Transplantation · 2025
Enhanced Diagnosis of Chronic Antibody-mediated Rejection Using Peritubular Capillary Multilayering.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nankivell Brian J, Shingde Meena, P'Ng Chow Heok, Tran Thomas
Аннотация
BACKGROUND: Peritubular capillary multilayering (PTCML) of basement membranes is an ultrastructural feature of chronic antibody-mediated rejection (AMR) with uncertain diagnostic thresholds.
METHODS: This single-center, prospective cohort study evaluated the relationships of PTCML with chronic AMR in 2541 kidney samples from 1195 recipients.
RESULTS: Epidemiological modeling found that younger recipients, living donation, early AMR, pulse corticosteroid rejection treatment, later presentation, and higher donor-specific antibody strength were clinical risk factors for an abnormal PTCML score of ≥3. The total number of PTC layers was correlated with posttransplant time, AMR histology, donor-specific antibody positivity, renal dysfunction, proteinuria, and graft failure. Histological Banff cg, ptc, C4d ptc , and C4d glom independently predicted PTCML ≥3. Mild PTCML of 3-4 layers with circumferential remodeling in multiple PTC showed 82.9% sensitivity and 72.7% specificity against the Banff cg≥1a reference test, verified using Banff 2022 AMR criteria, and considered "suspicious" for chronic AMR. PTCML ≥5 correlated with late graft failure. Normal PTC (n = 322) in early protocol samples showed 1 basement membrane layer, except for 12.5% with mild segmental reduplication involving 13.7 ± 10.2% capillary circumference. Circumferential scoring efficiently separated mild segmental PTCML from normal variability against pathological AMR multilayering. The poor 30.0% sensitivity and 91.1% specificity (n = 374 late indication biopsies, 2029 PTCs) of the Banff 2013 AMR criteria improved to 55.0% and 89.7% using modified PTCML ≥7 or 2×PTCML ≥5 criteria, which allowed for a diagnostic disease "rule-in."
CONCLUSIONS: Circumferential multilayering from PTCML ≥3 replicated across multiple capillaries optimally recognized mild chronic AMR as a superior histological marker of chronic tissue injury with high sensitivity. These ultrastructural diagnostic criteria for the detection of early chronic AMR phenotypes require multicenter validation.
METHODS: This single-center, prospective cohort study evaluated the relationships of PTCML with chronic AMR in 2541 kidney samples from 1195 recipients.
RESULTS: Epidemiological modeling found that younger recipients, living donation, early AMR, pulse corticosteroid rejection treatment, later presentation, and higher donor-specific antibody strength were clinical risk factors for an abnormal PTCML score of ≥3. The total number of PTC layers was correlated with posttransplant time, AMR histology, donor-specific antibody positivity, renal dysfunction, proteinuria, and graft failure. Histological Banff cg, ptc, C4d ptc , and C4d glom independently predicted PTCML ≥3. Mild PTCML of 3-4 layers with circumferential remodeling in multiple PTC showed 82.9% sensitivity and 72.7% specificity against the Banff cg≥1a reference test, verified using Banff 2022 AMR criteria, and considered "suspicious" for chronic AMR. PTCML ≥5 correlated with late graft failure. Normal PTC (n = 322) in early protocol samples showed 1 basement membrane layer, except for 12.5% with mild segmental reduplication involving 13.7 ± 10.2% capillary circumference. Circumferential scoring efficiently separated mild segmental PTCML from normal variability against pathological AMR multilayering. The poor 30.0% sensitivity and 91.1% specificity (n = 374 late indication biopsies, 2029 PTCs) of the Banff 2013 AMR criteria improved to 55.0% and 89.7% using modified PTCML ≥7 or 2×PTCML ≥5 criteria, which allowed for a diagnostic disease "rule-in."
CONCLUSIONS: Circumferential multilayering from PTCML ≥3 replicated across multiple capillaries optimally recognized mild chronic AMR as a superior histological marker of chronic tissue injury with high sensitivity. These ultrastructural diagnostic criteria for the detection of early chronic AMR phenotypes require multicenter validation.