Immunologic monitoring in solid organ transplantation

Improvement of patient and graft survival rates and the post transplantation quality of life depends on many pre- and post-transplant factors, such as tissue compatibility, immunosuppressive therapy, as well as the early detection and treatment of both acute and chronic graft rejection. Allograft antigens presented to the host immune system in association with the major histocompatibility complex (MHC)-encoded molecules initiate lymphocyte activation and proliferation of the primed lymphocytes leading to both cellular and/or humoral rejection. The cytokines are essential for the differentiation, proliferation, and amplification of the T-cell responses (Schwartz, 1992). The most important one is interleukin-2 (IL-2), which is essential for activated T-cell proliferation. Monitoring intragraft cytokines such as IL-2, IL-4, IL-10 and interferon-y using real-time PCR (Flohe et al., 1998; Hahn et al., 2001), although invasive, is simple and has been shown to be effective in characterizing and predicting graft rejection and tolerance. Koop et al, (2004) showed that differentiation between chronic rejection and chronic cyclosporine toxicity in renal transplant patients may be more reliably detected using the molecular technique of a real-time PCR quantitative analysis of the renal cortical mRNA levels of laminin p2 and extracellular matrix regulation molecule transforming growth factor-p. Using a less invasive technique to monitor intracellular T-cell cytokines such as (Il-2, IL-4,IL-10, TNF, RANTES, and IFNy) levels in lymphocyte subsets (CD3/CD4 and CD3/CD8) as well as activation markers CD25 (IL-2R), CD40 CD69, CD71, CD103 and cytotoxic effector molecules such as perforin, granzyme B and FasL in peripheral blood and urine cytokines was shown to be predictive (Li et al., 2001; Ding et al., 2003; Muthukumar et al., 2003; Dadhania et al., 2003; Tatapudi et al., 2004; Shoker et al., 2000; Satterwhite et al., 2003; Sabek et al., 2002). Simon et al. (2003) reported that renal rejection diagnosis using perforin and granzyme B gene expression measurements was possible 2-30 days before traditional clinical diagnosis (i.e. elevation of serum creatinine) and that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Findings from these studies suggest that serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy. Such early intervention may be more effective than therapy initiated after organ damage has already occurred.

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