背景:肾脏同种异体移植物慢性组织学病变的早期进展是移植物磨损的主要发现。这项回顾性队列研究的目的是阐明HLA组织相容性是否与移植后第一年的慢性组织学病变进展有关。计算了从头供体特异性抗体(dnDSA)形成与HLA错配和微血管炎症(MVI)的既定关联,以与其他研究队列具有可比性。
方法:我们纳入了117名成人肾移植受者,在2016年至2020年期间从主要已故捐赠者移植,在3个月和12个月时进行了监测活检。根据Banff分类评估组织学病变评分。HLA不匹配评分(即eplet,预测间接可识别HLA表位算法(PIRCHE-II),HLA表位错配算法(HLA-EMMA),计算所有移植对的HLA全抗原A/B/DR)。通过单抗原珠定量dnDSA的形成。
结果:超过三分之一的患者在肾小管萎缩(ct)中表现出至少一个班夫等级的慢性病变评分进展,间质纤维化(ci),从3到12个月的活检,在间质纤维化和肾小管萎缩(i-IFTA)区域的小动脉透明(ah)和炎症。多变量比例几率逻辑回归模型显示HLA不匹配评分与组织学病变进展无关联,除了ah,尤其是HLA-EMMADRB1(OR=1.10,95%-CI:1.03-1.18)。此外,在我们的队列中可以证实dnDSA形成与HLA错配和MVI的既定关联(OR=5.31,95%CI:1.19-22.57).
结论:这些数据支持HLA错配和同种免疫反应的关联,同时提示其他因素有助于慢性组织学病变的早期进展。
BACKGROUND: Early progression of chronic histologic lesions in kidney allografts represents the main finding in graft attrition. The objective of this retrospective cohort study was to elucidate whether HLA histocompatibility is associated with progression of chronic histologic lesions in the first year post-transplant. Established associations of de novo donor-specific antibody (dnDSA) formation with HLA mismatch and microvascular inflammation (MVI) were calculated to allow for comparability with other study cohorts.
METHODS: We included 117 adult kidney transplant recipients, transplanted between 2016 and 2020 from predominantly deceased donors, who had surveillance biopsies at 3 and 12 months. Histologic lesion scores were assessed according to the Banff classification. HLA mismatch scores [i.e. eplet, predicted indirectly recognizable HLA-epitopes algorithm (PIRCHE-II), HLA epitope mismatch algorithm (HLA-EMMA), HLA whole antigen A/B/DR] were calculated for all transplant pairs. Formation of dnDSAs was quantified by single antigen beads.
RESULTS: More than one-third of patients exhibited a progression of chronic lesion scores by at least one Banff grade in tubular atrophy (ct), interstitial fibrosis (ci), arteriolar hyalinosis (ah) and inflammation in the area of interstitial fibrosis and tubular atrophy (i-IFTA) from the 3- to the 12-month biopsy. Multivariable proportional odds logistic regression models revealed no association of HLA mismatch scores with progression of histologic lesions, except for ah and especially HLA-EMMA DRB1 [odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.03-1.18]. Furthermore, the established associations of dnDSA formation with HLA mismatch and MVI (OR = 5.31, 95% CI 1.19-22.57) could be confirmed in our cohort.
CONCLUSIONS: These data support the association of HLA mismatch and alloimmune response, while suggesting that other factors contribute to early progression of chronic histologic lesions.