Cyclosporine C2 Target Levels and Acute Cellular Rejection After Lung Transplantation

Abstract Background Hypercapnia alleviates pulmonary ischemia–reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Methods Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague–Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague–Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. Results The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8+ T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4+ T cells, and interleukin-10 levels were similar between groups. Conclusions Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

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Disease Recurrence and Acute Cellular Rejection Episodes During the First Year After Lung Transplantation Among Patients With Sarcoidosis

Transplantation Journal ◽

10.1097/tp.0000000000000673 ◽

2015 ◽

Vol 99 (9) ◽

pp. 1940-1945 ◽

Cited By ~ 10

Author(s):

Amit Banga ◽

Debasis Sahoo ◽

Charles R. Lane ◽

Carol F. Farver ◽

Marie M. Budev

Keyword(s):

Lung Transplantation ◽

Disease Recurrence ◽

Acute Cellular Rejection ◽

First Year ◽

Cellular Rejection

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Donor-derived, Cell-free DNA levels by Next Generation Targeted Sequencing are Elevated in Allograft Rejection after Lung Transplantation

ERJ Open Research ◽

10.1183/23120541.00462-2020 ◽

2020 ◽

pp. 00462-2020

Author(s):

KK Khush ◽

I De Vlaminick ◽

H Luikart ◽

DJ Ross ◽

M Nicolls

Keyword(s):

Lung Transplantation ◽

Predictive Value ◽

Tissue Injury ◽

Acute Cellular Rejection ◽

Targeted Sequencing ◽

Next Generation ◽

Cell Free Dna ◽

Chronic Lung Allograft Dysfunction ◽

Free Dna ◽

Cellular Rejection

Surveillance after lung transplantation (LT) is critical to the detection of acute cellular rejection (ACR) and prevention of Chronic Lung Allograft Dysfunction (CLAD). Therefore, we measured donor-derived cell-free DNA (dd-cfDNA) implementing a clinical-grade, next generation targeted sequencing assay in 107 plasma samples from 38 unique LT recipients with diagnostic cohorts classified as: (1) Biopsy-confirmed or treated acute cellular rejection (ACR), (2) antibody-mediated rejection (AMR), (3) Obstructive chronic lung allograft dysfunction (CLAD), (4) allograft infection (INFXN), and (5) Stable healthy allografts (STABLE). Our principal findings: (1) dd-cfDNA level was elevated in ACR (median 0.91%; IQR: 0.39–2.07%), CLAD (2.06%; IQR: 0.57–3.67%), and an aggregated cohort of rejection encompassing allograft injury (1.06%; IQR :0.38–2.51%), compared with the STABLE cohort (0.38%; IQR: 0.23–0.87%) (p=0.02). (2) dd-cfDNA level with AMR was elevated (1.34%; IQR: 0.34–2.40%) compared to STABLE although did not reach statistical significance (p=0.07) due to limitations in sample size. (3) No difference in dd-cfDNA for allograft INFXN (0.39%; IQR: 0.18–0.67%) versus STABLE, that may relate to differences in “tissue injury” with spectrum of bronchial colonisation versus invasive infection. (4) No difference for dd-cfDNA in unilateral versus bilateral LT. (5) “Optimal Threshold” for dd-cfDNA for aggregated rejection events representing allograft injury was determined as 0.85%, with Sensitivity=55.6%, Specificity=75.8%, Positive Predictive Value (PPV)=43.3%, and Negative Predictive Value (NPV)=83.6%. Measurement of plasma dd-cfDNA may be a clinically useful tool for the assessment of lung allograft health and surveillance for “tissue injury” with a spectrum of rejection.

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