H. Hanai, Y. Takeda, M. Eberhardson, R. Gruber, A. R. Saniabadi, O. Winqvist and R. Lofberg, doi:10.1111/j.1365-2249.2010.04279.x

imflammatory cytokines include activated myeloid leucocytes, which in patients with IBD are elevated with activation behaviour,selective depletion of these proinflammatory leucocytes by GMA appears to be an attractive strategy to alleviate inflamamation or enhance the efficacy of pharmacological therapy. However, clinical studies have hitherto reported both impressive as well as disappointing efficacy outcomes, indicating that patients’ demographic factors might determine
responders or non-responders to GMA. Further, as this non drug-based treatment intervention has an excellent safety
profile, it is very much favoured by patients and our impression is that the use of therapeutic GMA will expand rather than diminish. The MoA of GMA appears to be more than physical depletion of excess and activated GM per se; the release of IL-1ra, HGF, sTNF RI, RII and the rise of regulatory CD4+ CD25+ T cells are typical effects which are potentially very interesting in the context of treating conditions that reflect a dysregulated immune profile

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010911/pdf/cei0163-0050.pdf

Mingming Zhu ¹, Xitao Xu, Fang Nie, Jinlu Tong, Shudong Xiao, Zhihua Ran, Int J Colorectal Dis. 2011 Aug;26(8):999-1007.

Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

https://pubmed.ncbi.nlm.nih.gov/21476027/

Kazuko Ikeda, Toshihisa Hamada, Masaki Otsuka, Keiji Iwatsuki, Eur J Dermatol. Sep-Oct 2011;21(5):804-5.

https://pubmed.ncbi.nlm.nih.gov/21752760/

Atsushi Yoshida ¹, Kenji Kobayashi, Fumiaki Ueno, Eiki Yoshimatsu, Keiji Matsui, Tomoaki Fujikawa, Hirohito Shimizu, Kentaroh Takatsuka, Shogo Iwabuchi, Intern Med. 2011;50(1):11-5.

Early application of TAUS may predict the long-term clinical outcome after CAP in patients with active UC.

https://pubmed.ncbi.nlm.nih.gov/21212567/

https://www.jstage.jst.go.jp/article/internalmedicine/50/1/50_1_11/_pdf/-char/en

Shingo Kato, Kazuhito Kani, Hidehiko Takabayashi, Ryuichi Yamamoto, Koji Yakabi Gastroenterology 2011 140(5) Suppl. S-279–S-280

Backgrounds&Aims; Granulocyte and monocyte adsorptive apheresis (GMA) adsorbs mainly granulocyte and monocytes, as well as Leukocyteapheresis (LMA) filters many cells such as granulocyte, monocytes, lymphocytes and platelets. However, there was no significant difference in clinical effectiveness between GMA and LMA (Eur J Gastroenterol Hepatol 2008;20:629). We hypothesized effectiveness of GMA and LMA might be dependent on depletion of granulocyte and monocytes. S100A12 was reported to be exclusively expressed in neutrophils and up-regulated by TNF α. The aim of this study was to investigate the changes of serum S100 A12 concentration in the GMA treatments and whether S100A12 increases the expression of adhesion molecules, CXCL and CCL chemokines. Methods; 24 patients with ulcerative colitis were treated with GMA. Serum S100A12 was estimated by ELISAmethods.Clinicalactivityindex(CAI)andserumCRPconcentrationwerealsochecked. Immunohistochemical staining of S100A12 and receptor for advanced glication end products (RAGE) were performed in the operated specimens of patients with ulcerative colitis and with colonic carcinoma (control). HUVEC were seeded into 12 well plates and confluent plates were used to experiments. Each experiment was performed in triplicate. HUVEC were treated with human recombinant S100A12 protein. RNA was extracted by RNeasy Mini Kit. 1.5μg RNA was reverse-transcriptated into cDNA. ICAM-1, VCAM-1, IL-8, CCL-2 (MCP1), CCL5 (RANTES), CXCL9 (IP-10) and CXCL10 (Mig) mRNA was quantitated by realtime PCR. Results; S100A12 staining was faintly recognized in the mucosal layer of normal control. S100A12 staining was increased in infiltrating cells in inflamed colon in patients with ulcerative colitis. Strong staining was also recognized in crypt abscess. RAGE staining was also faintly recognized in the epithelial cells in nornmal control. However, RAGE staining was increased in the inflamed epithelial cells. Significantly serum S100A12 concentration was positively correlated with CAI (n=34, p=0.02, rs=0.404). 16 patients were able to estimate S100A12 concentration in the points of pre-and post-GMA treatment. 13 patients wereGMA-respondersand3patientswere nonGMA-responders.SerumS100A12concentration was significantly decreased in GMA responders (pre-vs post-GMA, 1.34±1.08 vs 0.60±0.50, p<0.05). However, Serum S100A12 concentration of non GMA-responders was gradually increased with GMA treatments. ICAM-1, VCAM-1, IL-8, IP-10, Mig, MCP-1 and RANTES mRNA expressions were increased by S100A12 in HUVEC cell lines in time and dose-dependent manners. Conclusion; one of the mechanisms of GMA effect might be correlated with depletion of S100A12 by adsorption of activated neutrophils. S100A12 might aggravate acute and chronic inflammation by up-regulation of adhesion molecules, CXCL and CCL chemokines.

