Summary
Pediatric recipients of living‐donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi‐allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post‐Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr‐tol), but not in 50 intolerant patients (Gr‐intol). The Gr‐intol consisted of 24 patients with rejection (Gr‐rej) and 26 with fibrosis of grafts (Gr‐fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11–7.02, P = 0.03], was a positive independent predictor, whereas HLA‐A mismatch (0.18, 0.03–0.91, P = 0.04) was a negative predictor. HLA‐DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr‐intol (4.9%) compared with Gr‐tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr‐Tol (P = 0.02). Although HLA‐B mismatch (8.73, 1.09–70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA‐A match and the later predominance of Tregs are factors associated with OT.
This is the first report providing detailed evidence that donor-specific naïve-Tregs were generated and their suppressive properties were upregulated in the peripheral blood of tolerant patients, whereas their frequency was downregulated in intolerant patients. Therefore, we speculate that not only conventional-Tregs play a role in Tx tolerance but also the role of naïve-Tregs is critical.
We usually use spirometry for the medical follow-up of respiratory mechanics after lung transplantation. However, especially in the first few post-operative weeks, it is easily affected by postoperative pain and the patient's co-operation during forced breathing effort. To avoid missing out on assessing pulmonary function, we perform non-invasive forced oscillation techniques on the patients who cannot perform forced breathing maneuvers. In this paper, we discuss the application of forced oscillation techniques on a patient with suspicion of acute lung rejection, whose spirometry could not be correctly performed and seemed to be unreliable. The respiratory impedance measurements had good correlation with the patient's clinical symptoms before and after steroid therapy. Thus, postoperative pulmonary function follow-up using forced oscillation technique was useful in assessing peripheral airway condition in critically ill patients, and may be able to detect acute rejection.
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