Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: an adjunct or an alternative to drug therapy?
Inflammatory and/or autoimmune diseases like ulcerative colitis (UC) or Crohn's disease (CD) are debilitating chronic disorders that poorly respond to pharmacological interventions. Further, drug therapy has adverse effects that add to disease complications. The current thinking is that disorders like inflammatory bowel disease (IBD) reflect an over exuberant immune activation driven by cytokines including TNF-alpha. Major sources of cytokines include myeloid leukocytes (granulocytes, monocytes/macrophages), which in IBD are elevated with activation behavior and are found in vast numbers within the inflamed intestinal mucosa. Accordingly, myeloid cells should be the targets of therapy. Adacolumn is filled with cellulose acetate beads that selectively adsorb and deplete myeloid cells and a small fraction of lymphocytes (FcgammaR and complement receptors bearing cells). In one study, 20 steroid naive patients with moderate (n = 14) or severe (n = 6) UC according to Rachmilewitz despite 1.5-2.25 g/day of 5-aminosalicylic acid received 6 to 10 Adacolumn sessions at 2 sessions/week. Efficacy was assessed 1 week after the last session. The majority of patients responded to 6 sessions, 17 (85%) achieved remission. In 2 of the 3 non-responders, CAI was 8 and 12 in 1; all 3 had deep colonic ulcers at study initiation. Decreases were seen in total leukocytes (P = 0.003), % neutrophils (P = 0.003), % monocytes (P = 0.004), an increase in lymphocytes (P = 0.001), decreases in C-reactive protein (P = 0.0002), and rises in blood levels of soluble TNF-alpha receptors I (P = 0.0007), II (P = 0.0045). In a separate study, a case with very severe steroid refractory UC who received up to 11 sessions responded well and avoided colectomy. Further, myeloid cell purging with Adacolumn has been associated with the release of IL-1 receptor antagonist, suppression of TNF-alpha, IL-1beta, IL-6, IL-8, down-modulation of L-selectin and the chemokine receptor CXCR3. In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.
Saniabadi
Abbi R
AR
Japan Immunoresearch Laboratories, Nishiyokote Machi, Takasaki, Japan. saniabadi@jimro.co.jp
Hanai
Hiroyuki
H
Suzuki
Yasuo
Y
Ohmori
Toshihide
T
Sawada
Koji
K
Yoshimura
Naoki
N
Saito
Yasushi
Y
Takeda
Yuji
Y
Umemura
Kazuo
K
Kondo
Kazunao
K
Ikeda
Yasuhiko
Y
Fukunaga
Ken
K
Nakashima
Mitsuyoshi
M
Beretta
Alberto
A
Bjarnason
Ingvar
I
Lofberg
Robert
R
D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000529:Complementary Therapies / Q000379:methods; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007937:Leukapheresis / Q000379:methods; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D010586:Phagocytes / Q000276:immunology* / Q000648:ultrastructure
D016207:Cytokines