Tagliamacco Augusto, Cioni Michela, Comoli Patrizia, Ramondetta Miriam, Brambilla Caterina, Trivelli Antonella, Magnasco Alberto, Biticchi Roberta, Fontana Iris, Dulbecco Pietro, Palombo Domenico, Klersy Catherine, Ghiggeri Gian Marco, Ginevri Fabrizio, Cardillo Massimo, Nocera Arcangelo
Transplant Immunology Research Laboratory at Clinical Nephrology and Gastroenterology Units, Department of Internal Medicine -DIMI, University of Genova, Genova, Italy.
Transpl Int. 2014 Jul;27(7):667-73. doi: 10.1111/tri.12316. Epub 2014 Apr 25.
Data on the different HLA-antibody (Ab) categories in pediatric kidney recipients developing de novo donor-specific Abs (DSA) after transplantation are scarce. We retrospectively evaluated 82 consecutive nonsensitized pediatric recipients of a first kidney graft for de novo HLA Ab occurrence and antigen specificity. At a median follow-up of 6 years, 29% of patients developed de novo DSA, while 45% had de novo non-DSA. DSA appeared at 25-month median time post-transplant and were mostly directed toward HLA-DQ antigens. Considering each HLA antigen, the estimated rate of DQ DSA (7.55 per 100 person-years) was much higher than the rates observed for non-DQ DSA. The HLA-DQ Ab recognized determinants of the DQβ chain in 70% of cases, α chain in 25% of cases, and both chains in one patient. Non-DSA peaked earlier than DSA, and were largely directed against HLA class I specificities that belonged to HLA-A- and HLA-B-related cross-reacting epitope groups (CREG) in 56% of cases. Our results indicate a need for evaluating HLA-DQ compatibilities in kidney allocation, in order to minimize post-transplant development of de novo DSA, known to be responsible for antibody-mediated rejection and graft loss.
关于小儿肾移植受者移植后出现新发供者特异性抗体(DSA)的不同HLA抗体(Ab)类别的数据很少。我们回顾性评估了82例连续的首次肾移植未致敏小儿受者新发HLA抗体的发生情况和抗原特异性。中位随访6年时,29%的患者出现新发DSA,而45%的患者出现新发非DSA。DSA在移植后中位时间25个月出现,主要针对HLA-DQ抗原。考虑每种HLA抗原,DQ DSA的估计发生率(每100人年7.55例)远高于非DQ DSA的发生率。70%的病例中,HLA-DQ抗体识别DQβ链的决定簇,25%的病例中识别α链的决定簇,1例患者中识别两条链的决定簇。非DSA的峰值早于DSA,且在56%的病例中主要针对属于HLA-A和HLA-B相关交叉反应表位组(CREG)的HLA I类特异性。我们的结果表明,有必要在肾脏分配中评估HLA-DQ相容性,以尽量减少移植后新发DSA的发生,已知新发DSA会导致抗体介导的排斥反应和移植物丢失。