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Subthreshold rejection activity in many kidney transplants currently classified as having no rejection
American Journal of Transplantation ( IF 8.9 ) Pub Date : 2024-08-06 , DOI: 10.1016/j.ajt.2024.07.034 Philip F Halloran 1 , Katelynn S Madill-Thomsen 2 , Georg Böhmig 3 , Jonathan Bromberg 4 , Klemens Budde 5 , Meagan Barner 6 , Martina Mackova 2 , Jessica Chang 2 , Gunilla Einecke 7 , Farsad Eskandary 3 , Gaurav Gupta 8 , Marek Myślak 9 , Ondrej Viklicky 10 , Enver Akalin 11 , Tarek Alhamad 12 , Sanjiv Anand 13 , Miha Arnol 14 , Rajendra Baliga 15 , Mirosław Banasik 16 , Adam Bingaman 17 , Christopher D Blosser 18 , Daniel Brennan 19 , Andrzej Chamienia 20 , Kevin Chow 21 , Michał Ciszek 22 , Declan de Freitas 23 , Dominika Dęborska-Materkowska 24 , Alicja Debska-Ślizień 25 , Arjang Djamali 26 , Leszek Domański 27 , Magdalena Durlik 28 , Richard Fatica 29 , Iman Francis 30 , Justyna Fryc 31 , John Gill 32 , Jagbir Gill 32 , Maciej Glyda 33 , Sita Gourishankar 1 , Ryszard Grenda 34 , Marta Gryczman 35 , Petra Hruba 36 , Peter Hughes 21 , Arskarapurk Jittirat 37 , Zeljka Jurekovic 38 , Layla Kamal 39 , Mahmoud Kamel 15 , Sam Kant 40 , Bertram Kasiske 41 , Nika Kojc 42 , Joanna Konopa 20 , James Lan 32 , Roslyn Mannon 43 , Arthur Matas 44 , Joanna Mazurkiewicz 45 , Marius Miglinas 46 , Thomas Müller 47 , Seth Narins 48 , Beata Naumnik 31 , Anita Patel 30 , Agnieszka Perkowska-Ptasińska 24 , Michael Picton 49 , Grzegorz Piecha 50 , Emilio Poggio 51 , Silvie Rajnochová Bloudíčkova 52 , Milagros Samaniego-Picota 53 , Thomas Schachtner 54 , Sung Shin 55 , Soroush Shojai 56 , Majid L N Sikosana 1 , Janka Slatinská 36 , Katarzyna Smykal-Jankowiak 33 , Ashish Solanki 57 , Željka Veceric Haler 14 , Ksenija Vucur 58 , Matthew R Weir 59 , Andrzej Wiecek 50 , Zbigniew Włodarczyk 60 , Harold Yang 61 , Ziad Zaky 62
American Journal of Transplantation ( IF 8.9 ) Pub Date : 2024-08-06 , DOI: 10.1016/j.ajt.2024.07.034 Philip F Halloran 1 , Katelynn S Madill-Thomsen 2 , Georg Böhmig 3 , Jonathan Bromberg 4 , Klemens Budde 5 , Meagan Barner 6 , Martina Mackova 2 , Jessica Chang 2 , Gunilla Einecke 7 , Farsad Eskandary 3 , Gaurav Gupta 8 , Marek Myślak 9 , Ondrej Viklicky 10 , Enver Akalin 11 , Tarek Alhamad 12 , Sanjiv Anand 13 , Miha Arnol 14 , Rajendra Baliga 15 , Mirosław Banasik 16 , Adam Bingaman 17 , Christopher D Blosser 18 , Daniel Brennan 19 , Andrzej Chamienia 20 , Kevin Chow 21 , Michał Ciszek 22 , Declan de Freitas 23 , Dominika Dęborska-Materkowska 24 , Alicja Debska-Ślizień 25 , Arjang Djamali 26 , Leszek Domański 27 , Magdalena Durlik 28 , Richard Fatica 29 , Iman Francis 30 , Justyna Fryc 31 , John Gill 32 , Jagbir Gill 32 , Maciej Glyda 33 , Sita Gourishankar 1 , Ryszard Grenda 34 , Marta Gryczman 35 , Petra Hruba 36 , Peter Hughes 21 , Arskarapurk Jittirat 37 , Zeljka Jurekovic 38 , Layla Kamal 39 , Mahmoud Kamel 15 , Sam Kant 40 , Bertram Kasiske 41 , Nika Kojc 42 , Joanna Konopa 20 , James Lan 32 , Roslyn Mannon 43 , Arthur Matas 44 , Joanna Mazurkiewicz 45 , Marius Miglinas 46 , Thomas Müller 47 , Seth Narins 48 , Beata Naumnik 31 , Anita Patel 30 , Agnieszka Perkowska-Ptasińska 24 , Michael Picton 49 , Grzegorz Piecha 50 , Emilio Poggio 51 , Silvie Rajnochová Bloudíčkova 52 , Milagros Samaniego-Picota 53 , Thomas Schachtner 54 , Sung Shin 55 , Soroush Shojai 56 , Majid L N Sikosana 1 , Janka Slatinská 36 , Katarzyna Smykal-Jankowiak 33 , Ashish Solanki 57 , Željka Veceric Haler 14 , Ksenija Vucur 58 , Matthew R Weir 59 , Andrzej Wiecek 50 , Zbigniew Włodarczyk 60 , Harold Yang 61 , Ziad Zaky 62
Affiliation
Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell–mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.
