Immunosenescence, immunotolerance and rejection: clinical aspects in solid organ transplantation.

As a consequence of increased lifespan and rising number of elderly individuals developing end-stage organ disease, the higher demand for organs along with a growing availability for organs from older donors pose new challenges for transplantation. During aging, dynamic adaptations in the functionality and structure of the biological systems occur. Consistently, immunosenescence (IS) accounts for polydysfunctions within the lymphocyte subsets, and the onset of a basal but persistent systemic inflammation characterized by elevated levels of pro-inflammatory mediators. There is an emerging consensus about a causative link between such hallmarks and increased susceptibility to morbidities and mortality, however the role of IS in solid organ transplantation (SOT) remains loosely addressed. Dissecting the immune-architecture of immunologically-privileged sites may prompt novel insights to extend allograft survival. A deeper comprehension of IS in SOT might unveil key standpoints for the clinical management of transplanted patients.

Sicilian centenarian offspring are more resistant to immune ageing.

BACKGROUND: Immunosenescence constitutes a major indirect cause of morbidity and mortality in the elderly. Previous analysis of immune signatures in a cohort of centenarian offspring showed an intermediate immunophenotype between age-matched and younger controls. AIMS: To confirm and extend the previous studies performing further phenotypical analysis in centenarian offspring and controls. METHODS: Analysis of Treg cells, γδ T cells, mucosal-associated invariant T cells, and senescent immune T cells was performed in centenarian offspring and controls. RESULTS: We report significant differences between elderly and centenarian offspring in most of the studied subsets, showing that centenarian offspring subsets present an intermediate phenotyping between elderly and younger people. CONCLUSION: The whole present data confirm and extend the previous results showing that centenarian offspring retain more youthful immunological parameters and that the exhaustion of the immune system is less evident than in elderly without centenarian parents, though further investigations are warranted.

Immune aging, dysmetabolism, and inflammation in neurological diseases.

As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as "inflammaging". Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders.

Descemet membrane endothelial keratoplasty in vitrectomized eyes: clinical results.

PURPOSE: The aim of this study was to evaluate clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) in vitrectomized eyes. METHODS: Medical records were reviewed for demographics, baseline and follow-up best spectacle-corrected visual acuities (BCVAs), endothelial cell densities, and indication for DMEK. Operative notes were analyzed to identify any specific intraoperative event. RESULTS: A total of 281 DMEK cases were reviewed. Twenty cases were considered eligible for the study. Seven eyes had a history of anterior vitrectomy, and 13 eyes had a history of complete removal of the vitreous body. Ages ranged from 37 to 78 years (mean, 62.9 years) and mean follow-up after DMEK was 11.2 months (range, 3-29 months). The preoperative mean BCVA was 1.4 ± 0.5 logarithm of minimum angle of resolution (logMAR) and increased to 1.0 ± 0.5 logMAR after 4 weeks (P = 0.0290). After 6-month and 12-month follow-up, BCVA was 0.8 ± 0.6 logMAR (P = 0.0055) and 0.6 ± 0.3 logMAR (P = 0.0001), respectively. All cases had ocular comorbidities affecting the BCVA. In 13 cases, significant intraoperative complications were experienced. In the immediate postoperative period, iatrogenic primary graft failure was reported in 2 eyes (2/20). In 4 eyes, late graft failure was observed. Two eyes had exacerbation of preexisting glaucoma. Mean preoperative endothelial cell density was 2301 ± 159 cells per square millimeter; postoperative follow-up visits at 6 and 12 months showed a decrease to 1398 ± 161 cells per square millimeter and 1241 ± 155 cells per square millimeter, respectively. CONCLUSIONS: DMEK seems to be successful in restoring visual acuity even in vitrectomized eyes. Nevertheless, the overall complication rate was higher than that in standard DMEK.

Immune profiling of Alzheimer patients.

Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-ß peptide (Aß). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aß present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.