Alemtuzumab Induction and Antibody-Mediated Kidney Rejection After Simultaneous Pancreas-Kidney Transplantation

Pascual, Julio; Pirsch, John D.; Odorico, Jon S.; Torrealba, José; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen; Knechtle, Stuart J.; Sollinger, Hans W.; Samaniego‐Picota, Milagros

doi:10.1097/tp.0b013e31818c6db0

Cited by 48 publications

(35 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As we mentioned previously, patients receiving alemtuzumab induction showed higher incidence of antibody-mediated rejection [67,69,124,125]. Their acute rejection rate was not increased compared to the control group, but rather the humoral component was increased in patients with acute rejection in this patients group.…”

Section: B Cells In Animal Model Of Chronic Rejectionmentioning

confidence: 51%

The role of B cells in solid organ transplantation

Kwun

Bulut

Kim

et al. 2012

Seminars in Immunology

Self Cite

View full text Add to dashboard Cite

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

show abstract

Section: B Cells In Animal Model Of Chronic Rejectionmentioning

confidence: 51%

The role of B cells in solid organ transplantation

Kwun

Bulut

Kim

et al. 2012

Seminars in Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a single-center retrospective analysis, induction therapy with alemtuzumab versus no induction resulted in similar 12-month survival but greater freedom from rejection, despite lower calcineurin levels and a steroid-free regimen [46]. However, reports of a higher incidence of humoral rejection in renal transplantation following lymphocyte depletion with alemtuzumab have raised concerns with regard to its utility as an induction agent in sensitized patients [47,48].…”

Section: Induction Therapymentioning

confidence: 95%

Approach to the Sensitized Patient Awaiting Heart Transplantation

Patel¹,

Kobashigawa²

2014

Curr Transpl Rep

View full text Add to dashboard Cite

The management of the sensitized patient awaiting heart transplant remains a challenge and an active area of research. The development of solid-phase immunoassays (including the C1q assay) has allowed high-resolution determination of antibodies most likely to be associated with antibody-mediated rejection and adverse outcomes. The precision of these techniques has permitted the adoption of the virtual crossmatch, substantially expanding the donor pool for sensitized patients and reducing wait times to transplant. Desensitization strategies continue to evolve, and the most effective therapies appear to be a combined approach utilizing antibody depletion, targeted B cell or plasma cell therapy, or immunomodulation. Further therapy in addition to cytolytic induction may be required at transplant, with judicious monitoring post-transplant for antibody rebound and rejection.

show abstract

“…Important side effects include autoimmune thyroiditis, hemolytic and uremic syndrome (HUS) [162,163] and unusual infections [164,165]. Recent data suggested a persistent higher incidence of ABMR in RTR [163,166], a high recurrence rate of auto-immune glomerulopathies in Alemtuzumab induced kidney/pancreas transplant recipients under a tacrolimus/mycophenolate-based regimen [167], and a poorer kidney graft survival due to increased infectious complications [165].…”

Section: Anti-cd52 (Alemtuzumab)mentioning

confidence: 99%

Advances in pharmacotherapy to treat kidney transplant rejection

Bamoulid

Staeck

Halleck

et al. 2015

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Despite a lack of randomized trials, early acute T-cell-mediated rejection can be treated effectively in most cases without graft loss. The necessity to treat SCR is currently unclear. Due to a lack of effective therapies, new treatment approaches for antibody-mediated rejection are an urgent medical need to improve long-term outcomes. Future research should aim to better define pathophysiology and histology, stratify risk, and develop rational treatment strategies from randomized controlled trials, in order to establish the value of novel therapies in the arsenal of rejection pharmacotherapy. However, the effective prevention of rejection with minimal side effects still remains the goal in immunosuppression.

show abstract

Alemtuzumab Induction and Antibody-Mediated Kidney Rejection After Simultaneous Pancreas-Kidney Transplantation

Cited by 48 publications

References 25 publications

The role of B cells in solid organ transplantation

The role of B cells in solid organ transplantation

Approach to the Sensitized Patient Awaiting Heart Transplantation

Advances in pharmacotherapy to treat kidney transplant rejection

Contact Info

Product

Resources

About