Scientific corner

Faecal calprotectin level for assessing endoscopic activity and predicting future clinical course in patients with moderately active ulcerative colitis undergoing granulomonocytapheresis: a prospective cohort study

Takahiro Shimoyama 1Takayuki Yamamoto 2Satoru Umegae 1Koichi Matsumoto 1 , BMC Gastroenterol. 2018 Aug 1;18(1):120.

Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

Scientific corner

Granulocyte and monocyte adsorptive apheresis ameliorates sepsis in rats.

Shuai Ma 1Qingqing Xu 1Bo Deng 1Yin Zheng 2Hongyan Tian 1Li Wang 3Feng Ding 4 , Intensive Care Med Exp. 2017 Dec;5(1):18.

This 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.

Scientific corner

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

Shoichi Nishise 1Yuji Takeda 2Yasuhiko Abe 1Yu Sasaki 1Hidetoshi Nara 2Hironobu Asao 2Yoshiyuki Ueno 1 , Ther Apher Dial. 2017 Jun;21(3):248-254.

These results suggest that warming the column during GMA might increase GM adsorption to CA beads, thereby enhancing the clinical efficacy of GMA.

Scientific corner

A Case of Old Age-Onset Generalized Pustular Psoriasis with a Deficiency of IL-36RN (DITRA) Treated by Granulocyte and Monocyte Apheresis.

Chiharu Tominaga 1Masaaki Yamamoto 1Yasutomo Imai 1Kiyofumi Yamanishi 1 , Case Rep Dermatol. 2015 Feb 21;7(1):29-35.

 She is the oldest reported case of GPP with a deficiency of interleukin-36 receptor antagonist (DITRA), although GPP in DITRA has been suggested to usually occur in younger cases with no pre-existing psoriasis vulgaris.

Scientific corner

Advantages of Fecal Lactoferrin Measurement during Granulocyte and Monocyte Adsorptive Apheresis Therapy in Ulcerative Colitis.

Keiichi Hashiguchi 1Fuminao TakeshimaYuko AkazawaKayoko MatsushimaHitomi MinamiHaruhisa MachidaNaoyuki YamaguchiKen ShiozawaKazuo OhbaKen OhnitaTatsuki IchikawaHajime IsomotoKazuhiko Nakao, Digestion. 2015;91(3):208-17.

Background: Fecal lactoferrin has been introduced as a useful tool for the diagnosis and monitoring of inflammatory bowel disease (IBD). The aim of this study was to assess if fecal lactoferrin can be employed to predict or estimate the effect of granulocyte and monocyte adsorptive apheresis (GMA) in ulcerative colitis (UC). Methods: This was a prospective study involving 21 patients with UC. Patients with moderately-to-severely active UC who were scheduled to undergo GMA were recruited. Changes in fecal lactoferrin concentration were compared between the GMA-responder and -nonresponder groups. Results: In the GMA-responder group, fecal lactoferrin significantly increased 1 week after the introduction of GMA and then significantly decreased after GMA sessions. Fecal lactoferrin concentrations were significantly higher in the GMA-responder group than in the GMA-nonresponder group at 1 and 2 weeks after the introduction of GMA. Multivariate logistic regression analysis revealed that fecal lactoferrin concentration 1 week after the introduction of GMA was the most contributing factor for the effectiveness of GMA in patients with UC. Conclusions: In the GMA-responder group, fecal lactoferrin concentration significantly increased 1 week after the introduction of GMA. Fecal lactoferrin may be beneficial for predicting clinical response of GMA in patients with UC at an early stage of GMA treatment.

Scientific corner

Granulocyte and Monocyte Adsorption Apheresis for Refractory Skin Diseases due to Activated Neutrophils, Psoriasis, and Associated Arthropathy.

Masanao Sakanoue 1Koichiro TakedaKazuhiro KawaiTakuro Kanekura, Ther Apher Dial. 2013 Oct;17(5):477-83.

Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is designed to remove activated granulocytes and monocytes. We previously demonstrated that GMA was useful for treating neutrophilic dermatoses and associated arthropathy as it adsorbs Mac-1 (CD11b/CD18)-expressing neutrophils to the CA beads by the binding of complement component (iC3b) and CD11b expressed on activated neutrophils. The objective of this study is to further assess the clinical effectiveness of GMA in the treatment of neutrophilic dermatoses and associated arthropathy. The effect of GMA for skin lesions and joint lesions was assessed in 44 and 23 patients, respectively. Mac-1 expression on peripheral neutrophils was measured by flow cytometry. Skin lesions and arthropathy improved in 39 of 44 patients (88.6%) and 22 of 23 (95.6%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, 27.1 ± 6.66 MFI (mean fluorescence intensity) before treatment, was reduced to 17.9 ± 3.02 MFI by GMA (P < 0.05). Clinical effectiveness of GMA for the treatment of intractable neutrophilic dermatoses and associated arthropathy was further confirmed.

Scientific corner

Production of Interleukin-10 by combining a granulocyte and monocyte adsorption carrier with ulinastatin.

Shoichi Nishise 1Takeshi SatoYu SasakiKo NaginoDaisuke IwanoTakao YaoitaKazuya YoshizawaYuko NishiseHiroaki Takeda, Ther Apher Dial. 2012 Oct;16(5):449-55.

Interleukin (IL)-10 is an anti-inflammatory cytokine mainly produced by monocytes and is essential for the induction of anti-inflammatory intestinal macrophages with macrophage colony-stimulating factor (M-CSF). Thus, IL-10- and M-CSF-rich conditions in colonic tissues seem to contribute to the improvement of pathological conditions in patients with inflammatory bowel diseases (IBD). We have already reported that ulinastatin, a serine protease inhibitor, increases M-CSF production during granulocyte/monocyte (GM) adsorption to cellulose acetate (CA) beads (carriers for Adacolumn therapy). However, the effects of ulinastatin on IL-10 production have not been clarified. The aim of the present study was to clarify the effects of ulinastatin on IL-10 production during GM adsorption by in vitro experiments. Peripheral blood was divided into four groups: (Control) no ulinastatin added, no contact with CA beads; (1) no ulinastatin added, contact with CA beads; (2) ulinastatin added, no contact with CA beads; and (3) ulinastatin added, contact with CA beads. After incubation, IL-10 in the plasma was measured. Compared with the level in the Control group, plasma IL-10 was significantly higher only in group 3, in which ulinastatin was added in the presence of CA beads, but did not increase in the absence of CA beads. These results suggest that ulinastatin synergistically increases IL-10 production with monocyte adsorption stimuli. By increasing not only M-CSF but also IL-10, a combination of ulinastatin and Adacolumn therapy may improve clinical efficacy for the treatment of IBD in terms of the induction of anti-inflammatory intestinal macrophages.

Scientific corner

Peripheral blood CD64 levels decrease in Crohn’s disease following granulocyte and monocyte adsorptive apheresis.

Toshimi Chibaa, Mikiya Endob, Shoko Matsushitab, Mika Sasakib, Shoichi Chidab, Yosuke Toyaa, Satoshi Kasugaia, Nozomi atsudaa, Shunsuke Orikasaa, Yukito Abikoa, Norihiko Kudaraa, Shuhei Oanaa, Masaki Endoa, Kazuyuki Suzukia© 2011 S. Karger AG, BaselISSN 1662–0631

Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn’s disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI). The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.

Scientific corner

Effects of Cytapheresis on Tumor Necrosis Factor Receptor and on Expression of CD63 in Myeloperoxidase–Antineutrophil Cytoplasmic Autoantibody-associated Vasculitis

Midori Hasegawa 1Chikako NishiiNao KabutanMasao KatoAtsushi OhashiShigeru NakaiKazutaka MurakamiMakoto TomitaKunihiro NabeshimaYoshiyuki HikiHisaji OshimaSatoshi Sugiyama, Ther Apher Dial. 2007 Oct;11(5):337-40.

From these results, the inhibition of TNF action and removal of degranulated granulocytes appear to be related to the mechanism whereby cytapheresis can exert a beneficial and therapeutic function in the treatment of MPO-ANCA-associated vasculitis.

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