TARO OSADA＊, SUMIO WATANABE＊, Juntendo Medical Journal61 (6), 588-596

In recent years, landmark progress has been made in the treatment of patients with inflammatory bowel
diseases (IBD). The anti-tumour necrosis factor (TNF)-α antibody era has shown that mucosal healing is a key
therapeutic goal, and may predict the sustainability of remission or resection-free survival in IBD patients.
Further, the anti-TNF-α antibody infliximab (IFX) became an alternative medication for refractory UC in 2010
under the Japan national health reimbursement scheme. However, to induce remission in steroid-refractory UC,
currently several therapeutic options are available in Japan including cytapheresis, tacrolimus, and anti-TNF-α
biologics, but as yet, there are no guidelines for the sequence and timing of these therapeutic interventions.
Additionally, there are many patients who do not respond, or are intolerant, to anti-TNF-α biologics. Recently,
new strategies like faecal microbiota transplantation and anti-leucocyte infiltration have been tested for induction
and maintenance of remission in IBD patients. This paper provides an overview of the latest treatment options and
future perspectives in IBD therapy

https://www.jstage.jst.go.jp/article/jmj/61/6/61_588/_pdf/-char/en

Caroline Schultheiß ¹, René Weischenberg, Andrea Herrmann, Bernhard Haller, Roland M Schmid, Wolfgang Reindl, Wolfgang Huber, Artif Organs . 2015 Feb;39(2):187-92

Dose-intensified GMA as reported in this study provided an encouraging short-term response rate of 70% in patients with moderately to severely active UC not responding to standard steroid or immunomodulator therapy. Although all patients relapsed not later than 16 weeks, GMA might be useful to reduce steroid and immunomodulator usage, or to delay surgery in this patient group.

(nih.gov)https://pubmed.ncbi.nlm.nih.gov/24981894/

Tetsuro Takayama, Susumu Okamoto, Tadakazu Hisamatsu, Makoto Naganuma, Katsuyoshi Matsuoka, Shinta Mizuno Rieko Bessho, Toshifumi Hibi, Takanori Kanai, PLoS ONE 10(6): e013119

The aim of this study is to predict the need of operation after CAP therapy of UC patients on an individual level using artificial neural network system (ANN).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481415/pdf/pone.0131197.pdf

Selective myeloid leucocyte depletion was effective for remission induction and improving patients‘ quality of life. Baseline demographics such as disease activity level, duration and corticosteroid dependency appear to predict response to GMA. Additionally, patients with a first UC episode who were drug naive responded well to GMA and achieved a favorable long-term disease course by avoiding pharmacologics from an early stage of their inflammatory bowel disease. These findings should help to end unnecessary use of medical resources by targeting GMA to patients who may respond well.

Yoko Yokoyama ¹, Kenji Watanabe ², Hiroaki Ito ³, Masakazu Nishishita ⁴, Koji Sawada ⁵, Yusuke Okuyama ⁶, Kazuichi Okazaki ⁷, Hisao Fujii ⁸, Hiroshi Nakase ⁹, Tsutomu Masuda ¹⁰, Ken Fukunaga ¹¹, Akira Andoh ¹², Shiro Nakamura ¹³ ,

Cytotherapy 2015 May;17(5):680-8. 

https://pubmed.ncbi.nlm.nih.gov/25804800/

Rodolfo Sacco ¹, Tomotaka Tanaka, Takayuki Yamamoto, Giampaolo Bresci, Abbi R Saniabadi, Expert Rev Gastroenterol Hepatol. 2015 Mar;9(3):327-33.