Stefano Passalacqua ¹, Pietro Manuel Ferraro, Giampaolo Bresci, Valeria D’Ovidio, Marco Astegiano, Mariabeatrice Principi, Roberto Testa, Renata D’Incà, Daniela Valpiani, Alessandro Armuzzi, Renato Sablich, Flaminia Cavallaro, Francesco Costa, Vincenza Di Leo, Elisabetta Colombo, Alessia Santini, Annalisa Aratari, Pierenrico Lecis, Valeria Saladino, Gabriele Riegler, Marino Marco, Francesca Calella, Chiara Ricci, Maria Luisa Guidi, Giuseppe Repaci, Michele Silla, J Clin Apher. 2011 Dec;26(6):332-7.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte-monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn’s disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn’s disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered.

https://pubmed.ncbi.nlm.nih.gov/22072543/

Takuya Yoshino ¹, Hiroshi Nakase, Minoru Matsuura, Kayoko Matsumura, Yusuke Honzawa, Takumi Fukuchi, Kenji Watanabe, Mitsuyuki Murano, Tomoyuki Tsujikawa, Ken Fukunaga, Takayuki Matsumoto, Tsutomu Chiba, Digestion. 2011;84(1):3-9.

The colectomy ratio tends to be high in refractory UC patients with recurrent CMV reactivation or infection. Therefore, GMA might be a safe and effective treatment for UC patients positive for CMV because it does not induce CMV reactivation.

https://pubmed.ncbi.nlm.nih.gov/21311190/

https://repository.kulib.kyoto-u.ac.jp/dspace/handle/2433/183987

Stephan Vavricka, Digestion. 2011;84(1):1-2. doi: 10.1159/000322434.

https://pubmed.ncbi.nlm.nih.gov/21311189/

Toshifumi Ashida ¹, Yutaka Kohgo, Akihiro Munakata, Mitsunori Noguchi, Bunei Iizuka, Yutaka Endo, Hiroyuki Hanai, Toshikazu Yoshikawa, Takayuki Matsumoto, Nobuo Aoyama, Toshiyuki Matsui, Keiichi Mitsuyama, Toshifumi Hibi

Transfus Apher Sci 2011 Apr;44(2):113-7. doi: 10.1016/j.transci.2011.01.001.

We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger’s clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.

https://pubmed.ncbi.nlm.nih.gov/21402309/

Nobuhito Kashiwagi

Japanese Journal of Apheresis 30(1): 39-47, 2011