Innate immunity in myasthenia gravis thymus: Pathogenic effects of Toll-like receptor 4 signaling on autoimmunity

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Inflammation and Epstein-Barr Virus Infection Are Common Features of Myasthenia Gravis Thymus: Possible Roles in Pathogenesis

The thymus plays a major role in myasthenia gravis (MG). Our recent finding of a persistent Epstein-Barr (EBV) virus infection in some MG thymuses, combined with data showing that the thymus is in a proinflammatory state in most patients, supports a viral contribution to the pathogenesis of MG. Aim of this study was to gain further evidence for intrathymic chronic inflammation and EBV infection in MG patients. Transcriptional profiling by low density array and real-time PCR showed overexpression of genes involved in inflammatory and immune response in MG thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins confirmed an active intrathymic EBV infection, further supporting the hypothesis that EBV might contribute to onset or perpetuation of the autoimmune response in MG. Altogether, our results support a role of inflammation and EBV infection as pathogenic features of MG thymus

IMMEDIATE CAUSES OF DEATH IN SHORT-TERM SURVIVING HEART-TRANSPLANT RECIPIENTS

From 1985 to 1992, 1068 cardiac transplants have been performed in the Italian units. The immediate causes of death of 142 of the 148 orthotopic cardiac transplantation recipients who died within the first 6 postoperative months were surveyed. Deaths were grouped into three periods: perioperative (less than or equal to 1 month, 68.3%), early (>1 less than or equal to 3 months, 23.2%), and advanced (>3 less than or equal to 6 months, 8.5%). Acute graft failure (arising from the ischemic damage to the donor heart, from surgical problems, from severe pulmonary hypertension, or from multiorgan failure) accounted for 49% of perioperative deaths and, along with noncardiac emergencies (23% of perioperative deaths), was significantly more frequent in this period than in the subsequent ones. The dissection of thoracic arteries was responsible for 4% of postoperative deaths, occurring exclusively among patients transplanted for ischemic or valvular heart disease. In the early and advanced periods, untreatable acute rejection (13%) and fatal infections (38%), mostly saprophytic, were significantly more frequent. Ischemic heart damage secondary to graft vasculopathy already caused 26% of deaths between the fourth and sixth months after transplantation. Some diseases, such as acute rejection, had the same frequency as both underlying disease and immediate cause of death. On the contrary, graft failure is more common as primary disease, leading to death also through noncardiac complications and saprophytic infections. Bacterial infections have the same frequency as both prime and immediate cause of death, viral infections are more common as primary disease, and the opposite is true for saprophytic infections

WHEN AND WHY DO HEART-TRANSPLANT RECIPIENTS DIE - A 7 YEAR EXPERIENCE OF 1068 CARDIAC TRANSPLANTS

This mortality study deals with the 1068 heart transplants (1054 patients) performed in Italian Units from November 1985 to April 1992. The death rate was 19.7% and the actuarial survival was 89% at 1 month, 83% at 1 year and 74% at 6.5 years. Recipients who died had been less often transplanted for dilated cardiomyopathy, were older (44.1 vs. 41.7 years) and more often male (84.5 vs. 72.7%). Analysis of the causes of death was restricted to orthotopic transplantations (1029/1068 procedures, 195/208 deaths). Deaths were grouped within four intervals: peri-operative (less-than-or-equal-to 1 month, 50.0% of deaths), early (> 1 month less-than-or-equal-to 3 months, 17.2%), intermediate (> 3 months less-than-or-equal-to 2 years, 22.6%) and late (> 2 years, 10.2%). The prime causes of death were mostly post-operative graft failure (whose effects brought about 64% of peri-operative deaths, 28% of early and 7% of intermediate deaths), post-operative complications (10% of peri-operative deaths), acute rejection (10% of total deaths, distributed in all the periods), graft arteriopathy (6% of early, 36% of intermediate and 58% of late deaths), infections (17% of deaths, occurring in all periods but late) and malignant tumours (7% of deaths), lymphomas being the first to occur and Kaposi's sarcoma occuring only in the intermediate period. Repeat transplantation had a poor outcome (death rate 71.4%), two-thirds of the re-transplanted patients' deaths being due to early graft failure and a third to late relapsing graft vasculopathy