Roberto Pagni

Autoimmune events during interferon beta-1b treatment for multiple sclerosis.

Autoimmune events, although rarely reported during interferon beta-1b (IFNB) treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more frequent than expected due to the many immunologic abnormalities associated with this disease. We report the prospective two-year follow-up of autoimmune events in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid and liver function and serum level of 12 autoantibodies (autoAbs) against organ- (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were associated with thyroid or liver function alteration in many cases. Persistent autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of whom were women with a familial history of thyroid disease or baseline anti-thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid dysfunction was adequately treated without stopping IFNB. Liver function alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs in four) was transient and did not require IFNB treatment to be stopped, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune events may occur, indicating that thyroid and liver function and autoAbs must be carefully monitored.

Antiglycan antibodies as serological markers in the differential diagnosis of inflammatory bowel disease

Background: The objective of the study was to evaluate the diagnostic accuracy of recently developed antiglycan serological tests in clinical practice for the diagnosis of Crohns disease. Methods: This study was a cohort analysis of both clinical and biochemical parameters of patients with diagnosed inflammatory bowel disease compared with those in a control population. Antiglycan antibodies were determined using commercially available enzyme immunoassays. The setting was the outpatient unit of the gastroenterology department of a large, tertiary‐care referral academic hospital. Participants were 214 consecutive patients, enrolled over a 5‐month period, including 116 with Crohns disease and 53 with ulcerative colitis, as well as 45 with other gastrointestinal diseases and 51 healthy controls. Results: Anti–Saccharomyces cerevisiae antibodies showed the best performance (54% sensitivity and 88%–95% specificity for Crohns disease). Among patients with negative anti‐Saccharomyces antibodies, 19 (34%) had high titers of at least another tested antiglycan antibody. Anti‐Saccharomyces and anti‐laminaribioside antibodies were associated with disease involving the small bowel and with penetrating or stricturing phenotype. Anti‐laminaribioside was significantly higher in patients with a familial history of inflammatory bowel disease. Conclusions: The new proposed serological markers are significantly associated with Crohns disease, with low sensitivity but good specificity. About one third of anti‐Saccharomyces‐negative patients may be positive for at least 1 of those markers. Antiglycan antibodies appear to be associated with characteristic localization and phenotype of the disease.

Prognostic implications of detection of troponin I in patients with unstable angina pectoris.

In our study, troponin I was not a predictor of cardiac events and a negative troponin I test did not exclude the presence of severe coronary artery disease. A positive troponin I test in patients with unstable angina identified a subgroup with probable, more active coronary disease (with higher levels of C-reactive protein).

Pluripotent plasticity of stem cells and liver repopulation

Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra‐hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self‐repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio‐artificial liver‐assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver. Copyright

Systemic high-dose recombinant-alpha-2a-interferon therapy modulates lymphokine production in multiple sclerosis

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

OXIDATIVE DAMAGE AND REPERFUSION SYNDROME IN HUMAN LIVER TRANSPLANTATION

In the transplanted organ, early after reperfusion, a consistent while usually transient tissue damage is detectable which could interfere with appropriate recovery and function. In the case of transplanted human liver, a certain degree of cytolysis as well as post-hepatic cholestasis have actually been monitored early after surgery (Ericzon et al., 1990; Biasi et al., 1995). Then, studies addressed to elucidate the mechanisms underlying post-transplantation liver injury are necessary. The inflammatory process which always follows a cytolytic event generates a variety of molecules actually able to modulate not only cellular function but also its genetic program. Hence, extent and duration of flogistic reactions should be controlled for not being overwhelming tissue and organ homeostasis.