Association between female sex, IL28B genotype, but also DQB1*0301 allele and the outcome of acute hepatitis C virus infection

International audienceWe thank Grebely et al.1 for their recent InC study confirming that the IL28B genotype and female sex are associated with the spontaneous clearance of hepatitis C virus (HCV). However, we and others showed that spontaneous HCV resolution is associated with another genetic factor more than 10 years ago. This factor is the DQB1*0301 allele of the major histocompatibility complex class II.2 The IL28B genotype was shown to be the most important factor associated with a sustained virologic response to pegylated-interferon ribavirin therapy3 and also with the spontaneous outcome of HCV infection.4 However, the study4 showing that genetic variations in IL28B is associated with spontaneous clearance of HCV focused on a single nucleotide polymorphism and was not a genome-wide association study (GWAS). A new multicenter collaborative study5 on 919 North American and European subjects whose HCV was resolved spontaneously was conducted to explain the conflicting results.2, 4 It was shown5 that IL28B rs12979860 and DQB1*0301 rs4272729 alleles were independently associated with the spontaneous resolution of HCV. Surprisingly, these results are not discussed by Grebely et al

Successful retransplantation of a kidney allograft affected by thrombotic microangiopathy into a second transplant recipient.

International audienceThe donor organ shortage has compelled transplant centers to use organs from nontraditional sources. One example is the reuse of a previously transplanted organ, such as a kidney or liver retrieved from a brain-dead allograft recipient. For the first time, we reused a previously transplanted kidney that experienced intractable recurrent thrombotic microangiopathy (TMA) from a living allograft recipient. Within a few weeks posttransplantation, a deceased kidney allograft recipient developed intractable severe recurrent idiopathic TMA in the allograft despite intensive plasma exchanges and steroid and rituximab therapy. This required nephrectomy to cure TMA. The index recipient was believed to have a well-functioning allograft despite TMA (serum creatinine, 1.36 mg/dL [120 micromol/L]) and microalbuminuria with albumin of 1.2 g/dL [12 g/L]), and it appeared mildly damaged on biopsy examination. After donor and recipient informed consents were obtained and after approval of the French Agency of Biomedicine, the TMA allograft was reused and transplanted into a recipient whose original kidney disease was polycystic kidney disease. The retransplantation was uneventful, and at 6 months posttransplantation, the ultimate recipient's serum creatinine level was 1.06 mg/L (97 micromol/L) and albuminuria was 0.5 g/dL (5 g/L). A routine kidney biopsy showed mild glomerular lesions. After allograft nephrectomy, the donor's hematologic TMA symptoms dissipated within 10 days. We conclude that a kidney allograft with TMA recurrence can be successfully retransplanted into another recipient with excellent kidney function while still curing the first recipient of recurrent TMA. This might increase the number of kidney allografts from extended criteria donors

Définition et standardisation des bilans d’histocompatibilité en fonction du parcours du patient et du type de donneur : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC) et de la Société Francophone d’Histocompatibilité et Immunogénétique (SFHI)

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Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

Acute humoral rejection (AHR) is uncommon after ABO-compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Liver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy

Anti-Human Leukocyte Antigen Immunization After Early Allograft Nephrectomy

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HLA-DRB3/4/5 mismatches are associated with increased risk of acute GVHD in 10/10 matched unrelated donor hematopoietic cell transplantation

International audienceMatching for HLA‐A, ‐B, ‐C, and ‐DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA‐DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA‐DRB3/4/5 loci may help to lower transplant‐related morbidity and mortality. We therefore investigated the impact of HLA‐DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High‐resolution typing was performed at HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DPB1, and ‐DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5‐matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II‐IV acute graft‐versus‐host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft‐versus‐host disease‐free and relapse‐free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT