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Monoclonal versus Polyclonal Antibodies. Monoclonal antibodies are specific and bind a single antigen as shown on the left in the figure. Polyclonal antibodies are non-specific and bind multiple antigens as shown on the right in the figure.
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Kidney transplantation remains the most effective modality for the treatment of end-stage renal disease. The development of induction therapy has significantly reduced the incidence of acute rejection within the first six months following kidney transplantation. As a result, induction therapy is typically administered in the majority of kidney tran...
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Context 1
... therapy commonly refers to antibodies against specific or non-specific antigens on targeted immune cells (Table 1). These can be classified as lymphocyte depleting agents and non-lymphocyte depleting agents. The categorization is based on the ability of the therapeutic agent to target specific antigens or cells, leading to a decrease in the total cellular expression or reduction in cell counts. Most depleting agents are relatively potent with potential for toxicity with prolonged administration (i.e. OKT3). On the other hand, non- depleting agents are generally well-tolerated with reasonable side effect profiles, yet are less potent (i.e. anti-interleukin-2 receptor antibody). Depleting agents are also used for severe or refractory cases of acute rejection and have proven to be more effective than glucocorticoids in treating these episodes of acute rejection [9]. Polyclonal antibodies are typically heterogeneous, with batch-to-batch variability, variable in- vivo reactions, typically require larger doses, and are less susceptible to immune elimination (Figure 1). Monoclonal antibodies are more consistent, predictable, and require smaller doses. Murine monoclonal antibodies are susceptible to immune elimination, but chimeric (e.g. basiliximab) and especially humanized (e.g. alemtuzumab, daclizumab) antibodies are less susceptible to immune elimination. Some major institutions have modified their immunosuppression regimen to avoid long-term steroid maintenance. These regimens have utilized more potent induction agents (i.e. rabbit Antithymocyte globulin [rATG]) even in higher risk patients, such as the elderly or patients with multiple co-morbidities. The armamentarium of induction agents in modern transplantation has expanded, leading to the clinical dilemma in selecting the most appropriate agent for a given patient while taking into account co-morbidities, donor quality, immunological status, and planned maintenance ...
Similar publications
To evaluate the efficacy and safety of antibody induction therapies in kidney transplantation. Systematic literature searches were undertaken using MEDLINE, Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled trials (RCTs) comparing three antibody induction therapies (alemtuzumab, interleukin-2 receptor antibodies and ant...
Citations
... Ribeiro et al [20] in a study from Brazil found that the major infectious cause of the hospitalized renal transplant patients is CMV which accounted for 16.1%. There is evidence that over immunosuppression has been linked to both CMV infection and also malignancies [21]. Both HBV as well as HCV can be found among renal transplants and cause a higher frequency of complications including membranous nephropathy in renal transplant patients [22,23]. ...
... 12 Induction therapy helps prevention of acute rejection particularly in the first year. 13 Variations exist in the protocols of using induction therapy in India. Two major induction agents used include anti-thymocyte globulin and basiliximab. ...
BACKGROUND
Increasing deceased donor kidney donation is the only answer to fill the large gap between availability and need for organ
donors. Deceased donor kidney transplant rates are picking up in the Southern and Western regions of India and there is a
need to look at the outcomes at various institutes and share the experience.
The objective of the study is to evaluate outcomes of deceased donor kidney transplants (DKT) done at a tertiary care
centre in Mumbai.
MATERIALS AND METHODS
In this retrospective study, outcomes of all DKTs done from April 2012 to July 2017 were evaluated. Induction
immunosuppression consisted of two to three doses of anti-thymocyte globulin (1.5 mg/kg per dose) and methylprednisolone
pulses whereas maintenance immunosuppression regimen consisted of prednisolone, mycophenolate mofetil and tacrolimus.
The data was analysed for demographic profile of recipients and donors, comorbidities in recipients, cause of kidney disease in
recipients, waiting period on dialysis, delayed graft function, episodes of rejections, induction agents used, maintenance
immunosuppressants, infection episodes, patient and graft survival and causes of death.
