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Rheumatology Advance Access originally published online on July 13, 2004
Rheumatology 2004 43(10):1275-1282; doi:10.1093/rheumatology/keh311
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Rheumatology Vol. 43 No. 10 © British Society for Rheumatology 2004; all rights reserved

Paper

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

M. Treusch*, R. Vonthein1, M. Baur, I. Günaydin, S. Koch, N. Stübiger2, A. K. Eckstein3, H.-H. Peter4, T. Ness5, M. Zierhut2 and I. Kötter*

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

Correspondence to: I. Kötter, Department of Internal Medicine II (Hematology/Oncology/Immunology/Rheumatology), University Hospital, Otfried-Müller Strasse 10, D-72076 Tübingen, Germany. E-mail: ina.koetter{at}med.uni-tuebingen.de

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.

KEY WORDS: IFN-{alpha}, Behçet's disease, Lymphocyte subpopulations

*The first and last author have contributed equally to this work.


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