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

H H Olsen ¹, V Muratov, K Cederlund, J Lundahl, A Eklund, J Grunewald, Clin Exp Immunol. 2014 Sep;177(3):712-9.

Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137856/pdf/cei0177-0712.pdf

https://pubmed.ncbi.nlm.nih.gov/24773420/

K Kamikozuru ¹, K Fukunaga, S Hirota, N Hida, Y Ohda, K Yoshida, Y Yokoyama, K Tozawa, K Kawa, M Iimuro, K Nagase, A R Saniabadi, S Nakamura, H Miwa, T Matsumoto Clin Exp Immunol 2009 May;156(2):320-7. doi: 10.1111/j.1365-2249.2009.03904.x. Epub 2009 Mar 9.

Regulatory T cells (T(reg)) have an essential role in maintaining immune tolerance in the gut. The functional CD4(+) T(reg) express the transcription factor forkhead box protein 3 (FoxP3) or a CD25(high) in humans. Further, depletion of elevated granulocytes/monocytes by extracorporeal adsorption (GMA) induces immunomodulation in patients with ulcerative colitis (UC). We investigated the impact of GMA on T(reg). Thirty-one UC patients, clinical activity index (CAI) 12.1 +/- 2.97, refractory to conventional medications including intravenous corticosteroid and 13 healthy controls (HC), were included. Patients received five GMA sessions over 5 weeks. Biopsies from the rectal mucosa and blood samples at baseline and post-GMA were immunostained with anti-CD4/FoxP3 and anti-CD4/CD25 antibodies for immunohistochemistry and flow cytometry. Following GMA, 22 of 31 patients achieved remission (CAI <or= 4, P < 0.01) and their endoscopic activity index decreased from 10.6 +/- 2.32 to 4.75 +/- 1.48 (P = 0.003). The circulating CD4(+)CD25(high+) T(reg) level was low and increased markedly in responders (P < 0.02). In the nine non-responders, the baseline CD4(+)CD25(high+) T(reg) level was about 50% of the level in the responders (P < 0.03) or in the HC (P < 0.01), and all nine had to undergo colectomy. Conversely, the number of CD4(+)/FoxP3(+) mucosal T(reg) in GMA responders decreased significantly after the fifth GMA session compared with the baseline level (P < 0.05). It is believed that the CD4(+) T(reg) has an essential role in the control of immune pathology in UC patients and a net influx of these cells from the circulation into the mucosa may proceed to suppress inflammation. GMA can impact the circulating as well as the mucosal levels of T(reg).

https://pubmed.ncbi.nlm.nih.gov/19292766/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759481/

Emilio Cuadrado ¹, Marta Alonso, Maria-Dolores de Juan, Pilar Echaniz, Juan-Ignacio Arenas, World J Gastroenterol. 2008 Mar 14;14(10):1521-7.

The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.

https://pubmed.ncbi.nlm.nih.gov/18330941/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693745/pdf/WJG-14-1521.pdf

Abbi R.Saniabadi, HiroyukiHanai, KenFukunaga, KojiSawada, ChikakoShima, IngvarBjarnason, RobertLofberg, https://doi.org/10.1016/j.transci.2007.08.003

The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD. GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14⁺CD16⁺ monocytes and was followed by an increase in CD4⁺ T lymphocytes including the regulatory CD4⁺CD25^high+Foxp3 phenotype. Hence, GMA could be a non-pharmacologic therapy for IBD with potential to spare steroids and other unsafe pharmacologic preparations.

https://www.sciencedirect.com/science/article/abs/pii/S1473050207001164