Monocyte Adsorption Apheresis Research Articles

P614 The utility as a biomarker of faecal calprotectin for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis treatment in patients with ulcerative colitis

P614 The utility as a biomarker of faecal calprotectin for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis treatment in patients with ulcerative colitis

Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis.

Pustulotic arthro-osteitis, occasionally complicated with palmoplantar pustulosis, affects patients' activities of daily living. Granulocyte and monocyte adsorption apheresis selectively removes activated granulocytes and monocytes by means of extracorporeal circulation. Although the efficacy of granulocyte and monocyte adsorption apheresis in the treatment of generalized pustular psoriasis has been proved, very few reports have assessed its efficacy in the treatment of palmoplantar pustulosis and pustulotic arthro-osteitis. Ten pustulotic arthro-osteitis patients with five palmoplantar skin manifestations were treated with weekly granulocyte and monocyte adsorption apheresis over 5weeks. Skin manifestations were assessed using palmoplantar pustulosis area and severity index, and joint symptoms were assessed using a visual analog scale of joint pain, tender joint count, swollen joint count and C-reactive protein immediately before, after and at the 3-month follow up of the five granulocyte and monocyte adsorption apheresis sessions. Two out of five patients with skin manifestations achieved more than 50% improvement in their score (remarkably improved). However, in two patients, deterioration was noted, in one of whom the skin manifestations remained unchanged at the 3-month follow up. In five out of the 10 patients, the joint symptoms were assessed as better than improved at the 3-month follow up. No deterioration was noted at the 3-month follow up. In three patients, reduction or cessation of medication for arthralgia was possible. We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro-osteitis is recalcitrant to conventional therapy.

Adsorption of Soluble Immunoglobulin-Type Adhesion Molecules to Cellulose Acetate Beads.

Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) are elevated in patients with inflammatory bowel disease. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis (GMA). We investigated the effect of CA beads on sICAM-1 and sVCAM-1 plasma concentrations in vitro. Because GM adsorption to CA beads increased with a rise in the incubation temperature in our previous study, peripheral blood was incubated with and without CA beads at 5, 25, 37, or 43 °C and plasma sICAM-1 and sVCAM-1 was measured. The sICAM-1 and sVCAM-1 concentrations in samples incubated with CA beads were significantly lower than those without CA beads at all four temperatures. However, no significant differences were observed both sICAM-1 and sVCAM-1 plasma levels at the four different temperatures after incubation with CA beads. These results suggest that independent of incubation temperature, sICAM-1 and sVCAM-1 are likely to adsorb CA beads. These molecules may be a new index for predicting the therapeutic effects of GMA.

Tu1711 - Safety and Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis in 125 Elderly Patients with Inflammatory Bowel Disease: A Multicenter Cohort Study

Tu1711 - Safety and Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis in 125 Elderly Patients with Inflammatory Bowel Disease: A Multicenter Cohort Study

Pustular psoriasis of pregnancy: current perspectives.

Pustular psoriasis of pregnancy (PPP) is a life-threatening condition for both the pregnant mother and fetus, and must be efficiently and accurately diagnosed and treated. This condition has historically been classified as a unique, separate dermatosis of pregnancy. However, current opinion and data suggest that it may be a variant of generalized pustular psoriasis. PPP typically occurs in the third trimester and is characterized by widespread coalescent pustules, desquamation, and systemic symptoms. Clinical features and histopathologic evaluation aid in diagnosis. Treatments during pregnancy include high-dose corticosteroids, cyclosporine, narrow-band ultraviolet B radiation, infliximab, granulocyte and monocyte adsorptive apheresis, and systemic antibiotics. Both the mother and fetus should be closely monitored with appropriate laboratory studies for the duration of the pregnancy and postpartum.

Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease.

Idiopathic acute-on-chronic inflammation in the gastrointestinal tract is an etiology of inflammatory bowel disease (IBD). Granulocyte and monocyte adsorptive apheresis (GMA) is a nonpharmacological treatment tool for patients with IBD. Here, we present a review of the positioning and possibilities of GMA for patients with IBD. GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

Inhibition of Inflammatory Cytokines and Induction of Myeloid-Derived Suppressor Cells by the Effects of Granulocyte and Monocyte Adsorption Apheresis.