RESULTS
A total of 21 DKTs (52.4% male recipients) were performed during the study period. The mean (+ SD) age of recipients and
donors was 46.71 (±10.6) and 47.8 (+13.5) years respectively. Incidence of biopsy proven acute cellular rejection was 9.5%.
Patient survival at one, three and five years were 90.5%, 84.5% and 84.5% respectively. Four (19.04%) grafts were lost during
the study period, three grafts were lost because of death of the patients (two at three months and one at 22 months posttransplant) and only one other graft was lost at 43 months with patient returning to dialysis. Three patients (14.3%) died during
the study period; two due to sepsis and one due to cardiovascular disease.
CONCLUSION
Current study results suggest that DKT can be successfully carried out with good results even with the current limitations.
... | DISCUSSIONSeveral clinical studies have examined whether induction therapy, with various dosing (ranging from 4.2 to 10.5 mg/kg total) of thymoglobulin, would be safe and effective in kidney transplantation. Among these studies, there were varying degrees of success with episodes of acute rejection ranging from 3.6% to 19%, and some with significant side effects including high infection rates.18,19,20 Yet, the optimal dosage and regimen are still not well established, as excessive impairment of the cell-mediated immunity may increase the risk of opportunistic infections and post-transplant malignancies. ...
... In 2014, the most commonly used induction therapies in kidney transplantation were rabbit antithymocyte globulin (rATG) (approximately 50%), basiliximab (approximately 20%), and alemtuzumab (approximately 15%). 4,20,21 rATG is a poly-clonal T cell-depleting antibody manufactured in rabbits. 20 Alemtuzumab is a humanized mAb that depletes B and T cells by targeting the CD-52 glycoprotein cell surfaces. ...
... 4,20,21 rATG is a poly-clonal T cell-depleting antibody manufactured in rabbits. 20 Alemtuzumab is a humanized mAb that depletes B and T cells by targeting the CD-52 glycoprotein cell surfaces. 22 Some proponents of alemtuzumab endorsed the idea that this therapy could facilitate steroid-free transplants. ...
... 22 Some proponents of alemtuzumab endorsed the idea that this therapy could facilitate steroid-free transplants. 20,23,24 Basiliximab is a nondepleting mAb that prevents T cell activation by blocking the IL-2 receptor on cell surfaces. A randomized trial suggests basiliximab is associated with fewer infections overall than rATG, but is less effective at preventing acute allograft rejection. ...
Kidney transplant recipients often receive antibody induction. Previous studies of induction therapy were often limited by short follow-up and/or absence of information about complications. After linking Organ Procurement and Transplantation Network data with Medicare claims, we compared outcomes between three induction therapies for kidney recipients. Using novel matching techniques developed on the basis of 15 clinical and demographic characteristics, we generated 1:1 pairs of alemtuzumab-rabbit antithymocyte globulin (rATG) (5330 pairs) and basiliximab-rATG (9378 pairs) recipients. We used paired Cox regression to analyze the primary outcomes of death and death or allograft failure. Secondary outcomes included death or sepsis, death or lymphoma, death or melanoma, and healthcare resource utilization within 1 year. Compared with rATG recipients, alemtuzumab recipients had higher risk of death (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.03 to 1.26; P<0.01) and death or allograft failure (HR, 1.18; 95% CI, 1.09 to 1.28; P<0.001). Results for death as well as death or allograft failure were generally consistent among elderly and nonelderly subgroups and among pairs receiving oral prednisone. Compared with rATG recipients, basiliximab recipients had higher risk of death (HR, 1.08; 95% CI, 1.01 to 1.16; P=0.03) and death or lymphoma (HR, 1.12; 95% CI, 1.01 to 1.23; P=0.03), although these differences were not confirmed in subgroup analyses. One-year resource utilization was slightly lower among alemtuzumab recipients than among rATG recipients, but did not differ between basiliximab and rATG recipients. This observational evidence indicates that, compared with alemtuzumab and basiliximab, rATG associates with lower risk of adverse outcomes, including mortality.
