Elevated sCD may indicate an increased immunological

Elevated sCD30 may indicate an increased immunological capacity to react against foreign HLA antigens. Due to contact with bioincompatible dialysis membranes and exposure to HLA or HLA-cross-reactive infectious agents (D\'Orsogna et al., 2011), end-stage renal disease patients exhibit alterations in their immune response, including increased numbers of interferon (INF)-γ-producing HLA-cross-reactive memory T-cells, reduced numbers of regulatory T-cells, augmented in vitro expansion of T-cells expressing CD30, and an increased serum sCD30 content (Susal et al., 2002; Velásquez et al., 2012). Our group reported that cytomegalovirus infection can lead to an increase of serum sCD30 levels in transplant patients (Weimer et al., 2006). Chan et al. identified CD30+ T-cells as the major INF-γ and IL-5 cytokine-producing human T-lymphocyte subset generated in response to stimulation with alloantigens (Chan et al., 2002). We showed previously that polyclonal and allogeneic stimulation results in upregulation of CD30 on memory T-cells and an INF-γ-dependent release of sCD30 from these myd88 pathway (Velasquez et al., 2013). Although a biological function of sCD30 has not been established in vivo, sCD30 has greater affinity for CD30-ligand in vitro as compared to CD30 and is potentially capable of blocking CD30, CD30-ligand interactions (Hargreaves and Al-Shamkhani, 2002), reducing the availability of CD30-ligand on lymphocytes or decreasing the ability of regulatory T-cells to inhibit graft-reactive T-cells (Tarkowski, 2003). Neutralization of IFN-γ resulted in abrogation of sCD30 release from memory T-cells in vitro (Velasquez et al., 2013). High production of IFN-γ by alloreactive anti-donor effector memory T-cells in patients awaiting kidney transplantation has been associated with early acute rejection of kidney transplants (Heeger et al., 1999). The presence of a low-level or declining memory T-cell response might serve as an explanation why, despite the presence of DSA, many patients possess low sCD30 levels. Routinely applied immunosuppression appears to be able to control such low-level T-cell-mediated antibody responses. In sCD30 and DSA positive patients, some 40% of transplanted kidneys failed within 3years. This rate is unacceptable. Allocation of HLA well-matched donor kidneys to these truly “high risk” patients may be an effective approach to minimize graft loss. It was shown in previous studies that deleterious sCD30 as well as HLA antibody effects can successfully be compensated by good HLA matching (Susal et al., 2003; Susal et al., 2009). Special desensitization and immunosuppression programs may be suitable alternatives. Because of the side effects associated with such treatment, many centers do not perform transplants from live donors if DSA are present. Our data suggest that transplantations can be safely performed in DSA positive patients if the pretransplant sCD30 level is low. However, before such policy can be generally implemented, further studies are required that confirm the present findings. In conclusion, our data indicate that the presence of pretransplant DSA is associated with a high rate of graft rejection only if patients concomitantly have high levels of pretransplant sCD30 which reflect a preactivated immune response. For practical purposes, ovulation appears that only patients positive for both DSA and sCD30 require special therapeutic and organizational measures, such as the elimination of DSA from the patient\'s circulation, potent immunosuppression, good HLA matching and intense posttransplant monitoring (Morath et al., 2010; Susal et al., 2003; Susal et al., 2009). According to this analysis, the majority of pretransplant DSA positive patients exhibit low sCD30 levels and can be expected to enjoy good graft survival without special provisions.
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Introduction