RESUMO
Human leukocyte antigen antibodies (HLA Abs) are associated with poor renal graft outcome. We selected 134 first kidney transplant recipients without HLA Ab (LABScreen® Luminex) before transplantation despite previous allogeneic exposure whether through blood transfusion (BT) and/or pregnancy (PR). We screened these patients for HLA Ab post-transplantation (yearly) and determined the risk of HLA Ab and donor-specific antibody (DSA) appearance according to BT/PR in a univariate and a multivariate model. Among the 134 patients (43 males/91 females), 56 were BT+/PR-, 41 BT-/PR+ and 37 BT+/PR+. Median delay between last PR or BT and transplantation were 25.9 years (0.5-47.8) and 8 months (0.8-128.0), respectively. Median number of PR and BT were 2 (1-11) and 3 units (1-28), respectively. After transplantation (median follow-up: 47.5 months), 13 patients (9.7%) had HLA Ab and 10 DSA, mainly directed against class II HLA (HLA Ab: 10/13, DSA: 9/10). The risk of HLA Ab and DSA appearance was significantly lower in patients with PR before transplantation (P = 0.032 and P = 0.009, respectively). The risk of DSA appearance (hazard ratio = 0.17, P = 0.027) remained significantly lower after adjustment on donor age, acute rejection and number of class I/II HLA mismatches. In conclusion, we show that parous women non-immunized are at low risk of HLA Ab production after transplantation.
Assuntos
Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Isoanticorpos/imunologia , Transplante de Rim/imunologia , Modelos Biológicos , Idoso , Transfusão de Sangue , Feminino , Seguimentos , Antígenos HLA/sangue , Antígenos de Histocompatibilidade Classe II/sangue , Humanos , Isoanticorpos/sangue , Pessoa de Meia-Idade , Gravidez/imunologia , Fatores de Tempo , Transplante HomólogoRESUMO
Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepithelial blistering disease, characterized by the presence of antibasement membrane antibodies (BMZ) against anchoring filaments components. An association between the HLA-DQB1*0301 allele and ocular cicatricial pemphigoid has been previously reported in North American Caucasians. In this study, we compared high resolution typing HLA-DRB1 and -DQB1 alleles in 25 CP patients (50 haplotypes) with 106 geographically matched, healthy controls (212 haplotypes), who were all French Caucasians. As in American Caucasians, we confirmed a positive association of CP with the HLA-DQB1*0301 allele which was present in 54% of CP haplotypes (27/50); by contrast 21.7% (46/212) of the matched normal individuals carried the DQB1*0301allele (Pc = 7 x 10(-5); RR = 4.23). HLA-DQB1*0301 is in linkage disequilibrium with several DRB1 alleles. Only the DRB1*1101 DQB1*0301 haplotype frequency was significantly increased (24.0% in CP, 6.6% in control, Pc = 0.002). Furthermore, we observed a decrease of the frequency of the DQB1*02 allele (6% vs 25% in the control group, Pc = 0.05; RR = 0.19). The negative association corresponds to a significant decreased frequency of the DRB1*0701 DQB1*0202 haplotype (0% in CP vs 12.7%, Pc = 0.07 PC) and a non-significant decrease of DRB1*0301 DQB1*0201 (4% in CP vs 12.3%). HLA-DQB1*0301 encodes a negative charge at position DQ 57 (Asp), a critical position in peptide binding to the HLA-DQ molecule groove and therefore we speculate that this molecule may play a role in the selection of BMZ peptides in CP.
Assuntos
Genes MHC da Classe II , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Penfigoide Mucomembranoso Benigno/genética , Alelos , França/epidemiologia , Frequência do Gene , Ligação Genética , Predisposição Genética para Doença , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Penfigoide Mucomembranoso Benigno/imunologia , População Branca/genéticaAssuntos
Formação de Anticorpos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim/imunologia , Distribuição de Qui-Quadrado , Creatinina/sangue , Citotoxicidade Imunológica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Rim/fisiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Results of typing for HLA B27 antigens of 106 patients in whole blood with a FITC monoclonal anti HLA B27 antibody and analysis by flow cytometry are compared to the results obtained by the classical microlymphocytoxicity test. By flow cytometry analysis, there are not false negative result, but, because of cross reactions of the used monoclonal antibody with other specificities of the CREG B7 group, false positive result may be encountered. The flow cytometry analysis for typing HLA B27 antigens using a monoclonal antibody can be a good screening technique: so it's rapid and moreover the negative results can be accepted. The positive results must be confirmed.