C. Legendre

Eculizumab Improves Posttransplant Thrombotic Microangiopathy Due to Antiphospholipid Syndrome Recurrence but Fails to Prevent Chronic Vascular Changes

Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b‐9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b‐9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b‐9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.

AKT/mTORC pathway in antiphospholipid-related vasculopathy: a new player in the game

Since the early 1990s, it has become clear that the antiphospholipid syndrome (APS) is not only associated with vascular thrombosis but also with a severe intimal hyperplasia called ‘antiphospholipid arterial vasculopathy’. Such vasculopathy has been recognized as a major contributor to large artery occlusion rather than thrombosis or vasculitis. These lesions are described in many vascular territories, including the coronary, carotid or mesenteric arteries. However, their best morphological characterization was conducted in the kidneys, where these lesions have been called APS nephropathy (APSN). These lesions have been associated with a progressive decline of kidney function leading to end-stage renal failure. Interestingly, APSN recurs after kidney transplantation, sometimes quickly, and reduces the allograft survival rate. The molecular pathways that were involved in the development of such lesions were unknown, and therefore no specific treatment was offered to these patients.

Dramatic Improvement of Severe Cryptococcosis-Induced Immune Reconstitution Syndrome With Adalimumab in a Renal Transplant Recipient

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis‐associated IRIS 1 week after immunosuppression reduction. High‐dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor‐α (TNF‐α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.

Cyclosporine abrogates de novo generation of Tregs independently of IL-2.

Recent work by Kang et al. brings new insight into the mechanism by which cyclosporine A (CsA) blocks tolerance induction (1). Previous studies demonstrated that CsA inhibits activation induced cell death (AICD) in alloreactive T cells as well as expansion of the Foxp3-expressing regulatory T cells (Tregs). Given the crucial role of IL-2 in both AICD and homeostasis of Tregs, the authors hypothesize that the CsA-induced inhibition of tolerance is IL-2 dependent. Indeed, providing a long-lasting form of IL-2 (IL-2/Fc) reversed the effects of CsA. Combined IL-2/Fc and CsA enhanced AICD of alloreactive T cells and dramatically augmented the suppressive capacities of Tregs (1). Therefore, the authors propose that this may be a promising therapeutic combination in human transplantation.

The First Transplant Kidney Biopsy Ever Performed

This transplant was performed in emergency because the recipient’s congenitally single kidney had to be removed to keep under control a posttrauma hemorrhage. The transplanted kidney functioned well for the first 21 days, when suddenly he became anuric. For the first time in the history of transplantation, on January 17th, 1953, a surgical wedge biopsy of the transplant was performed a few hours after anuria had occurred. The reported changes were: ‘‘major interstitial plasma cell and lymphocytic infiltration, dilated vessels entirely filled with blood with ischemic glomerular capillaries and basement membrane thickening. In addition, there is severe tubular cell necrosis with no evidence of epithelial regeneration.’’

Clinical significance of T cell monitoring during antithymocyte globulin induction in renal transplantation.

T CELL monitoring during antithymocyte globulin (ATG) induction therapy has been reported by several investigators to reduce the total amount of the drug given, and therefore the number of complications and cost of treatment.1 We decided to carry out this investigation in order to compare the efficacy and the adverse events observed with different ATG regimes and to correlate the T cell subset monitoring with the different clinical events.