Pro-inflammatory cytokines are involved in the pathogenesis of inflammatory skin diseases attributable to activated neutrophils and macrophages. Myeloid-derived suppressor cells (MDSCs) play an important role in the regulation of the immune response and possess strong immunosuppressive and anti-inflammatory properties. Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument featuring columns containing cellulose acetate (CA) beads, is designed to remove pathogenic myeloid lineage cells. The purpose of this study was to investigate the effects of GMA on cytokine production and MDSC induction. The serum level of various inflammatory cytokines and the incidence of MDSCs in peripheral blood before and after GMA treatment were recorded. Cytokines were assayed with the suspension-array method in 38 patients. The incidence of MDSCs was analyzed by FACS in eight patients and the effect of GMA on in vitro MDSC induction was examined using a mini-column system that mimics GMA. The serum level of IL-2Rα (P = 0.030), IL-8 (P = 0.018), and MIF (P = 0.0002) was significantly decreased by GMA and the incidence of MDSCs was increased (P = 0.030). With the mini-column system, MDSCs were induced in the peripheral blood of five healthy volunteers; the in vitro induction was significantly inhibited by inactivation of the complement component iC3b. The clinical effectiveness of GMA may be attributable to the inhibition of pro-inflammatory cytokines and the induction of anti-inflammatory MDSCs by iC3b activation via the CA beads in the GMA column.

379 Granulocyte and monocyte adsorption apheresis is effective for refractory netrophilic disorders and induces myeloid-derived suppressor cells

Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal apheresis unit designed to remove pathogenic myeloid lineage cells. GMA involves a column containing cellulose acetate (CA) beads that serve as adsorptive leukocyte apheresis carriers. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population comprised of cells at several stages of myeloid lineage differentiation, that differentiate into macrophages, neutrophils, and dendritic cells. MDSCs play an important role in the regulation of the immune response and have immunosuppressive and anti-inflammatory properties. We previously demonstrated that CA beads activate complement component iC3b. Recently, iC3b was shown to induce differentiation of myeloid cells to MDSCs. Based on these facts, we hypothesized that GMA induces MDSC differentiation. The purpose of this study was to investigate the clinical effectiveness of GMA for neutrophilic skin diseases and related arthropathy including pustular psoriasis and psoriatic arthritis and whether GMA induces MDSC. For the assessment of clinical effectiveness, 68 patients with skin lesions and 41 with arthropathy were enrolled. Skin and joint lesions were assessed by overall lesional assessment (OLA) and visual analog scale (VAS), respectively. The incidence of MDSCs was analyzed by FACS in 8 patients and the effect of GMA on MDSC induction was examined using an in vitro mini-column system that mimics GMA. GMA was effective in 56 of 68 patients (82.4%) with skin lesions and 36 of 41 (87.8%) with arthropathy. The incidence of MDSCs in the patients was significantly increased by GMA. In the in vitro mini-column system, MDSCs were induced in the blood of 5 healthy volunteers and the induction was inhibited by inactivation of iC3b. GMAis effective for neutrophilic disorders and the effect might be attributed, at least in part, to the induction of MDSCs via iC3b activation by the CA beads in the GMA column.

Effect of Temperature on Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads.

Granulocyte and monocyte (GM) adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including inflammatory bowel disease (IBD). During GMA, the blood of a patient with IBD passes through a column to contact cellulose acetate (CA) beads at a temperature below body temperature, likely close to room temperature. Here we investigated the effect of temperature on GM adsorption to CA beads in vitro. We incubated peripheral blood with and without CA beads at 5°C, 25°C, 37°C, and 43°C and calculated the ratios of adsorbed GMs. The ratios of adsorbed GMs increased as the temperature was raised. Additionally, we measured complement activation fragment concentrations. C3a and C5a concentrations also increased as the temperature was raised, and C5a concentrations had a positive correlation with the ratios of adsorbed GMs. These results suggest that warming the column during GMA might increase GM adsorption to CA beads, thereby enhancing the clinical efficacy of GMA.

Mo1730 - Higher Expression of MIP-1β and IL23 in Colonic Mucosa of Pretreatment may Predict Therapeutic Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Elderly Patients with Ulcerative Colitis

Mo1730 - Higher Expression of MIP-1β and IL23 in Colonic Mucosa of Pretreatment may Predict Therapeutic Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Elderly Patients with Ulcerative Colitis

Granulocyte and monocyte adsorptive apheresis ameliorates sepsis in rats

BackgroundOverwhelming activation of granulocytes and monocytes is central to inflammatory responses during sepsis. Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads and selectively adsorbs granulocytes and monocytes from the peripheral blood.MethodsIn this study, septic rats received the GMA treatment for 2 h at 18 h after cecal ligation and puncture.ResultsGMA selectively adsorbed activated neutrophils and monocytes from the peripheral blood, reduced serum inflammatory cytokine expression, and seemed to improve organ injuries and animal survival. GMA potentially reduced lung injury by alleviating the infiltration of inflammatory cells and the secretion of cytokines.ConclusionsThis study showed that selective granulocyte and monocyte adsorption with cellulose acetate beads might ameliorate cecal ligation and puncture (CLP)-induced sepsis and improve survival and organ function.

