Solid-organ transplant recipients receiving immunosuppressive therapy appear to have a poor response to Covid-19 vaccination. A group of 101 consecutive transplant recipients received two doses of ...the BNT162b2 vaccine 1 month apart and a third dose 2 months after the second dose; 40% had antibodies after the second dose and 68% had antibodies after the third dose.
Antibodies against PD1 have been used to treat progressive multifocal leukoencephalopathy (PML), a rare brain disease caused by JC virus. We used these antibodies (nivolumab) to treat PML in 3 kidney ...transplant recipients. All died within 8 weeks of diagnosis. Hence, nivolumab did not improve PML outcome after solid organ transplantation.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A weak humoral response to two-doses of SARS-CoV-2 vaccine was observed in solid organ transplant (SOT) patients. Preliminary reports suggested the usefulness of a boost with a third dose. Herein, we ...report the humoral response in 396 SOT patients (mean age 59 ± 15 years, 65% men) who were given three doses messenger RNA-based vaccine (BNT162b2 vaccine Pfizer-BioNTech) (Table S1). Of these, 101 were included in our previous report.3 The two first doses were given one month apart, and the third dose was administered 59 (IQR25-75: 47–67) days after the second dose, that is, once the third dose was recommended by the French National Authority for Health. Anti-SARS-CoV-2 spike protein total antibodies were assessed the day of vaccination before the injection using either the Wantai enzyme-linked immunosorbent assay test (Beijing Wantai Biological Pharmacy Enterprise) (228 patients, 57.6%), or another anti-SARS-CoV-2 spike protein assay (n = 168) (Table S2). According to French law (loi Jardé), anonymous retrospective studies do not require institutional review board approval.
Abstract In contrast to other types of organ transplantation, liver-transplant recipients used to be considered highly resistant to donor-specific antibodies (DSAs). Consequently, most transplant ...programs did not consider the presence of DSAs at transplantation or during the follow-up. However, since the early 1990s, antibody-mediated pathological lesions have been recognized in ABO-incompatible liver-transplant recipients. Recent data confirm the detrimental effect of preformed and de novo DSAs in ABO-compatible liver transplantation, with inferior clinical outcomes in patients presenting with circulating antibodies. Acute antibody-mediated rejection (AMR), plasma-cell hepatitis, biliary stricture, but also long-term complications, such as chronic rejection, liver ductopenia, and graft fibrosis, are now recognized to be associated with DSAs. Moreover, some non-HLA DSAs are suspected to induce graft dysfunction. Clinical, biological, and histological patterns within AMR need to be clarified. Treatment of these complications has yet to be defined. This article summarizes recent advances concerning the impact of preformed and de novo DSAs in liver transplantation, it defines the complications associated with DSAs, and discusses the potential strategies to manage patients with such complications.
BACKGROUNDIt is widely accepted that HLA donor-specific antibodies (DSA) are associated with antibody-mediated rejection and graft loss. However, in many transplant programs, preformed anti–HLA-Cw ...and anti–HLA-DP DSA are not considered in organ allocation policies because their clinical relevance is still uncertain.
METHODSWe analyzed the clinical impact of Cw/DP DSA through a retrospective study, comparing 48 patients transplanted with isolated preformed Cw/DP DSA (Cw/DP DSA group) with (i) 104 matched HLA-sensitized kidney transplant recipients with No DSA at D0 (No DSA group) and (ii) 47 kidney transplant recipients with preformed A, −B, −DR, −DQ DSA (A/B/DR/DQ DSA group).
RESULTSA positive flow cytometry crossmatch in the Cw/DP DSA group was more frequent than in the No DSA group and as frequent as in the A/B/DR/DQDSA group. Two years after transplantation, the biopsy-proven acute rejection-free survival was worse in the Cw/DP and A/B/DR/DQ DSA groups than in the No DSA group (65%, 84%, 93%, P = 0.001 and P = 0.05, respectively). Accordingly, graft survival was lower in the Cw/DP and the A/B/DR/DQ DSA groups than in the No DSA group (87%, 89%, 95%, P = 0.02 and P = 0.1, respectively).
