UEG WEEK VIRTUAL 2021

GMA induces specific immunoregulatory changes in leukocyte’s subpopulations. We confirm the depletion of the
monocytes with proinflammatory phenotype after GMA. Treg and B effector cells shift to a more immunotolerant phenotype. The emergence of subpopulations with the atypical immunofluorescence staining (CXCR3+CRTH2+) related to immature T cells support the immunomodulatory effects of GMA. These findings could help to understand the pathology of UC and to identify targeted immune subpopulations for treatment

P0246 UEG.pdf

Ailing Song, Hai Jiang, Liang Guo, Shanshan Wu, Am J Transl Res 2021;13(5):5156-5164

Objectives: The study discussed and analyzed the combined efficacy of adalimumab with granulocyte and monocyte adsorption apheresis (GMA) method on patients with ulcerative colitis (UC) and the repair of intestinal mucosal lesion. Methods: 60 UC patients in moderate-to-severe active phase that hospitalized from January 2017 to March 2020 were chosen and randomly classified into observation group (n=30) and control group (n=30). The control-group patients received GMA treatment, and the observation-group patients received combination therapy of GMA and adalimumab. The therapeutic efficacy, laboratory indicators, changes of serum inflammatory factors, and intestinal mucosal barrier impairment in two sets of participants were compared. Results: The comprehensive effective rate of clinical treatment was remarkably higher in observation group than that in control group (P<0.05). CRP and ESR of the two groups in post- treatment were notably lower than those before treatment (P<0.05), while Hb and ALB in post-treatment increased significantly than in pre-intervention (P<0.05); CRP in observation group after treatment was remarkably lower than that in control group (P<0.05), while no significant difference was noticed in ESR, ALB and Hb between the two groups (P>0.05). The serum inflammatory factors in observation group in post-treatment were significantly lower than those in the control group (P<0.05). The scores of PCT, DAO and intestinal mucosa in two sets of participants in post-treatment were dramatically lower than those in pre-treatment (P<0.05), and the scores in observation group after treatment were notably lower than those in the control group (P<0.05). Conclusions: The combined efficacy of adalimumab with GMA on UC patients can improve the clinical curative efficacy, effectively reduce the inflammatory factors, which is beneficial to the repair of intestinal mucosal barrier function, and worthy of clinical application.

https://pubmed.ncbi.nlm.nih.gov/34150104/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205815/pdf/ajtr0013-5156.pdf

Eugeni Domènech, Joan-Ramon Grífols, Ayesha Akbar, and Axel U Dignass World J Gastroenterol. 2021 Mar 14; 27(10): 908–918.

GMA is the only available therapy for UC directly targeting neutrophils. Two controlled, multicentre, European studies and a number of recent cases series found a potential therapeutic benefit of GMA in different clinical scenarios of UC with a still unmet need for optimal treatment. Moreover, GMA has an excellent safety profile and is perceived as a convenient procedure by patients, making this non-pharmacological therapy a suitable alternative or add-on therapy in UC, particularly for frail or comorbid patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968132/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968132/pdf/WJG-27-908.pdf

Miki Koroku ¹, Teppei Omori ¹, Harutaka Kambayashi ¹, Shun Murasugi ¹, Tomoko Kuriyama ¹, Yuichi Ikarashi ¹, Maria Yonezawa ¹, Ken Arimura ², Kazunori Karasawa ³, Norio Hanafusa ⁴, Masatoshi Kawana ⁵, Katsutoshi Tokushige ¹ Intest Res. 2021 Mar 12. doi: 10.5217/ir.2020.00148.

In conclusion, our patient’s case indicates that GMA for a patient with both active UC and COVID-19 is a safe treatment option for active UC that could lead other patients in this condition to remission.

https://pubmed.ncbi.nlm.nih.gov/33902268/

https://irjournal.org/upload/pdf/ir-2020-00148.pdf

Nobuhito Kashiwagi , Fumio Saito , Hidetaka Maegawa , Kenta Kaneda, Cytokine 2021 Mar;139:155410.

Objective: Apoptotic cells participate in maintenance of homeostasis of the adaptive immune system. Granulocyte/monocyte adsorptive apheresis (GMA) performed with an Adacolumn has been shown to have clinical efficacy together with immunomodulatory effects for immune-mediated disorder cases, such as inflammatory bowel disease (IBD) or psoriatic arthritis. Although induction of apoptosis in neutrophils by GMA has been observed, the detailed mechanism remains unclear. Methods: To focus on phagocytosis-induced cell death (PICD) that induces apoptotic neutrophils, a comparative study utilizing a GMA-carrier (leukocyte adsorbing carrier for Adacolumn) and yeast particles was performed with in vitro and in vivo examinations. Results: L-selectin was significantly (P = 0.0133) shed, reactive oxygen species (ROS) production was promoted (P = 0.0019), and apoptosis induction was enhanced (P = 0.0087) by peripheral blood co-cultured with the GMA-carrier or yeast particles as compared to incubated blood alone. Furthermore, degranulation of myeloperoxidase, elastase, and lactoferrin was increased by both treatments, while the highest level of interleukin-1 receptor antagonist release was found with GMA-carrier treatment (P = 0.0087) as compared to the yeast particles. Plasma from blood treated with the GMA-carrier showed chemotactic activity, and suppressed neutrophil migration to IL-8 and LTB₄. In vivo results demonstrated that neutrophil chemotaxis to IL-8 was desensitized (P = 0.0078) in rabbits following GMA apheresis, while CXCR1 and CXCR2 expressions in neutrophils were reduced by exposing peripheral blood to the GMA-carrier. Conclusions: GMA may regulate the immune system in patients with an immune-mediated disorder by inducing a biological response of neutrophils with a PICD-like reaction.

https://pubmed.ncbi.nlm.nih.gov/33395614/

Xiuli Chen, Lian Lou, Haiying Tang, Xiaoyan Tan, Jian Bi, Hao Wu, Na Li, Yingde Wang, Jingwei Mao, 18 February 2021 https://doi.org/10.1002/jca.21887

Active UC is associated with gut microbiota dysbiosis. GMA therapy exerts a strong regulatory effect on the gut microbiota in patients with UC.

https://onlinelibrary.wiley.com/doi/10.1002/jca.21887?af=R

Masahiro Iizuka, Takeshi Etou , Yosuke Shimodaira , Takashi Hatakeyama , Shiho Sagara,World J Gastroenterol 2021 Mar 28;27(12):1194-1212. 

Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

https://pubmed.ncbi.nlm.nih.gov/33828394/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006096/pdf/WJG-27-1194.pdf

Szabolcs Kiss, Dávid Németh, Péter Hegyi , Mária Földi , Zsolt Szakács, Bálint Erőss , Benedek Tinusz , Péter Jenő Hegyi, Patrícia Sarlós , Hussain Alizadeh, BMJ Open 2021 May 19;11(5):e042374.

The results support the hypothesis that patients with active UC have a better chance of clinical remission if GMA is administered as an adjunctive therapy. As regards the frequency of AEs, we found no statistically significant difference between the two groups. With regard to remission maintenance, GMA was identified as an effective alternative therapeutic option

https://pubmed.ncbi.nlm.nih.gov/34011580/

e042374.full.pdf (bmj.com)

Munenori Kawai, Chiharu Kawanami, Akihisa Fukuda & Hiroshi Seno

Clin J Gastroenterol. 2021 Oct;14(5):1561-1566. doi: 10.1007/s12328-021-01460-0. Epub 2021 Jun 8.

An 18-year-old woman was admitted to our hospital with fever, diarrhea and painful skin ulcers in both pretibial areas starting 19 days earlier. The skin lesions appeared deep necrotic ulcers with violaceous undermined borders. She had been diagnosed as ulcerative colitis and primary sclerosing cholangitis (PSC) 6 and 5 years before, respectively, and had stopped having regular check-up and refused medication for years. Her clinical history and skin lesions led us to suspect of pyoderma gangrenosum (PG). The skin biopsy showed aseptic abscess formation with neutrophils infiltration in the dermis without bacteria. Thus, she was diagnosed with PG. 1 mg/kg/day of prednisolone was administered and ten sessions of granulocyte and monocyte adsorption apheresis (GMA) were started. Magnetic resonance cholangiography showed multifocal bile duct strictures due to PSC. Total colonoscopy revealed ulcerative pancolitis with spared normal mucosa in the rectum. After the treatments, her symptoms and the skin lesion improved dramatically. She was discharged on the 45th day with 25 mg/day of prednisolone. In conclusion, this is the first reported case of PG with PSC-associated colitis that showed dramatic response to the concomitant GMA therapy with corticosteroids. Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

https://pubmed.ncbi.nlm.nih.gov/34101129/

Miho Hatanaka ¹, Kazuyasu Fujii ¹, Takuro Kanekura ¹ J Dermatol 2021 Aug;48(8):e376-e377. doi: 10.1111/1346-8138.15946. 

Pyoderma gangrenosum (PG), acne(A), and Suppurative hidradenitis (SH) syndrome (PASHs) is a recently proposed disease entity clinically characterized by PG, acne, and SH, belonging to the spectrum of hereditary autoinflammatory syndrome with PG. Although biologic agents targeting interleukin-1 and tumor necrosis factor-α have been recommended for the treatment of PASHs, their efficacy has not been well established because of its rarity.
Granulocyte and monocyte adsorption apheresis is an extracorporeal apheresis unit designed to selectively remove pathogenic granulocytes and macrophages that produce proinflammatory cytokines. The efficacy of GMA on PG has been reported, and treatment of PASHs with GMA has been described in a single case report

Successful treatment of pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome with granulocyte and monocyte adsorption apheresis – PubMed (nih.gov)