Immunosuppressive treatment of organ transplant recipients is associated with an increase in the occurrence of human papillomavirus (HPV) related anogenital (pre)malignancies. This cohort study investigated the genotype-specific prevalence of HPV infections in a large cohort of female renal transplant recipients (RTRs). Participants self-collected a cervicovaginal sample for detection and genotyping of HPV. Besides, they completed a questionnaire regarding sociodemographic variables, medical data and sexual behavior. Anogenital screening was offered to all HPVpositive participants. A total number of 218 female RTRs was included. The prevalence of mucosal HPV infections was 27.1% and 17.4% for high risk HPV in particular. The studied cohort showed a broad range of HPV genotypes and multiple HPV genotypes were found in 27.1% of HPV-positive patients. Seven participants were identified with occult premalignant anogenital lesions. In conclusion, this study shows a high point-prevalence of HPV in female RTRs (agematched West-European general population: 9-10%) with a shift in the distribution of genotypes as compared with the general population. Moreover, a substantial number of patients with occult premalignancies was identified. The introduction of selfsampling for HPV positivity can help in early detection of (pre)malignant anogenital lesions in this vulnerable population.Abbreviations: HPV, human papillomavirus; hrHPV, high risk human papillomavirus; lrHPV, low risk human papillomavirus; RR, relative risk; RTRs, renal transplant recipients
Human leukocyte antigen (HLA)-DP is considered a target for humoral immune response in clinical transplantation. This study analyses the incidence of HLA-DP antibodies in renal patients. Development and epitope specificity of donor-specific antibodies (DSA) and non-DSA (NDSA) were examined. Pre- and posttransplant sera of 338 patients were screened for HLA-DP antibodies using the luminex single antigen assay. Positive patients, partners and/or kidney donors were HLA-DP typed by sequence-specific oligonucleotides. Potential epitopes were mapped by comparing the amino acid sequences of HLA-DP hypervariable regions (HVR) A-F of recipient, partner and/or donor. Specificities in the sera were aligned to deduce the HVR motif responsible for the antibodies. HLA-DP antibodies were detected in 14% of the patients (48/338). Before transplantation, the antibodies were shown in 23% (10 females and 1 male) and 77% were found after transplantation (30 in patients after the first, 7 after the second graft). Specificities were never restricted to individual mismatched antigens; broad HLA-DP sensitization was found as a rule. A single HVR mismatch was present in 80% of the DSA and in 79% of the NDSA. No HLA-DPA specific antibodies were found. Our findings confirm that HLA-DP antibodies are specific for epitopes shared by different HLA-DP antigens, indicating that only a restricted number of mismatched epitopes are recognized by the recipients immune system. Matching for immunogenic HLA-DP epitopes for renal transplantation seems to be functionally more relevant than classical matching at the allelic level.
The clinical significance of the presence of donor-specific anti-human leucocyte antigen (HLA) antibodies (DSA) prior to renal transplantation detected solely by solid-phase techniques remains unclear. This study was designed to determine the clinical relevance of the recently introduced bead-based Luminex donor-specific crossmatch (LumXm). A group of 165 patients transplanted between 1997 and 2001 were tested. Of 165 recipients transplanted with a negative complement-dependent cytotoxicity crossmatch, 32 proved to have a positive Luminex crossmatch. Sixteen were positive for class I, 15 were positive for class II, 1 was both class I and II positive and 133 recipients were negative. Acute rejection (AR)-free survival for all recipients was 77%, and there was no difference in AR-free survival between LumXm-positive and LumXm-negative recipients. Overall graft survival after a median follow-up time of 8 years was 56%. Recipients with a positive class I LumXm had worse long-term graft survival (P = 0.006). In recipients with a positive class I LumXm, 5-year graft survival was 41% vs 70% in negative patients and 10-year graft survival was 27% vs 56%. Positivity for class II LumXm was not a significant risk factor for graft failure (P = 0.7). In conclusion, pretransplant DSA detected by the LumXm had no impact on AR episodes. Class II LumXm positivity proved no significant risk factor for graft failure, but the value of the class II LumXm is questionable. A positive class I LumXm resulted in worse long-term graft survival compared with a negative one.
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