... Immunosuppressive agents used for induction therapy in renal transplantation are antibodies that either target specific antigens on the surfaces of recipient's T cells or act non-specifically on the recipient's immune cells. They are classified into lymphocyte depleting or lymphocyte non-depleting agents depending on the ability of the medications to target specific antigens on cell surfaces leading to a decrease in the cellular expression of the antigens or cause non-specific immunological destruction of the recipient's lymphocytes resulting in a reduction of their number [23]. ...
... Alemtuzumab (Campath) is another depleting agent currently in use. It is an Immunoglobulin G class 1 (IgG1) humanized monoclonal antibody to rat anti-human CD52 [23]. ...
... Thymoglobulin is a depleting polyclonal heterologous antibody that binds to multiple T cell receptors and antigens that are involved in adhesion, antigen recognition and co-stimulation. Its depleting effect takes place within 24hrs of administration with a long half-life [23]. ...
In organ transplantation, a wide variety of injurious events such as ischaemia-reperfusion injury, endothelial damage and the traumatic exposure of tissues during surgery occur intra-operatively. The barrage of multiple antigens presented to the recipient cause very intense immunological reaction to occur at the time of transplantation. Thus, an induction immunosuppressive protocol aimed at maximal immunosuppression in the peri-operative period when immunological stimulation is maximal is justified. Organ transplant recipients of African descent are generally considered as high immunological-risk patients in view of the intense immunological response to transplanted organs seen in these patients compared with their Caucasian counterparts. However, due to the huge additional cost of induction antibody medications, most centers in resource-poor economies in Africa base their induction protocol on high doses of calcineurin based triple-drug therapy. Outcomes from the centers have been considerably poorer in terms of allograft rejection, graft loss and patient survival, compared with other parts of the world where high-risk patients received antibody induction therapy. Basiliximab induction protocols may offer cost–benefit advantages in resource constrained centers compared with currently used calcineurin based triple-drug therapy. The clinical and financial benefits of reduced acute allograft rejection rates, graft loss and the excellent side effect profile Basiliximab in renal transplant recipients, potentially outweighs the additional costs incurred in the management of higher acute rejection rates, and graft loss in calcineurin based triple-drug therapy. This reflective review article, examines the possible role of Basiliximab induction protocol as a means of improving clinical outcomes of renal transplantation, in African transplant centres operating in financial constraint economies.
... However, the benefits are minimized by unchanged graft and patient survival rates. 10 Our study showed that the incidence of biopsy-confirmed acute rejection and delay graft function was significantly higher in patients in the ATG group compared with those in the alemtuzumab group. Our results also showed that there was lower incidence of leuko-penia in the ATG-treated group compared with alemtuzumab group (Table 2). ...
We retrospectively compared induction therapy utilizing alemtuzumab and antithymoglobulin (ATG) in high-risk kidney transplant recipients in our center. Two hundred and fifty-one patients underwent kidney transplantation between 2009 and 2012. The high-risk patients were defined as those who had two or more times kidney transplantation and/or more than 30% panel reactive antibody. We studied 130 high-risk kidney transplant candidate; 58 (44.6%) patients received induction immunosuppressive therapy with alemtuzumab, and 72 (55.4%) with ATG. Delayed graft function developed in 11 patients receiving alemtuzumab, against the 27 patients who receiving ATG (P = 0.021). Acute cellular rejection episodes were observed in five patients in the alemtuzumab group and 19 patients in the ATG group (P = 0.009). There were three graft failures in the alemtuzumab group and eight graft failures in the ATG group due to rejection episodes. We found immunosuppressive induction therapy with alemtuzumab a significantly less incidence of acute rejection and delayed graft function than induction therapy with ATG in the high-risk kidney transplant recipients.
