The frequency and avidity of committed cytotoxic T lymphocytes (cCTL) for donor HLA class I and class II antigens and their relation with graft vascular disease

Cellular immune processes may trigger the development of graft vascular disease (GVD). CD4 and CD8 cytotoxic T lymphocytes that infiltrate the allograft could play a role in the development of GVD. We studied the presence of in vivo primed or committed CTL (cCTL) and their avidity for donor HLA class I and class II antigens in graft-infiltrating lymphocyte cultures propagated from endomyocardial biopsies derived from patients with and without signs of GVD. The fraction of cCTL with high avidity for HLA class I or class II antigens was estimated by the addition of anti-CD8 or anti-CD4 MoAbs to the cytotoxic phase of the limiting dilution analysis. In the first year after transplantation no difference in the frequency of donor-specific class I cCTL between patients with and without GVD was found. Addition of anti-CD8 MoAb revealed that most cultures predominantly consisted of cCTL with low avidity for donor HLA class I antigens, irrespective of the development of GVD at 1 year after transplantation. However, in patients who did not develop GVD, the frequency of cCTL with donor HLA class II specificity was significantly higher than in patients who did develop GVD. The avidity for donor HLA class II antigens was comparable in both groups. A high frequency of donor-specific cCTL for HLA class II antigens seems to be a protective factor against the development of GVD. These cCTL might be cytotoxic for cells involved in GVD development, e.g. activated endothelium and smooth muscle cells of donor origin

Adult attention deficit hyperactivity disorder (ADHD) in ASD

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by core symptoms of inattention, impulsivity, and hyperactivity. ADHD has been considered for a long time as a childhood condition, fading as children grew up. Instead, ADHD changes its clinical presentation over the lifespan, but persists in most cases in adulthood with its associated impairment. It is only since 2013, with the release of DSM-5, that it is possible to diagnose ADHD in the presence of ASD. This change was based on studies performed in children, adolescents, and adults that found high comorbidity rates between ASD and ADHD. Studies investigating the co-occurrence of such disorders at a genetic, at structural and functional neuroimaging levels indicate that they share common genetic risk factors, involve similar biological mechanisms, and affect the same brain regions. The co-existence of both disorders causes a significant burden. Individuals with ASD presenting ADHD symptomatology exhibit a more severe phenotype, with more autistic traits, greater impairment in adaptive behavior, and increased risk for developing additional psychiatric conditions. Pharmacotherapeutic treatments for ADHD, such as methylphenidate and atomoxetine, have been studied in individuals with ADHD+ASD, demonstrating efficacy in decreasing the severity of ADHD symptoms, although with lower effect sizes than in people with only ADHD. The diagnosis of ADHD is established clinically and requires the use of rating scales as well as clinical interviews for avoiding the risk of misdiagnosis. The stigma surrounding individuals with ADHD is huge, therefore it is necessary to increase awareness about this disorder among both the public and healthcare professionals, in order to reduce the barriers that patients face to get access to proper diagnosis and treatment