Ziwei Huang ¹, Vikram Singh Raghuwanshi ¹, Gil Garnier ¹Front Bioeng Biotechnol. 2017 Jul 17:5:41. doi: 10.3389/fbioe.2017.00041

The functionality and aging mechanism of antibodies physisorbed onto cellulosic films was investigated. Blood grouping antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) were adsorbed onto smooth cellulose acetate (CAF) and regenerated cellulose (RCF) films. Cellulose films and adsorbed IgG layers were characterized at the air and liquid interface by X-ray and neutron reflectivity (NR), respectively. Cellulose film 208 Å thick (in air) swell to 386 Å once equilibrated in water. IgG adsorbs from solution onto cellulose as a partial layer 62 Å thick. IgG and IgM antibodies were adsorbed onto cellulose and cellulose acetate films, air dried, and aged at room temperature for periods up to 20 days. Antibody functionality and surface hydrophobicity were measured everyday with the size of red blood cell (RBC) agglutinates (using RBC specific to IgG/IgM) and the water droplet contact angle, respectively. The functionality of the aged IgG/IgM decreases faster if physisorbed on cellulose than on cellulose acetate and correlates to surface hydrophobicity. IgG physisorbed on RCF or CAF age better and remain functional longer than physisorbed IgM. We found a correlation between antibody stability and hydrogen bond formation ability of the system, evaluated from antibody carbonyl concentration and cellulosic surface hydroxyl concentration. Antibody physisorbs on cellulose by weak dipole forces and hydrogen bonds. Strong hydrogen bonding contributes to the physisorption of antibody on cellulose into a non-functional configuration in which the molecule relaxes by rotation of hydophobic groups toward the air interface.

Functionality of Immunoglobulin G and Immunoglobulin M Antibody Physisorbed on Cellulosic Films – PubMed (nih.gov)

Functionality of Immunoglobulin G and Immunoglobulin M Antibody Physisorbed on Cellulosic Films – PMC (nih.gov)

Chie Kurihara Toshihide Ohmori Shingo Kato Koji Yakabi Satoshi Mochida Soichiro Miura Gastroenterology 2017 152 (5) Suppl. S764

Background: The number of the elderly patients of ulcerative colitis (UC) is growing as the population ages. Because elderly patients with UC sometimes become refractory to treatment, it is important to select an appropriate induction therapy for elderly patients at the early phase of UC disease. To predict which therapy is effective before treatment will be useful for the decision of later therapeutic strategy. Granulocyte and monocyte adsorptive apheresis (GMA) that was developed for selective depletion of activated granulocytes and monocytes/
macrophages from peripheral blood is non-pharmacological therapy for inflammatory bowel disease. It is beneficial than the other therapy in the point that it has fewer side effects. GMA is effective and safe as induction therapy in UC, and commonly used in Asia and north Europe. GMA is one of hopeful candidate of elderly therapy. We investigated the relationship between therapeutic efficacy of GMA and age, and examined whether mRNA expressions of cytokines and chemokines in colonic mucosa showed presence of age-related change. Methods: Thirty-two active UC patients, mean age 36.7 years, range 14-70 years, were enrolled in this study. All patients received 10 or 11 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Assessment of disease activity and colonic mucosal healing were determined based on Mayo score. In this study, elderly patients were defined as those >55 years of age. mRNA expressions of cytokines and chemokines were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: There were no significant differences in sex, duration of disease, location of disease, CRP, WBC and Mayo score before the first GMA treatment between elderly group and non-elderly group. After the last GMA session, the ratios of mucosal healing in elderly group and non-elderly group were 2 of 6 (33.3%) and 16 of 26 (61.5%), respectively. In all patients, before treatment of GMA, mucosal healing group showed significantly higher mRNA expression of inflammatory cytokines and chemokines such as MIP-1β, TNFα, IL1β and IL8 in colonic mucosal tissue than that of non-mucosal healing group (P <0.05). In particular, in elderly group, the degree of mRNA expression of MIP-1β and IL23 in colonic mucosa before GMA treatment was higher in mucosal healing group than in non-mucosal healing group (P <0.05). High expressions of MIP-1β and IL23 showed sensitivity, specificity, positive predictive value and negative predictive value of 100% as a marker of mucosal healing after GMA in elderly group. Conclusion: Mucosal IL23 and MIP-1β mRNA expression before treatment in elderly were significantly higher in responder than non-responder to GMA treatment. We propose that measuring of expression of these molecules is useful to expect therapeutic efficacy of GMA in elderly patients with UC.

https://www.gastrojournal.org/action/doSearch?text1=mo1730&field1=AllField

Cabriada, J.L., Rodríguez-Lago, I.

