Granulocyte And Monocyte Adsorption Apheresis Research Articles

Granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: A useful therapeutic tool not just in ulcerative colitis but also in Crohn's disease

IntroductionGranulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn's disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission. Patients and methodRetrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions. ResultsWe treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD. ConclusionsGMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Successful treatment with granulocyte and monocyte adsorption apheresis for plaque-type skin lesions in patients with psoriatic arthritis.

Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly for refractory skin diseases, such as generalized pustular psoriasis and psoriatic arthritis (PsA). Four patients with PsA who were refractory to previous treatments were enrolled. They received five or ten sessions of GMA. We assessed the clinical conditions of each patient and laboratory findings before and after GMA. GMA was effective in plaque-type skin eruptions in all four patients with PsA. It was also effective in joint symptoms in three patients with PsA with mild symptoms, but was ineffective in one patient with severe joint symptoms. GMA may be recommended to PsA patients with skin eruptions and mild joint symptoms.

P511 Short-term real-world effectiveness and safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: GRACE Study

Abstract Background The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn's disease (CD) pts who were underrepresented in CT is still limited. Methods GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of pts and their management and outcome 4 weeks after GMA treatment. Results A total of 95 evaluable pts were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of pts had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 pts (10.6%) with CD, all had B1, and 3 pts had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of pts had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of pts received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 pts reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed. Conclusion Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory pts with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of pts were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.

The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn's disease: A multicenter retrospective pilot study.

A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.

Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis.

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis

To the Editor: Generalized pustular psoriasis (GPP) often requires urgent treatment such as biologics.1 However, the safe administration of a biologic typically requires laboratory testing, which presents a timeliness issue because most tests take a few days to return results (eg, 4 business days for the commercial T-Spot.TB test). Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes, which can be easily introduced in clinics and hospitals where hemodialysis is performed.

Granulocyte and monocyte adsorptive apheresis for pyoderma gangrenosum.

Pyoderma gangrenosum (PG), a chronic aseptic inflammatory skin disease characterized by skin ulcers with elevated and undermined borders, is resistant to conventional therapies. PG is elicited by activated neutrophils and macrophages and is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, aortitis syndrome, and hematopoietic disorders. This single-center study assessed the efficacy and safety of selectively depleting myeloid-lineage leukocytes in patients with PG. Patients with PG, aged 20 or over, received 5 or 10 treatment sessions of granulocyte and monocyte adsorption apheresis (GMA), once or twice a week. Treatment efficacy was assessed based on the rate of skin ulcer reduction, the visual analog scale of pain, and the physician's global assessment of the skin lesions. A complete response (CR) was obtained in eight patients, a nearly complete response (nCR) in three patients, and a partial response (PR) in two patients. In four of the other six, the disease remained stable (SD) and in two we observed disease progression (PD). No severe adverse events were recorded. Our results suggest that GMA is a useful and safe treatment modality for PG.

Physiological heating augments the anti‐inflammatory reactions during granulocyte/monocyte apheresis: A in vitro study

Granulocyte and monocyte adsorptive apheresis (GMA), an effective therapy for inflammatory disorders, exerts an anti-inflammatory influence by utilizing the biological reaction between blood and cellulose acetate (CA) beads, which are the carriers of the GMA column. Although the biological reaction has an optimum temperature, blood contacts the CA beads below body temperature as GMA is performed in an extracorporeal circulation system. We investigated various soluble factors in blood treated with CA beads at 25°C and 37°C. Here, the optimal temperature for IL-1 receptor antagonist (IL-1ra) release induced by CA beads was 37°C, and IL-6 production from monocytic cells was inhibited by the addition of plasma prepared from the CA bead-treated blood at 37°C, rather than at 25°C. These results indicated that physiological heating of the apheresis carrier augmented the anti-inflammatory reaction in vitro. Thus, heating during GMA may be a new approach for augmenting clinical efficacy.

Factors associated with the outcomes in ulcerative colitis patients undergoing granulocyte and monocyte adsorptive apheresis as remission induction therapy: A multicenter cohort study.

Ulcerative colitis (UC) patients harbor activated myeloid leukocytes, which exacerbate and perpetuate UC by releasing inflammatory cytokines. Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn depletes elevated myeloid leukocytes, inducing efficacy with favorable safety. To understand how the clinical outcome with GMA is affected by prior corticosteroid treatment or concomitant immunomodulators, a retrospective multicenter study in 102 UC patients, who had not responded well to first-line medications was undertaken. The remission rates after a course of GMA therapy were significantly higher in corticosteroid-naïve patients compared with those with prior corticosteroid exposure. Absence of corticosteroid background was an independent predictive factor of response to GMA. Further, in corticosteroid-naïve patients, the 1-year cumulative sustained remission rate in patients who did not receive immunomodulators was significantly higher than in patients who received immunomodulators. Accordingly, multivariate analysis revealed that immunomodulator was associated with higher risk of relapse. In conclusion, GMA was an effective treatment for corticosteroid-naïve patients and the efficacy sustained longer in those not receiving immunomodulators during GMA. GMA fulfills the notion that apheresis is to induce disease remission by removing from the body factors known to perpetuate disease. In therapeutic settings, these findings should help better decision making and avoid futile use of medical resources.

