Soluble HLA-G levels in heart transplant recipients: Dynamics and correlation with clinical outcomes.

PURPOSE: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. METHODS: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. RESULTS: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. CONCLUSIONS: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.

Mitochondrial DNA haplogroups influence the risk of aortic stenosis.

AIM: The underlying pathophysiologic mechanisms of aortic stenosis are not clear. Mitochondrial dysfunction plays a role in many pathological conditions including cardiac diseases. We aimed to analyze the mitochondrial DNA haplogroups in a group of patients undergoing valve replacement surgery due to severe aortic stenosis. METHODS: Mitochondrial DNA haplogroups were assessed in 176 patients with severe aortic stenosis and 308 control subjects. Cardiovascular risk factors and demographics were similar in both groups. RESULTS: Patients carrying haplogroup Uk had a lower risk of developing aortic stenosis, especially compared to patients carrying haplogroup H (odds ratio = 0.507; 95% confidence interval: 0.270-0.952, p = 0.035). CONCLUSIONS: Mitochondrial DNA haplogroups could be involved in the development of severe aortic stenosis. Specifically, haplogroup H could be a risk factor and Uk a protective factor for severe aortic stenosis in a population from Spain.

Anatomopathological and immunohistochemical study of explanted cryopreserved arteries.

BACKGROUND: The aim of the study was to analyze the mechanism of deterioration of implanted arteries. METHODS: Eleven patients were included. Samples of vascular segments obtained from multiorgan donors and samples of the same vascular segments after explantation in the recipient were analyzed. Blood group, time of cold and warm ischemia, cause of death, time spent in the intensive care unit, time of storage of the cryopreserved grafts, and anatomopathological and immunohistochemical studies were analyzed using the preimplant samples obtained from the multiorgan donor. For samples obtained from the recipient, blood group, duration for which the tissue from the donor has been implanted, reason for graft explantation, and anatomopathological and immunohistochemical studies were analyzed. RESULTS: Histopathologically, the main finding has been the substitution of the muscular cap of the arterial wall by an intense fibrosis, in most of the cases, of a symmetrical nature. Besides this degeneration of myocytes, there is marked perivascular fibrosis and fibrointimal thickening also exists. The T lymphocytes suggest the importance of the immunological mechanism in the distortion of the architecture of the arteries. The atherosclerosis plays a less relevant role. CONCLUSIONS: Evidence of immune-mediated injury was found, and this mechanism seems to be responsible for the degenerative process in cryopreserved homografts.

Culture of limbal stem cells on human amniotic membrane.

Limbal stem cells (LSC) have an important role in the maintenance of the corneal surface epithelium, and autologous cultured limbal epithelial cell (HLECs) transplantations have contributed substantially to the treatment of the visually disabling condition known as LSC deficiency. A major challenge is the ability to identify LSC in vitro and in situ, and one of the major controversies in the field relates to reliable LSC markers. This study was carried out to evaluate the culture of a limbal biopsy on human amniotic membrane (HAM): directly on the chorionic side and on intact epithelium, and the expression of the stem cell associated markers: ABCG2, p63. HAM has been extensively used for ocular surface reconstruction and has properties which facilitate the growth of epithelial cells controlling inflammation and scarring.