Enfermedad Inflamatoria Intestinal 20017 (16) 2, 62-69 DOI: 10.1016/j.eii.2016.12.001 

Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.

https://www.elsevier.es/es-revista-enfermedad-inflamatoria-intestinal-al-dia-220-articulo-granulocitoaferesis-2017-puesta-al-dia-S1696780116300999

Masanao Sakanoue ¹, Yuko Higashi ¹, Takuro 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/

Zhenfei Liu ¹, Xueliang Jiang ², Chengcheng Sun ³ ,Eur J Intern Med. 2016 Dec;36:e26-e27.

https://pubmed.ncbi.nlm.nih.gov/27614377/

Keiji Shimazu ¹, Takumi Fukuchi ², Insung Kim ³, Yuki Noguchi ³, Megumi Iwata ¹, Shintaro Koyama ^2 4, Satoshi Ubukata ², Atsuo Tanaka ¹ , Ther Apher Dial 2016 Aug;20(4):383-9.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/27523079/

Yoshioka, Shinichiro; Mitsuyama, Keiichi; Kuwaki, Kotaro; Yamauchi, Ryosuke; Yamasaki, Hiroshi; Fukunaga, Shuhei; Takedatsu, Hidetoshi; Tsuruta, Osamu; Torimura, Takuji (2016). Tu1987 A Longitudinal Study of FDG-PET in Crohn’s Disease Patients Receiving Granulocyte/Monocyte Apheresis Therapy. Gastroenterology, 2016 150(4), S998–. doi:10.1016/s0016-5085(16)33380-7 

Background: Endoscopy is the gold standard for the diagnosis and follow-up of patients with Crohn’s disease (CD). However, a less invasive approach is now being sought for the management of these patients. The objective of this study was to examine whether 18Ffluorodeoxyglucose (FDG)-positron emission tomography (PET) might be relevant for monitoring the disease activity in CD patients undergoing granulocyte/monocyte apheresis (GMA). Methods: This study was conducted in 12 patients with CD, who were receiving treatment with 10, once a week GMA sessions with the Adacolumn. The response to treatment was monitored by measuring the standard laboratory variables, the Crohn’s disease activity index (CDAI) score, the international organization for the study of inflammatory bowel diseases (IOIBD) score, and the regional and global bowel uptakes on FDG-PET. Results: In 6 of the 12 patients, significant improvement of the CDAI was observed after the final session of GMA. The patients who showed clinical response to GMA had a decrease in the regional and global bowel uptakes on FDG-PET, whereas those who did not respond showed no change. In the patients who responded to the GMA, the decrease in regional bowel uptake on FDG-PET in each disease area of the same patient varied in parallel. There was a significant correlation between decrease in the global bowel uptake on FDG-PET and improvement of
the CDAI and IOIBD scores. Conclusion: The longitudinal changes in FDG-PET uptakes are of potential clinical interest for assessing the regional and global bowel disease activity in CD patients undergoing GMA therapy.

https://www.gastrojournal.org/article/S0016-5085(16)33380-7/pdf

Masashi Ohno ¹, Shigeki Koyama, Mariko Ohara, Kazumi Shimamoto, Yu Kobayashi, Fumiyasu Nakamura, Kazuki Mitsuru, Akira Andoh

Intern Med.  2016;55(1):25-30. doi: 10.2169/internalmedicine.55.5422. Epub 2016 Jan 1.

A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

https://pubmed.ncbi.nlm.nih.gov/26726081/

https://www.jstage.jst.go.jp/article/internalmedicine/55/1/55_55.5422/_article

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/

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