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Rheumatology Advance Access published online on July 13, 2004
Rheumatology, doi:10.1093/rheumatology/keh311
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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Received November 17, 2003
Accepted June 15, 2004

Original Papers

Influence of human recombinant interferon-{alpha}2a (rhIFN-{alpha}2a) on altered lymphocyte subpopulations and monocytes in Behçet's disease

M. Treusch 1, R. Vonthein 2, M. Baur 1, I. Günaydin 1, S. Koch 1, N. Stübiger 3, A. K. Eckstein 4, H.-H. Peter 5, T. Ness 6, M. Zierhut 3, I. Kötter 1*

1 Department of Internal Medicine II (Hematology, Oncology, Immunology and Rheumatology), University Hospital, Tübingen, Germany
2 Department of Medical Biometry, University Hospital, Tübingen, Germany
3 Department of Ophthalmology, University Hospital, Tübingen, Germany
4 Department of Ophthalmology, University Hospital, Essen,Germany
5 Department of Internal Medicine, Division of Clinical Immunology and Rheumatology, University Hospital, Freiburg, Germany
6 Department of Ophthalmology, University Hospital, Freiburg, Germany

* To whom correspondence should be addressed. E-mail: ina.koetter{at}med.uni-tuebingen.de.


  Abstract

Objective. In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-{alpha}2a (IFN-{alpha}2a) (response rate 92%), although this is counterintuitive because IFN-{alpha} is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-{alpha} might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-{alpha}2a treatment.

Methods. Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-{alpha} treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry.

Results. Compared with the controls there is a significant elevation of monocytes (CD14+), CD8+/{gamma}{delta} T cells, CD3+/{gamma}{delta} T cells, natural killer (NK) cells (CD56+/CD16+) and activated/regulatory T cells (CD4+/CD25+ and CD8+/CD25+) in patients with active BD before treatment with IFN-{alpha}2a. Numbers of naïve T cells (CD8+/CD45+RA+/RO-, CD4+/CD45+RA+/RO-) were significantly lower. Under therapy, NK cells, CD8+/{gamma}{delta} T cells and CD3+/{gamma}{delta} T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients.

Conclusion. These results implicate the participation of NK cells and {gamma}{delta} T cells, especially CD8+/{gamma}{delta} T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-{alpha}2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-{alpha}2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.

Keywords: IFN-{alpha}; Behçet's disease; Lymphocyte subpopulations.

The first and last authors have contributed equally to this work.


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