CONCLUSIONSThese results suggest that preformed anti–HLA-Cw and anti–HLA-DP DSA are as deleterious as anti–HLA A/B/DR/DQ DSA. It justifies their inclusion in kidney allocation programs and in immunological risk stratification algorithms.
To investigate the role of tacrolimus intra-patient variability (IPV) in adult liver-transplant recipients.
We retrospectively assessed tacrolimus variability in a cohort of liver-transplant ...recipients and analyzed its effect on the occurrence of graft rejection and
donor-specific antibodies (
DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil (with or without steroids) were included.
Twenty-two patients (18.5%) experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% OR = 3.07 95%CI (1.14-8.24),
= 0.03 or > 40% OR = 4.16 (1.38-12.50),
= 0.01), and a tacrolimus trough level of < 5 ng/mL OR=3.68 (1.3-10.4),
=0.014. Thirteen patients (11.2%) developed at least one
DSA during the follow-up. Tacrolimus IPV coded as a continuous variable: OR = 1.1, 95%CI (1.0-1.12),
= 0.006 of > 35% OR = 4.83, 95%CI (1.39-16.72),
= 0.01 and > 40% OR = 9.73, 95%CI (2.65-35.76),
= 0.001 were identified as predictors to detect
DSAs. IPV did not impact on patient- or graft-survival rates during the follow-up.
Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a
DSA after liver transplantation.
Hepatitis E virus genotype 3 (HEV3) and 4 (HEV4) can progress to chronic hepatitis in immunosuppressed patients.1 Ribavirin therapy has been shown to be efficient for treating chronic HEV infection ...in solid-organ-transplant recipients.2,3 Eighty percent of patients achieved a sustained virological response 24 weeks (SVR24) after ribavirin cessation.3 However, the optimal duration of ribavirin therapy is still undetermined. A rapid decrease of HEV RNA in blood under therapy was associated with SVR24.4 It has also been suggested that the presence of HEV polymerase mutations, such as the 1634R mutant, could influence the response to ribavirin therapy.5,6 We previouslyshowed that persistence of HEV RNA in the feces at the end of ribavirin therapy in patients with undetectable HEV RNA in blood was also associated with a higher risk of HEV infection relapse.7 This prompted us to prolong the duration of ribavirin therapy in patients who had undetectable HEV RNA in the serum but persistent detectable HEV RNA in the stools at the end of the scheduled duration. Herein, we retrospectively compared the SVR24 in solid-organ-transplant recipients for whom ribavirin treatment was prolonged when HEV RNA was still detectable only in the stools, to the SVR24 in a historical group of patients in whom ribavirin was systematically stopped at theend of the scheduled duration.
BACKGROUNDRibavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of ...immunosuppressant regimens on viral replication are unknownthus, determining the aim of our study.
METHODSThirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation.
RESULTSA sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin.
CONCLUSIONAn early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.
Abstract
Background
Patients with chronic kidney disease, dialysis patients and kidney transplant patients are at high risk of developing severe coronavirus disease 2019 (COVID-19). Data regarding ...the immunogenicity of anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (anti-SARS-CoV-2 mRNA) vaccines in dialysis patients were published recently. We assessed the immunogenicity of anti-SARS-CoV-2 mRNA vaccine in dialysis patients.
Patients and methods
One hundred and nine patients on haemodialysis (n = 85) or peritoneal dialysis (n = 24) have received two injections of 30-μg doses of BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) that were administered intramuscularly 28 days apart. Those who were still seronegative after the second dose were given a third dose 1 month later. Anti-SARS-CoV-2 antibodies were tested before and after vaccination.
Results
Ninety-one out of the 102 patients who had at least a 1-month follow-up after the second (n = 97) or the third (n = 5) vaccine doses had anti-SARS-CoV-2 antibodies. The seroconversion rate was 88.7% (86 out of 97 patients) among SARS-CoV-2 seronegative patients at the initiation of vaccination. Receiving immunosuppressive therapy was an independent predictive factor for non-response to vaccination.
Conclusion
Due to high immunogenicity and safety of mRNA vaccines, we strongly recommend prioritizing a two-dose vaccination of dialysis patients. A third dose can be required in non-responders to two doses. When possible, patients waiting for a kidney transplantation should be offered the vaccine before transplantation.
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