Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C

Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment. The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method. Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, γ-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2. In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.     

Stress hyperglycemia is predictive of worse outcome in patients with acute ischemic stroke undergoing intravenous thrombolysis

Journal of Thrombosis and Thrombolysis - No study investigated the possible detrimental effect of stress hyperglycemia on patients affected acute ischemic stroke (AIS) undergoing intravenous...     

Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of graves' ophthalmopathy.

Fifty-five patients with Graves' disease (GD) and mild to moderate Graves' ophthalmopathy (GO) underwent near-total thyroidectomy (Tx). In 16 patients this was followed by a standard ablative dose of (131)I because of the hystologic evidence of differentiated thyroid carcinoma. We retrospectively evaluated whether or not GO activity could be affected by thyroid surgery alone or followed by complete ablation of thyroid tissue. Accordingly, on the basis of clinical activity score (CAS) values prior to thyroidectomy, we identified two groups: group A with active GO (CAS > or = 3; n = 31) and group B with inactive GO (CAS < or = 2; n = 24). CAS values were then recorded at 6, 12, and 24 months after surgery/(131)I ablation. Over the course of the follow-up period, GO became inactive in approximately 70% of group A patients (CAS 4.2 +/- 0.8 at baseline, 2.1 +/- 2.0 at 24 months, p < 0.0001) and became active in 37.5% patients from group B. When we examined GO activity according to the type of treatment used (Tx or Tx and (131)I), the prevalence of inactive GO both short- and long-term, was significantly higher in the group of patients who underwent Tx and (131)I ablation. Therefore, this seems to be a more effective means of inducing and maintaining inactive GO.     

Proliferation of non-Hodgkin-lymphoma lymphocytes in vitro is dependent upon follicular dendritic cell interactions

Follicular dendritic cells (FDC) are located within the B-cell follicles of non-malignant lymphatic tissues and within non-Hodgkin-lymphomas (NHL) derived from the germinal centre or the mantlezone. The interactions between FDC and non-neoplastic B-cells have been extensively investigated but so far no data on functional studies with FDC isolated from lymphoma tissue are available. Using an enzyme cocktail to digest lymph nodes from patients with NHL followed by density centrifugation, single cell suspensions enriched in FDC and B-lymphocytes were obtained. In these preparations FDC formed small cellular clusters with an average of five neoplastic lymphocytes for every FDC. Immunocytochemistry with Ki67 revealed that after 24 h of culture 23.7% of the cells within the clusters were in late G1 to M phase. In contrast, only 10.2% of the lymphoma cells scattered outside the clusters were in these activated stages. As visualized by autoradiography, after 72 h of incubation the rate of proliferation was 16.8 times higher for the lymphoma cells involved in cluster formation as compared to those lymphocytes not associated with FDC. The data indicate that in vitro FDC from NHL lymph nodes form a microenvironment favourable for the activation and proliferation of lymphoma cells. The search for cytokines secreted by FDC in lymphoma tissue is under way.     

Differential gene expression and genomic patient stratification following left ventricular assist device support

OBJECTIVES: We sought to determine whether mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in significant changes in overall left ventricular gene expression. BACKGROUND: Mechanical circulatory support by LVAD in end-stage human heart failure (HF) can result in beneficial reverse remodeling of myocardial structure and function. The molecular mechanisms behind this salutary process are not well understood. METHODS: Left ventricular samples from six male patients were harvested during LVAD placement and subsequently at the time of explantation. Cardiac gene expression was determined using oligonucleotide microarrays. RESULTS: Paired t test analysis revealed numerous genes that were regulated in a statistically significant fashion, including the downregulation of several previously studied genes. Further statistical analysis revealed that the overall gene expression profiles could significantly distinguish pre- and post-LVAD status. Interestingly, the data also identified two distinct groups among the pre-LVAD failing hearts, in which there was blind segregation of patients based on HF etiology. In addition to the substantial divergence in genomic profiles for these two HF groups, there were significant differences in their corresponding LVAD-mediated regulation of gene expression. CONCLUSIONS: Support with an LVAD in HF induces significant changes in myocardial gene expression, as pre- and post-LVAD hearts demonstrate significantly distinct genomic footprints. Thus, reverse remodeling is associated with a specific pattern of gene expression. Moreover, we found that deoxyribonucleic acid microarray technology could distinguish, in a blind manner, patients with different HF etiologies. Expansion of this study and further development of these statistical methods may facilitate prognostic prediction of the individual patient response to LVAD support.     

Use of a monoclonal antibody against human heart ferritin for evaluating acidic ferritin concentration in human serum

Immunoassays for acidic ferritins rich in H subunits have shown that these isoferritins are predominant in some cells such as monocytes and red blood cells but have provided conflicting results about their presence in human serum. We have used an immunoradiometric assay based on a monoclonal antibody against human heart ferritin (monoclonal 2A4) for evaluating acidic ferritin concentration in human serum. This assay proved to be highly specific for acidic isoferritins having more than 60% H subunits. Heart-type ferritin was detected in only one fifth of normal sera and sera from patients with iron overload; values were very low compared with those for basic ferritin. Acidic ferritin was found in relatively high concentrations in most patients with iron deficiency anaemia. In other disease states characterized by increased serum concentrations of basic ferritin, acidic ferritin was always less than 21% of the total ferritin. Dialysis in low-ionic-strength buffer showed that both normal and pathological sera had binding factors for human heart ferritin. We conclude that: (i) human serum contains low concentrations of acidic isoferritins which, at variance with basic ferritin, do not appear to be directly related to the amount of storage iron; (ii) the findings of the present study reinforce the opinion that basic and acidic ferritins have different functional behaviours.