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Background: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. Methods: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. Results: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eß] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eß 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eß1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. Conclusions: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
RESUMO
AIM: To evaluate risk factors for primary sclerosing cholangitis (PSC) recurrence (rPSC) after orthotopic liver transplantation (OLT) in patients with well-preserved colons. METHODS: We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with follow-up of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen (HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods. RESULTS: Altogether, 31 men and 16 women with a median (range) age of 36 (15-68) years at the time of OLT and a median follow-up of 122 (60-249) mo were included. rPSC was confirmed in 21/47 (44.7%) of patients, a median 63 (12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio (HR): 4.02, 95% confidence interval (CI): 1.58-10.98] and history of acute cellular rejection (rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis (rPSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor (rPSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04 (rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03 (rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07 (rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles. CONCLUSION: De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.