A multiplex bead array analysis to monitor donor-specific cytokine responses after withdrawal of immunosuppression in HLA-identical living related kidney transplant patients.
ABSTRACT Immune reactivity after HLA-identical living related (LR) kidney transplantation can be caused by minor histocompatibility antigen and non-HLA antigen mismatches between donor and recipient. In our center, HLA-identical LR kidney transplant recipients receive azathioprine (AZA) or mycophenolate mofetil (MMF) in combination with corticosteroids for 1 year after transplantation. Thereafter, AZA or MMF was withdrawn, and the patients were treated with steroid monotherapy as maintenance therapy. We questioned whether withdrawal of AZA or MMF affected the donor-specific lymphocyte proliferation and cytokine production. Donor and third-party T-cell reactivities were determined by mixed lymphocyte reactions and by cytokine production using multiplex bead array technique. The donor and third-party proliferative capacities were not affected after withdrawal of AZA or MMF. Thirteen of 17 cytokines were detected by the multiplex bead array technique. No differences were observed after third-party induced cytokine production after withdrawal of AZA or MMF. However, production of donor-specific interferon-gamma and macrophage inflammatory protein-1beta increased after discontinuation of AZA or MMF, but no clinically relevant acute rejection was observed. In conclusion, after HLA-identical LR kidney transplantation, donor-specific cytokine responses can be found when AZA or MMF therapy is discontinued. The clinical relevance of this phenomenon is still not evident.
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ABSTRACT: Disparities in minor histocompatibility antigens between HLA-matched organ and bone marrow donors and recipients create a potential risk for graft failure and graft-versus-host disease. These conditions necessitate lifelong pharmacological immunosuppression of organ and bone marrow transplant recipients. Recent technical advances have resulted in the identification of the chemical nature of the first human minor histocompatibility antigens. A new era of research has begun to provide insights into the genetics of minor antigens and their putative role in transplantation.Current Opinion in Immunology 03/1996; 8(1):75-81. · 8.77 Impact Factor
- Transplantation 01/2000; 70(9):1549-1554. · 3.78 Impact Factor
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ABSTRACT: Cytokines play a pivotal role in the regulation of immunologic, hematologic and wound-healing processes. They function to stimulate as well as inhibit the proliferation, differentiation and maturation of a variety of cell types. Thus, their functions are pleiotropic as well as interdependent to the extent that any cytokine may have effects that are synergistic or antagonistic with other cytokines. Cytokines also display redundancy when one mimics the functions of others. These characteristics imply that measuring the levels of one cytokine in a biologic system provides only a fraction of the information that is relevant to the existing physiologic state. A more realistic indication of the complexity of cellular interactions would include measurements of multiple cytokines at any time point. One method of multiplexed analysis can be performed by capture of the cytokines on an array of fluorescent microspheres for quantitation by flow cytometry. This technology has been applied to a variety of biomolecules, but simultaneous quantitation of multiple cytokines in a small sample volume has become rapid, inexpensive, reliable and informative.Journal of Immunological Methods 09/2003; 279(1-2):277-85. · 2.23 Impact Factor