Leukocyte Apheresis in the Management of Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disease that affects the colon and rectum. Its pathogenesis is probably multifactorial including the influx of certain cytokines into the colonic mucosa, causing disease activity and relapse. The hypothesis of removing such cytokines from the circulation by leukocytapheresis was implemented to reduce disease activity, maintain remission, and prevent relapse. Many recent reports not only in Japan, but also in the West, have highlighted its beneficial effects in both adult and pediatric patients. Large placebo-controlled studies are needed to confirm the available data in this regard. In this article, we shed some light on the use of leukocyte apheresis in the management of autoimmune diseases, especially ulcerative colitis.     

The art of separation and adsorption: Historical review of apheresis in Japan

Apheresis therapy was first introduced into Japan from the United State as plasmapheresis by a centrifuge method. However, the invention of hollow fiber has subsequently lead to a membrane plasma separation. Selective removal of the plasma or cell component has been improved and matured in clinical application. Therapeutic apheresis has progressed and diversified with the development of technology for membrane separation by hollow fiber and adsorption with a physicochemical adsorbent in Japan.     

Selective adsorption of human CD4 T cells

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.     

Critical Care by Cytapheresis

Abstract: We report our experience of cytapheresis using a nonwoven polyester fiber filter to treat critical states of immune diseases. In 7 critical states of ulcerative colitis (UC), cytapheresis was effective in improving symptoms of UC. Administration of steroids was important in some cases. In 3 cases of renal transplantation, cytapheresis was also effective in controlling rejection. IgA nephropathy of transplanted cases was well controlled. Furthermore, an original disease such as focal segmental glomerulosclerosis (FCGS) in a transplant patient was well treated by extracorporeal immune modulation of the cytapheresis.     

Cytapheresis for the Treatment of Myeloperoxidase Antineutrophil Cytoplasmic Antibody‐Associated Vasculitis: Report of Five Cases

Abstract: To minimize the adverse effects of high‐dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO‐ANCA‐associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 ± 0.15 mg/kg/day (mean ± SD) (range 0.18–0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 ± 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low‐dose or intermediate‐dose PSL regimen, is effective in the treatment of ANCA‐associated vasculitis.     

Effects of cytapheresis on tumor necrosis factor receptor and on expression of CD63 in myeloperoxidase--antineutrophil cytoplasmic autoantibody-associated vasculitis

To evaluate the therapeutic potential of cytapheresis in myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis, plasma levels of soluble tumor necrosis factor receptors (sTNFR1, sTNFR2) and the expression of TNFR1, TNFR2, and CD63 on granulocytes were measured. The levels of sTNFR1 and sTNFR2, and the expression of TNFR1 and TNFR2 were significantly higher in MPO-ANCA-associated vasculitis patients than in normal controls. The levels of sTNFR1 and sTNFR2 increased significantly after cytapheresis (P < 0.001). The expression of TNFR1 showed a tendency to decrease after cytapheresis (P = 0.0535). The expression of CD63 decreased significantly after cytapheresis (P < 0.05). Because sTNFR1 and sTNFR2 act as TNF-antagonists, the increases of sTNFR1 and sTNFR2 after cytapheresis might contribute to inhibit the action of TNF-alpha. The decreased expression of TNFR1, which mediates the signal for polymorphonuclear cell respiratory burst, might also contribute to the reduction of inflammation. From these results, the inhibition of TNF action and removal of degranulated granulocytes appear to be related to the mechanism whereby cytapheresis can exert a beneficial and therapeutic function in the treatment of MPO-ANCA-associated vasculitis.     

脱细胞猪肺动脉带瓣管道的支架材料研究

目的研究心血管组织在经过适当脱细胞处理后的组织结构和生物学特性。方法对带瓣猪肺动脉管道进行脱细胞处理，所得组织和作为对照的新鲜天然组织分别进行HE染色、ETVG染色、免疫组化染色及扫描电镜检查，并测定各种大分子物质的含量；在小鼠皮下移植6周后测定组织钙含量及钙定位染色。结果脱细胞后的组织内未见细胞结构，基质结构基本保持。胶原和弹性蛋白含量增加。脱细胞后的组织在小鼠皮下移植后钙含量较天然组织明显下降。结论经过合适的脱细胞处理后，可以去除几乎所有的细胞成分，基本保留的基质结构，能显著减轻在异种移植时引起的钙化。     

Treatment with cytapheresis for antineutrophil cytoplasmic antibody-associated renal vasculitis and its effect on anti-inflammatory factors

To evaluate the efficacy of cytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) caused by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis, the renal prognosis and the mortality rate at 1 year after treatment were compared between a Cytapheresis Group and a Steroid Pulse Group. The Cytapheresis Group included 10 patients who were treated with cytapheresis and oral corticosteroids. Five had granulocytapheresis with the Adacolumn (Japan Immuno Research Laboratories Co. Ltd, Takasaki, Japan) and the remaining five had leukocytapheresis with the leukocyte removal filter, Cellsorba (Asahi Medical Co. Ltd, Tokyo, Japan). The Steroid Pulse Group was comprised of 12 patients who were treated with methylprednisolone pulse therapy and oral corticosteroids. In the Cytapheresis Group, renal function recovered in 70% of the patients and the mortality rate was 10%. In the Steroid Pulse Group, renal function recovered in 66.7% and the mortality rate was 33.3%, with infection as the cause of death. Total doses of corticosteroids converted to prednisolone dose during a 1 month period, ranged from 280 mg to 1226 mg in the Cytapheresis Group. On the other hand, these dosages ranged from 2375 mg to 8380 mg in the Steroid Pulse Group. These results indicated that the mortality rate by infection could be reduced by adding cytapheresis therapy. Concerning the mechanism of cytapheresis, anti-inflammatory factors such as soluble tumor necrosis factor receptor, and interleukin-10 reduced after cytapheresis. These changes might be responsible for the efficacy of cytapheresis. In conclusion, cytapheresis is thought to be one of the effective treatments for RPGN caused by MPO-ANCA-associated vasculitis, reducing the levels of anti-inflammatory factors.