The authors‘ view is that in patients with UC, there is an evolving scope for therapeutic opportunity based on taking away the sources of inflammatory cytokines, also considering the favorable safety profile of GMA.

https://pubmed.ncbi.nlm.nih.gov/25160857/

Tomotaka Tanaka and Abbi Saniabadi,

By the power of colonoscopy over a decade in patients with UC, we have learnt that all patients with the first UC episode and short duration of disease readily respond to GMA and can be spared from multiple drug therapy. Similarly, moststeroid naïve or dependent patients who have a fair level of intact mucosal tissue are potential responders to GMA. Additionally, it is important to bear in mind that patients who respond to GMA and avoid pharmacologics from the initial stages of their UC continue to respond well and attain a favourable future clinical course. Patients with extensive loss of the mucosal tissue together with
a long history of exposure to multiple pharmacologics are unlikely to respond to GMA. Further,GMA with the Adacolumn is very much favoured by patients for its safety profile. Serious side effects are very rare. This is in sharp contrast to multiple severe side effects associated with most conventional pharmacologics and new biologics. Our view is that in patients with UC, there is an evolving scope for therapeutic opportunity based on taking away the sources of inflammatorycytokines. However, selective depletion of activated and elevated myeloid lineage leucocytes to achieve IBD remission by applying GMA represents an intrigue, but this is yet to be achieved in all treated patients.

RII-15-01.pdf (smjournals.com)

T. Yamamoto, T. Tanaka, R. Sacco, doi:10.1111/apt.13021

https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.13031

Akiko Arimura ¹, Miho Hatanaka, Hiromi Katsue, Shigeto Matsushita, Takuro Kanekura, J Dermatol. 2015 Apr;42(4):438-9.

https://pubmed.ncbi.nlm.nih.gov/25655018/

Chiharu Tominaga ¹, Masaaki Yamamoto ¹, Yasutomo Imai ¹, Kiyofumi 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.

https://pubmed.ncbi.nlm.nih.gov/25848350/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357681/pdf/cde-0007-0029.pdf

Massimo Ghio, Giorgia Bodini, Paola Contini, Vincenzo Savarino, Edoardo Savarino Gastroenterology, 2015 148(4), S-698–. doi:10.1016/S0016-5085(15)32367-2 

Background Plasmapheresis is used in immune-mediate disease in order to remove humoral factors and, in addition, to modulate cellular immunity. It has been shown that during aphaeretic centrifugation , whole and/or re-folded soluble HLA class I molecules (sHLAI) bind to the circuit surfaces. Similarly, neutrophils can bind sHLA-I molecules with immunoglobulin-like transcript (ILT) membrane receptors, becoming hereafter sensitive to
the immunomodulation of sHLA-I such as transcriptional and post-transcriptional transforming growth factor (TGF)-β1 modulation. On the other hand, TGFβ signaling plays a major role in the pathogenesis of inflammatory bowel diseases and it is known to directly induce Foxp3 expression. Besides, Foxp3 expression has been reported increased in patients who responded to granulocytes apheresis with remission of clinical symptoms. Aim The aim of this prospective study was to evaluate a possible sHLA-I mediated immunomodulation in granulocytes and monocytes apheresis in ulcerative colitis patients who responded to therapy. Methods We prospectively enrolled a total of 10 patients (4M/6F; mean age 49, range 27-73) who achieved clinical remission with GMA. The GMA sessions (5 cycle/session) were performed using Adacolumn device. Instantly before each single apheresis and immediately after each procedure, neutrophils were analyzed for a possible in vivo aftermath of sHLA-I binding with corresponding ligands Ig-like-transcripts. The concentrations of sFasL molecules were determined by double-determinant immunoassay (DDIA) and the concentrations of TGFb1 were determined by double-determinant immunoassays utilizing a commercially available kits. Results Between every GMA cycle a significant upregulation of intracytoplasmic TGFβ1 molecule or TGFβ1-mRNA was observed in neutrophils and CD8+ T lymphocytes drawn along the apheretic therapeutic treatments. In particular, the greatest mean increase was found after the first and the forth GMA cycles (from +1% to +30%). A significant up-regulation of sFasL and TGFβ1 concentrations in plasma was observed along the procedures. Similarly, the mean difference increases in comparison with previous samples were constantly found raising during scheduled blood sampling for both molecules. In CD4+ T lymphocytes, unable to bind sHLA-I, the aphaeretic procedures never induced TGFβ1 modulation Conclusion: Our findings suggest that the immunosuppressive effects following therapeutic apheresis might at least in part depend on activated leukocyte sensitivity to sHLA-I molecule bioactivity.

https://www.gastrojournal.org/article/S0016-5085(15)32367-2/pdf