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Down-regulation of interferon-γ parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background & aims

Pilot studies have indicated a therapeutic role for an apheresis device (Adacolumn) that selectively adsorbs leukocytes in patients with inflammatory bowel diseases. It may also exert immunoregulatory effects contributing to its clinical efficacy. This study aimed to correlate the clinical response to leukocyte apheresis with the expression of key cytokines in mucosal tissue, in peripheral leukocytes, and in plasma.

Methods

Ten patients (seven with Crohn’s disease and three with ulcerative colitis, median age: 31 years) with mild to moderately chronic activity were recruited to an open study. Patients were refractory to or had a relapse despite conventional treatment including azathioprine. Leukocyte apheresis was performed once a week for five consecutive weeks. Clinical efficacy was assessed on week 7 and after 12 months. Colonoscopy with multiple biopsies was performed at the start of the study and after 7 weeks for semiquantitative immunohistochemical analyses of cytokines. Cytokine levels in blood and the proportion of cytokine producing CD4+ and CD8+ lymphocytes were determined.

Results

The apheresis procedures were well tolerated and no major adverse events were encountered. The median clinical activity score decreased from 12 to 7 on week 7 (P=0.031, n=9) and to 4 after 12 months (P=0.004, n=9). Five patients were in clinical remission at the 12th month. Tissue interferon (IFN)-γ-positive T-cells decreased in clinical responders (P=0.027) after apheresis. In parallel, significantly lower levels of IFN-γ-producing lymphocytes were detected in peripheral blood. IFN-γ-positive cells in pretreatment biopsies completely disappeared or decreased in posttreatment biopsies sampled on week 7 in responders (P=0.027) and appeared to predict the maintenance of long-term remission or response after 12 months.

Conclusions

Leukocyte apheresis is a novel and safe nonpharmacological adjunct therapy that may prove useful in steroid refractory or dependent patients when conventional drugs have failed. Down-regulation of IFN-γ in mucosal biopsies and in peripheral leukocytes may be a predictive marker for sustained, long-term response.

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Acknowledgements

This work was supported by an unrestricted grant from Terumo Europe NV, and by grants from the Swedish Research Council, the Karolinska Institutet and the Otsuka Frankfurt Research Institute. We thank T. Nieminen, E. Lindroos, and I. Arestrom for their skillful technical assistance.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, 17176, Sweden

    V. Muratov, J. Lundahl & K. Elvin

  2. Unit of Reumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    A. K. Ulfgren

  3. Unit of Gastroenterology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    R. Löfberg

  4. Dialysis Unit, HMQ Sophia Hospital, Stockholm, Sweden

    I. Fehrman

  5. Mabtech AB, Stockholm, Sweden

    N. Ahlborg

  6. Department of Clinical Pathology, MediLab AB, Täby, Sweden

    Å. Öst

  7. Otsuka Frankfurt Clinical Research Institute, Frankfurt, Germany

    N. Hittel

  8. JIMRO, Takasaki, Japan

    A. Saniabadi

  9. Inflammatory Bowel Diseases (IBD)-unit, Sophiahemmet, Stockholm, Sweden

    R. Löfberg

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  1. V. Muratov
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Correspondence to V. Muratov.

Additional information

An invited commentary on this paper is available at http://dx.doi.org/10.1007/s00384-005-0082-5

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Muratov, V., Lundahl, J., Ulfgren, A.K. et al. Down-regulation of interferon-γ parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study. Int J Colorectal Dis 21, 493–504 (2006). https://doi.org/10.1007/s00384-005-0069-2

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