Akerele, O.F.; (2006) Ocular monitoring in immunosuppressed patients and quantification of immunosuppression by assessment of intracellular cytokines. Doctoral thesis , University of London.

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Abstract

Although laboratory indices, such as drug levels, are in routine use for monitoring immunosuppression, these do not always correlate well with an individual's risk of toxicity. In practice individual organs are monitored for toxicity with a combination of laboratory and clinical methods. These methods are limited by the fact that one has to await compromise before making therapeutic changes and there are often idiosyncrasies in the way individuals respond. Ocular complications can be sight threatening and many have proposed routine ocular monitoring in immunosuppressed patients. This study prospectively monitored a cohort of patients receiving high levels of immunosuppression for the prevention of rejection of heart, lung and heart-lung transplants for the development of ocular complications and to assess ocular morbidity. Specific surrogate markers that gave more information about the level of immunosuppression in a particular patient would improve patient care. Cytokines have the advantage of being directly generated by the immune response and offer promise as surrogate markers. Various, and not always consistent, cytokine profiles have been described for a number of conditions. Flow cytometry with intracellular cytokine staining allows quantification of the amount of cytokine present. These studies used this technique to describe the cytokine profile and changes in cytokine profile seen in patients during treatment for autoimmune uveitis and in patients with human immunodeficiency virus (HIV) receiving combination anti-retroviral therapy (ART). These studies emphasized the importance of prompt and careful clinical examination in the presence of clinical symptoms but did not support routine screening of patients on high levels of immunosuppression. Accurate measurements of interleukin-2 (IL-2) and interferon-gamma (IFNgamma) in patients with uveitis did not correlate well with disease activity. In contrast patients with different HIV profiles did show measurably different Thl cytokine expression providing information on the T cell deficits that persist despite treatment with ART.

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