Cytokine secretion in mixed lymphocyte culture: a prognostic indicator of renal allograft rejection in addition to HLA mismatching

We have previously demonstrated significant inter-individual variations in cytokine protein secretion between normal individuals and patients prior to renal transplantation. In this study, pre-transplant patient vs. donor mixed lymphocyte cultures (MLC) were set up between 57 renal allograft patient...

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Bibliographic Details
Published in:Transplant immunology 2000-06, Vol.8 (2), p.109-114
Main Authors: Cartwright, N.H, Demaine, A.G, Hurlock, N.J, McGonigle, R.J, Rowe, P.A, Shaw, J.F, Szydlo, R.M, Kaminski, E.R
Format: Article
Language:English
Subjects:
Cytokines
Cytokines - secretion
Female
Graft Rejection
histocompatibility antigen HLA
Histocompatibility Testing
Humans
Interferon-gamma - secretion
Interleukin-10 - secretion
Interleukin-6 - secretion
Kidney Transplantation - immunology
Lymphocyte Culture Test, Mixed
Mixed lymphocyte culture (MLC)
Mixed lymphocyte reaction (MLR)
Multivariate Analysis
Prognosis
Rejection
Renal transplantation
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Summary:We have previously demonstrated significant inter-individual variations in cytokine protein secretion between normal individuals and patients prior to renal transplantation. In this study, pre-transplant patient vs. donor mixed lymphocyte cultures (MLC) were set up between 57 renal allograft patient/donor pairs, and secretion of cytokine protein (IL-2, IL-4, IL-6, IL-10 and IFN-γ) into the culture supernatant measured by ELISA. Significant inter-individual variations in protein secretion in MLC were observed for all cytokines studied. Univariate analysis demonstrated that high levels of IFN-γ and IL-10 in MLC and spontaneous IL-4, together with female donor sex and a high degree of HLA mismatching (especially HLA-DR) were significantly associated with rejection. However, multivariate analysis revealed the greatest risk of rejection (RR=25.5, P=0.003) was associated with a combination of high IL-10 secretion in MLC and mismatching for at least four HLA antigens (HLA-A, -B and -DR). It remains to be determined whether cytokine secretion in MLC is linked to cytokine gene polymorphisms. In future, assays for measuring either cytokine secretion or genetic polymorphisms may prove to be useful in aiding donor selection and tailoring immunosuppressive therapy.
ISSN:0966-3274
1878-5492
DOI:10.1016/S0966-3274(00)00015-0