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Tu1292 EFFICACY OF GRANULOCYTE AND MONOCYTE ADSORPTIVE APHERESIS TREATMENT IS CORRELATED WITH COLONIC MUCOSAL EXPRESSION OF TH17-ASOCIATED CYTOKINES IN ULCERATIVE COLITIS

Chie Kurihara, Toshihide Ohmori, Kenichi Inaba, Shunsuke Komoto, Kengo Tomita, Ryota Hokari Gastroenterology 2020 158 (6) Suppl.S-1046

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood, and it is used as induction therapy for IBD. However, its therapeutic mechanism has not been well characterized. Recently, it has been reported that Th17 releases chemokines which attract neutrophils, and some neutrophils produce IL17. We investigated that changes in mRNA expression levels of inflammation associated molecules such as cytokines, chemokines in colonic mucosa of ulcerative colitis (UC) patients before and after GMA treatment in order to obtain further understanding of GMA therapeutic mechanisms. Methods: Thirty-two active UC patients (Mayo score ≥ 5 and Mayo endoscopic score ≥ 2) and 10 non-IBD control subjects were enrolled in this study. All UC patients received 10 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Control subjects underwent colonoscopies for screening of colon cancer. Assessment of GMA therapeutic efficacy was determined based on Mayo score. Inflammation-related molecules mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: GMA treatment efficacy is 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) were response and 4 patients (12.5%) were non-response. Baseline characteristics such as sex, location of disease, CRP, WBC and Mayo score were not significantly different according to GMA efficacy. In the remission group, mRNA levels in mucosal tissue of IL1β, IL6, IL17, IL23 and GM-CSF which are Th17-asociated cytokines significantly decreased after the last GMA compared to the baseline levels(P<0,05) in contrast, expression of these mRNA tended to increase following GMA treatment in the non-response group. On the other hand, IL12 and IFN- γ which are associated with Th1 did not significantly decrease in the remission group. mRNA levels of leukocyte trafficking associated molecules such as MAdCAM-1, ICAM-1, integrinβ7, IL8 and MIP-1β significantly decreased following GMA treatment in the remission group(P <0.05), whereas only IL8 mRNA expression in the non-response group tended to increase. IL1 β, IL6, GM-CSF which are Th17-asociated cytokines and IL8 mRNA expressions in post-GMA treatment were significantly higher in the non-response group compared to the remission group or control group(P <0.05). Conclusion: In UC patients who achieved clinical remission by GMA, Th17- associated cytokines and leukocyte trafficking associated molecules but not Th1-asociated cytokines decreased significantly. Furthermore, Th17-asociated cytokines increased in the non-responders. These results reaffirm the involvement of neutrophil in the pathophysiology of UC and could be helpful for characterizing of GMA therapeutic mechanism.

https://www.gastrojournal.org/article/S0016-5085(20)33300-X/pdf

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Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders.

Takuro Kanekura 1, J Dermatol 2018 Aug;45(8):943-950

These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.

https://pubmed.ncbi.nlm.nih.gov/29782055/

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Mucosal Cytokine Profiles After Induction Therapy With Granulocyte/Monocyte Apheresis in New-onset Inflammatory Colitis.

Helena Rolandsdotter 1 2Kerstin Jönsson-Videsäter 3 4Ulrika L Fagerberg 5 6Michael Eberhardson 1 7Yigael Finkel 1 2 , J Pediatr Gastroenterol Nutr. 2018 Apr;66(4):e103-e107.

We speculate that the decreases in colonic mucosal cytokine profiles after treatment may explain the observed clinical efficacy in the GMA-treated children with IBD.

https://pubmed.ncbi.nlm.nih.gov/28891831/

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Adsorptive granulocyte/monocyte apheresis use in severe ulcerative colitis and determination of changes in plasma cytokines.

Belén Beltrán 1 2 3Esteban Sáez-González 1Inés Moret 1 2 3Francia C Díaz-Jaime 1Diego Alvarez-Sotomayor 1Elena Cerrillo 1 2Marisa Iborra 1 2 3Guillermo Bastida 1 2 3Mariam Aguas 1 2 3Pilar Nos 1 2 3 , J Clin Apher. 2018 Feb;33(1):99-103

We hypothesize that GMA can help to lower the inflammatory load, thereby enhancing the effect of biologic drugs. 

https://pubmed.ncbi.nlm.nih.gov/28485025/

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

Shingo KatoAkira IshibashiKaori SugiuraKazuhito KaniTomonari OgawaHajime HasegawaKoji Yakabi, Contrib Nephrol 2018;196:200-208.

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.

https://pubmed.ncbi.nlm.nih.gov/30041228/

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Cytapheresis (CAP) with leukocyte removal filter/bead column as onetherapeutic option for inflammatory bowel disease

Koji Sawada 1 , Transfus Apher Sci. 2017 Oct;56(5):689-697.

Clinical studies with these two new models have shown good effects for active IBD. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy of IBD, to promote remission, taper conventional drug dosage and potentially should reduce the number of patients who require colectomy. The results may further understandings of the pathophysiology of IBD and this in turn should contribute to a more effective treatment of this disorder.

https://pubmed.ncbi.nlm.nih.gov/28986009/

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Sequential therapy consisting of glucocorticoid infusions followed by granulocyte-monocyte absorptive apheresis in patients with severe alcoholic hepatitis.

Kazuhiro Watanabe 1Yoshihito Uchida 1Kayoko Sugawara 1Kayoko Naiki 1Mie Inao 1Nobuaki Nakayama 1Satoshi Mochida 2 , J Gastroenterol 2017 Jul;52(7):830-837.

Sequential therapy combining glucocorticoid infusion and GMA was useful for attenuating liver injuries in patients with severe alcoholic hepatitis by preventing rebound increases in inflammatory reactions after discontinuation of glucocorticoid infusions, except in patients with bacterial infections and/or multiple organ failure.

https://pubmed.ncbi.nlm.nih.gov/27858246/

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

Masanao Sakanoue 1Yuko Higashi 1Takuro Kanekura 1 ,Ther Apher Dial. 2017 Dec;21(6):628-634.

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.

https://pubmed.ncbi.nlm.nih.gov/28941055/

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Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease.

Esteban Sáez-González 1Inés Moret 2 3 4Diego Alvarez-Sotomayor 2Francia Carolina Díaz-Jaime 2Elena Cerrillo 2 3Marisa Iborra 2 3 4Pilar Nos 2 3 4Belén Beltrán 2 3 4 , Dig Dis Sci. 2017 Jun;62(6):1417-1425.

The benefit of cytapheresis appears to rest upon its ability to reduce levels of certain immune cell populations; however, whether this depletion results in further changes in lymphocyte populations and cytokine production needs further clarification. In this review, we aim to summarize existing evidence on the role of cytapheresis in patients with IBD, its effect on cytokine levels and cellular populations, and to discuss its potential impact on disease activity.

https://pubmed.ncbi.nlm.nih.gov/28432476/

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