顆粒球吸着療法が奏効した壊疽性膿皮症合併潰瘍性大腸炎の一例

A 30-years-old woman was admitted due to chronic diarrhea and foot ulcer. Her clinical grounds and colonoscopic findings were compatible with ulcerative colitis (UC) . The foot ulcer was aseptic, and histopathological examination of the ulcer base showed nonspecific inflammation with neutrophil infiltration and pseudovasculitis ; pyoderma gangrenosum (PG) was hence diagnosed as an extraintestinal complication of UC. We initiated treatment with 5-aminosalicylate (5-ASA) 4,000 mg/day and granulocyte and monocyte adsorption apheresis (GMA) . The response to the treatment was favorable and rapid-acting. After 10 GMA sessions she achieved remission from UC and PG was completely epithelized. We reduced 5-ASA to 3,000 mg/day and continued observation. This report demonstrates the efficacy of GMA for PG in line with recent studies.

Efficacy and Usefulness of New Single-Needle Intensive Granulocyte and Monocyte Adsorptive Apheresis in Active Ulcerative Colitis Patients Without Corticosteroids and Biologics.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

Effect of Cellulose Acetate Beads on Interleukin-23 Release.

Interleukin (IL)-23, which is released by activated monocytes and neutrophils, promotes production of high levels of IL-17 by T-helper 17 cells. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis using Adacolumn. Contact between blood and CA beads induces cytokine release; however, their inflammatory effects on IL-23 release are unclear. We aimed to clarify the effect of CA beads on IL-23 release in vitro. We incubated peripheral blood with and without CA beads and measured IL-23. Compared to blood samples incubated without CA beads, blood samples incubated with CA beads had significantly decreased amounts of IL-23. In conclusion, CA beads inhibited IL-23 release from adsorbed GMs. The biological effects of this decrease in IL-23 release during GM adsorption to CA beads need further clarification.

Faecal lactoferrin is a useful biomarker for mucosal healing in patients with ulcerative colitis during granulocyte and monocyte adsorptive apheresis therapy.

The study investigated the value of faecal lactoferrin as a follow-up biomarker for mucosal healing of ulcerative colitis during granulocyte and monocyte adsorptive apheresis (GMA) therapy. Patients with ulcerative colitis exhibiting a moderate or severe disease activity with a partial Mayo Score (pMS) of over 4 were enrolled in this study. The patients received 10 courses of GMA therapy. The pMS value and faecal lactoferrin level were monitored and compared with the findings of endoscopy until 12months after the last dose of GMA therapy. Twenty patients (male:female 11:9) were enrolled in this study. Twelve had total colitis, while six had left-sided involvement and two had distal proctitis. Thirteen (65.0%) responded to GMA therapy. The faecal lactoferrin levels were significantly decreased in patients who responded to GMA therapy (P<0.05), whereas the levels did not change in non-responders. Moreover, the faecal lactoferrin levels correlated with the endoscopic findings (r=0.792, P<0.01) and pMS scores (r=0.529, P<0.01). The correlation coefficients between the faecal lactoferrin levels and mucosal findings were higher than those observed between the pMS score and mucosal findings. The faecal lactoferrin level is a useful biomarker of the mucosal findings in ulcerative colitis. Although endoscopy is the gold standard, the faecal lactoferrin level can be used as a biomarker during GMA therapy in patients with ulcerative colitis.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection

BackgroundGranulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. MethodsCombination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. ResultsAll cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3–21 days) and 17 days (median, 6 days; range, 3–17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. ConclusionsThis case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

P643. Safety and efficacy of daily granulocyte and monocyte adsorptive apheresis in 50 consecutive patients with active ulcerative colitis: a prospective study

P643. Safety and efficacy of daily granulocyte and monocyte adsorptive apheresis in 50 consecutive patients with active ulcerative colitis: a prospective study

P560. Concomitant granulocyte and monocyte adsorption apheresis accelerates clinical efficacy and mucosal healing of colonic lesions in patients with active Crohn’s disease

P560. Concomitant granulocyte and monocyte adsorption apheresis accelerates clinical efficacy and mucosal healing of colonic lesions in patients with active Crohn’s disease

An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease.

BackgroundGranulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.MethodsIn an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).ResultsOf the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.ConclusionsIn this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0390-3) contains supplementary material, which is available to authorized users.

Successful treatment of neutrophilic dermatosis in patient with Crohn's disease with granulocyte and monocyte adsorption apheresis

Successful treatment of neutrophilic dermatosis in patient with Crohn's disease with granulocyte and monocyte adsorption apheresis