ABSTRACT
Background: Prolonged (val)ganciclovir [(V)GCV] exposure for ≥6 weeks is a known predisposing factor for cytomegalovirus (CMV) drug resistance. However, the selection of this threshold was based on limited data. In this study, we sought to reappraise the risk factors for the development of (V)GCV resistance through a specific focus on kidney transplant recipients (KTRs). Methods: This single-center retrospective study included 313 consecutive KTRs treated for a first CMV episode. Adjusted Cox multivariate regression analysis was used for identifying independent risk factors. Results: Antiviral drug resistance was identified in 20 (6%) KTRs. A cumulative (V)GCV exposure for more than 6 weeks (regardless of the viral load) was not associated with antiviral drug resistance (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 0.33-18.30, P = .38). In contrast, persistent CMV DNAemia requiring (V)GCV treatment for more than 8 weeks was the main independent risk factor for antiviral drug resistance (HR = 11.68, 95% CI = 2.62-52.01, P = .001). The (V)GCV treatment for more than 8 weeks was given to 9% and 18% of patients who had persistent or recurrent CMV DNAemia, respectively. These scenarios were associated with the occurrence of drug resistance in 39% and 12% of cases, respectively. Conclusions: Cumulative (V)GCV exposure ≥6 weeks regardless of the viral load is not associated with antiviral drug resistance. In contrast, prolonged exposure to (V)GCV during CMV replication (with a cutoff ³8 weeks) seems to be a key factor.
ABSTRACT
HLA antibody detection with single antigen flow beads (SAFB) assays is impaired by complement interference whose frequency, predictability and distribution among HLA antigens have not been analyzed in large cohorts. We compared in two patients' cohorts the routine follow-up SAFB profiles obtained in class I (n = 129) and class II (n = 85) with and without ethylenediaminetetraacetic acid (EDTA)-treatment. The presence of complement interference was defined according to the reproducibility of the SAFB assays evaluated with our class I and II routine positive control sera. Interference occurred in 29.5% and 45.9% of patients in class I and II, respectively. In the untreated condition, at serum level, neither the number of positive beads, the highest bead mean fluorescence intensity (MFI) nor MFI at bead level, satisfactorily predicted interference. HLA-C were the least affected among class I beads. HLA-DQ beads were the most affected in class II. At least one antibody specificity was falsely negative without EDTA for about 3% of sera in class I and 9% in class II. EDTA-treatment did not significantly modify the low-MFI strengths (500-3000 range). This study emphasizes the high frequency of complement interference and the importance and advantages of systematically pretreating sera with EDTA before performing SAFB assays.
Subject(s)
Complement System Proteins/metabolism , Flow Cytometry/methods , Cohort Studies , Edetic Acid , Follow-Up Studies , HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Testing , Humans , Isoantibodies/blood , Microspheres , Prevalence , Reproducibility of ResultsABSTRACT
HLA-A*24:391 differs from HLA-A*24:02:01:01 by one nucleotide substitution at position 33.
Subject(s)
Alleles , HLA-A Antigens/genetics , Histocompatibility Testing/methods , Base Sequence , Exons/genetics , HumansABSTRACT
HLA-C*16:116 differs from HLA-C*16:01:01:01 by single-nucleotide substitution at position 30.
Subject(s)
Alleles , HLA-C Antigens/genetics , Histocompatibility Testing/methods , Sequence Analysis, DNA , Base Sequence , Exons/genetics , Humans , Sequence AlignmentABSTRACT
HLA-B*07:305 differs from HLA-B*07:02:01:01 by one nucleotide substitution at position 255.
