Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine, which is thought to play a major role in the pathogenesis of inflammatory diseases, including allergy. TNF is produced at the early stage of allergen sensitization, and then continues to promote the inflammation cascade in the effector phase of allergic reactions. Consequently, anti-TNF treatment has been proposed as a potential therapeutic option. However, recent studies reveal anti-intuitive effects of TNF in the activation and proliferative expansion of immunosuppressive Tregs, tolerogenic DCs and MDSCs. This immunosuppressive effect of TNF is mediated by TNFR2, which is preferentially expressed by immunosuppressive cells. These findings redefine the role of TNF in allergic reaction, and suggest that targeting TNF-TNFR2 interaction itself may represent a novel strategy in the treatment of allergy.
The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV+ donor to CMV+ recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk.