Salazar Israel D R, Merino López Maribel, Chang Jessica, Halloran Philip F
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada; Department of Medicine, Viedma Hospital, Cochabamba, Bolivia; Caja National Health Hospital, Cochabamba, Bolivia; and.
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada;
J Am Soc Nephrol. 2015 Dec;26(12):3190-8. doi: 10.1681/ASN.2014111064. Epub 2015 Apr 27.
Intimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell-mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.
肾移植活检标本中的内膜动脉炎（血管病变的存在）被认为具有重要的预后和诊断意义。我们评估了703份指征性活检标本中血管病变与预后的关系，并使用基于微阵列的分子检测重新审视血管病变与排斥反应的关系。在49份标本（7%）中发现了血管病变，且通常为轻度（v1）。与无血管病变相比，血管病变的存在对移植物存活没有影响。按照当前惯例，病理学家几乎总是将血管病变解释为反映T细胞介导的排斥反应（TCMR），无论是单纯的还是与抗体介导的排斥反应（ABMR）混合的。分子评分对49份标本中的29份（59%）的传统诊断提出了质疑，其中包括10份传统上诊断为TCMR但无分子排斥反应的标本，以及9份传统上诊断为TCMR且分子上与纯ABMR混合的标本。符合TCMR标准的肾小管间质炎症（i-t）的存在，使得血管病变标本可分为21份i-t-血管病变标本和28份孤立性血管病变标本。分子TCMR评分在95%的i-t-血管病变标本中呈阳性，但在孤立性血管病变标本中仅为21%。分子ABMR评分在孤立性血管病变活检中通常呈阳性（46%）。移植后活检时间对于理解孤立性血管病变至关重要：大多数早期孤立性血管病变标本无分子排斥反应且DSA阴性，而大多数移植后>1年的孤立性血管病变标本DSA和ABMR评分呈阳性。因此，指征性活检标本中的血管病变不影响预后，可反映TCMR、ABMR或无排斥反应。移植后的时间、DSA和伴随的炎症为解释血管病变提供了概率依据。