中文翻译：
目前被归类为无排斥反应的许多肾移植中的亚阈值排斥反应活性
大多数接受活检的肾移植患者根据共识阈值被归类为无排斥反应。然而，我们假设由于这些患者具有正常的适应性免疫系统，因此 T 细胞介导的排斥反应 （TCMR） 和抗体介导的排斥反应 （ABMR） 可能在目前归类为无排斥反应的一些移植中作为亚阈值活性存在。为了解决这个问题，我们研究了 5086 例肾移植活检 （来自 4170 例患者） 的全基因组微阵列结果。一项更新的分子原型分析将 56% 的活检指定为无排斥反应。在许多归类为无排斥反应的活检中，亚阈值分子 TCMR 和/或 ABMR 活性分子活性可检测到分类器评分升高，在许多 TCMR 活检中检测到 ABMR 活性，在许多 ABMR 活检中检测到 TCMR 活性。在组织学和分子学分类为无排斥反应的活检中，分子 TCMR 分类器评分与组织学 TCMR 特征和分子损伤的增加相关，估计肾小球滤过率较低，移植物丢失风险较高，分子 ABMR 活性与肾小球炎和供体特异性抗体增加相关。无排斥反应活检 亚阈值 TCMR 或 ABMR 活性高，在未来活检中分别诊断出 TCMR 或 ABMR 的可能性更高。我们得出的结论是，许多肾移植受者具有未被识别的阈下 TCMR 或 ABMR 活性，对未来的问题具有重大影响。
更新日期：2024-08-06
中文翻译：
目前被归类为无排斥反应的许多肾移植中的亚阈值排斥反应活性
大多数接受活检的肾移植患者根据共识阈值被归类为无排斥反应。然而，我们假设由于这些患者具有正常的适应性免疫系统，因此 T 细胞介导的排斥反应 （TCMR） 和抗体介导的排斥反应 （ABMR） 可能在目前归类为无排斥反应的一些移植中作为亚阈值活性存在。为了解决这个问题，我们研究了 5086 例肾移植活检 （来自 4170 例患者） 的全基因组微阵列结果。一项更新的分子原型分析将 56% 的活检指定为无排斥反应。在许多归类为无排斥反应的活检中，亚阈值分子 TCMR 和/或 ABMR 活性分子活性可检测到分类器评分升高，在许多 TCMR 活检中检测到 ABMR 活性，在许多 ABMR 活检中检测到 TCMR 活性。在组织学和分子学分类为无排斥反应的活检中，分子 TCMR 分类器评分与组织学 TCMR 特征和分子损伤的增加相关，估计肾小球滤过率较低，移植物丢失风险较高，分子 ABMR 活性与肾小球炎和供体特异性抗体增加相关。无排斥反应活检 亚阈值 TCMR 或 ABMR 活性高，在未来活检中分别诊断出 TCMR 或 ABMR 的可能性更高。我们得出的结论是，许多肾移植受者具有未被识别的阈下 TCMR 或 ABMR 活性，对未来的问题具有重大影响。
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