Intensive granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis.

Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly (consisting of five sessions) for refractory skin diseases, such as generalized pustular psoriasis (GPP). The time to remission of inflammatory bowel diseases has been reported to be significantly shorter in intensive GMA (twice a week) than in regular GMA (once a week). Despite several reports of GPP cases treated with intensive GMA, the efficacy of intensive GMA has not been verified in GPP. Herein, we present two GPP patients with a mutation in the IL36RN gene, who initially received regular GMA, and intensive GMA upon recurrence. There were no adverse effects during regular and intensive GMA for both patients. Because concomitant medication was only prednisolone (20mg/day) during regular and intensive GMA, intensive GMA showed superiority to regular GMA in patient 1. Although concomitant medications were different between regular and intensive GMA in patient 2, these drugs had been used before the start of each GMA therapy. We cannot neglect the effects of concomitant drugs, but we observed a shorter time to remission in intensive GMA than that in regular GMA in both patients. More case studies will be necessary for evaluating the clinical efficacy of intensive GMA.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients with Active Ulcerative Colitis During the COVID-19 Outbreak (EXPECT Study): A Multicenter Prospective Clinical Trial

Background: During the COVID-19 pandemic, safe treatment of inflammatory bowel disease is required. Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC) with few adverse events. Therefore, elucidating the effectiveness of GMA without steroids is important in the current situation. The aim of this study was to investigate the effectiveness of GMA in active UC patients who are not receiving steroids. Methods: A single-arm, open-label, and multicenter prospective clinical trial was conducted at ten facilities in Japan.UC patients who had insufficient responses to 5-aminosalicylic acid without steroids received GMA twice a week for five consecutive weeks. The primary and secondary endpoints were the induction of a response and endoscopic mucosal healing in the patients who achieved a response. Findings: A total of 67 patients were enrolled. The response rate of all patients who received GMA ten times was 58·2%. Of the 39 patients who achieved a response, 74·4% achieved endoscopically confirmed mucosal healing. Both the median Mayo score and ulcerative colitis endoscopic index of severity score were significantly decreased in the patients who achieved a response. The response rate of the patients who were suffering from their first episode was significantly higher than that of those with relapse-remitting UC (80·0% [16/20] vs. 48·9% [23/47], p=0·029). Undergoing the first episode of UC (odds ratio [OR]: 4·952, 95% confidence interval [CI]: 1·292-18·981, p>0.001) was defined as an independent predictor of a response. Interpretation: This study strongly suggest that GMA shows promising effectiveness in inducing remission in active UC patients who are not receiving steroid treatment. We expect that GMA can be made available during the COVID-19 pandemic. Trial Registration: UMIN registration No. 000013702 Funding Statement: Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease to HN). Declaration of Interests: MM reports personal fees from Janssen Pharmaceutical K.K., and commercial research funding from AbbVie GK. and Nippon Kayaku Co., Ltd. SN reports receiving personal fees from EA Pharma Co., Ltd., AbbVie GK., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. KH reports receiving research funding from EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. HN reports receiving personal fees from AbbVie GK., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Pfizer Lnc., Cell gene Corporation., EA Pharma Co., Ltd., Zeria Pharmaceutical CO., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Daiichi Sankyo Company, Limited., JIMRO Co., Ltd., as well as grants for commissioned/joint research from Hoya Group Pentax Medical, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. All other authors declare no competing interests. Ethics Approval Statement: The protocol of the clinical trial was approved by the IRB at each institution. Informed consent to participate in the study was obtained from each participant before inclusion.

Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis.

BackgroundThe use of monotherapy with intensive granulocyte and monocyte adsorptive apheresis (GMA) or a Janus kinase (JAK) inhibitor has been limited to patients with refractory ulcerative colitis (UC). The efficacy and safety of combination therapy with tofacitinib (TOF) plus intensive GMA (two sessions per week) for refractory UC have not been evaluated.MethodsThis retrospective study evaluated the 10-week efficacy of combination therapy with TOF plus intensive GMA in patients with refractory UC.ResultsOf seven patients who received a combination therapy with TOF plus intensive GMA, 71.4% achieved clinical remission at 10 weeks. The percentages of patients with mucosal healing and complete mucosal healing at 10 weeks were 100% and 42.9%, respectively. The mean full Mayo score and endoscopic subscore at baseline were 8.71 ± 0.80 and 2.4 ± 0.2, respectively, and the corresponding values at 10 weeks were 1.57 ± 0.48 and 0.6 ± 0.2 (P < 0.01), respectively. Adverse events of an orolabial herpes and temporary increase in creatinine phosphokinase (CK) and triglyceride were observed in three patients.ConclusionsBased on these outcomes, combination therapy with TOF plus intensive GMA was well tolerated and may be useful for induction of clinical remission in patients with refractory UC.

Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study

BackgroundThe available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations.MethodsThis study included patients with ulcerative colitis (UC) or Crohn’s disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2.ResultsA total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC.ConclusionsThe incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

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.

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.