recent immunological studies suggest close relation to autoimmune status featured by antibodies against colonic epithelial cells. For patients with IBD, 5-aminosalycilates are often used in case of mild disease, and corticosteroids are standard therapy for moderate-to-severe disease.

Therapeutic leukocytapheresis for inflammatory bowel disease.

The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD, GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14(+)CD16(+) monocytes and was followed by an increase in CD4(+) T lymphocytes including the regulatory CD4(+)CD25(high+)Foxp3 phenotype.