De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis

Abstract:  Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.     

The lacZ gene under the control of the 7 kb of human dystrophin muscle specific promoter is expressed in cardiac muscle but not in adult skeletal muscle in transgenic mice

In previous transgenic studies, we reported a 0.9 kb fragment from a mouse dystrophin muscle promoter that contains the regulatory elements required for expression of dystrophin only in the right heart. In this study, to further characterize the regulation of muscle type of promoter, we analyzed promoter activity and tissue specificity using a total 14 kb fragment around the human dystrophin muscular-specific exon 1 in vitro and in vivo. In vitro analysis showed that the lacZ construct of the 7 kb promoter and 7 kb intron 1 was expressed 2.5 times as strong as the lacZ construct of only the 7 kb promoter in C2/4 myotubes. In vivo analysis revealed expression of both constructs in the whole heart, skeletal muscle and vascular smooth muscle in embryos. However, in adults, the expression in skeletal muscle disappeared. We conclude that the 7 kb upstream region and the 7 kb intronic region included responsible elements for the expression in the heart, but not in skeletal muscle in vivo. It is possible that a strong enhancer element for skeletal muscle exists in some other region.     

Anti-carbonic anhydrase II antibody in autoimmune pancreatitis and tubulointerstitial nephritis

Nephrol Dial Transplant 2007; 22: 1273–1275;     

Quantitative phase analysis of myocardial wall thickening by technetium-99m 2-methoxy-isobutyl-isonitrile SPECT

Regional wall thickening was assessed by ECG-gated SPECT using technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI). For myocardial segments with an optimal short axis, regional count changes from end-diastole to end-systole were used to calculate the regional wall thickening. Functional images displaying amplitude, % wall thickening (% WT), and phase were generated by a fundamental Fourier analysis. In the control subjects, % WT analysis showed heterogeneous contraction among the left ventricular wall segments. The amplitude values showed a similar pattern to the %WT values. Phase images demonstrated that the timing of ventricular contraction was almost homogenous between the various wall segments. In the CAD patients, regional decreases in amplitude and %WT corresponding to zones of reduced perfusion were shown in the ischemic segments. Phase images also indicated asynchronous contraction in these segments. Phase analysis of regional wall thickening in 99mTc-MIBI scintigraphy seems to be useful for understanding regional myocardial function in combination with perfusion scanning.     

Lack of association between FCRL3 and FcgammaRII polymorphisms in Japanese type 1 autoimmune hepatitis

Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA-DRB1*0405 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. Recently, polymorphisms of Fcgamma receptors (FcgammaR) and Fc receptor-like gene 3 (FCRL3) were linked to a variety of autoimmune diseases, and may be at least partially responsible for susceptibility to AIH. In this study, we genotyped FcgammaRIIA, FcgammaRIIB, and four FCRL3 polymorphisms in 87 Japanese patients with type 1 AIH and 97 ethnically matched controls using the TaqMan assay. Although we were able to detect significantly lower serum IgG concentrations in AIH patients specifically with the FCRL3-110A/A genotype, we observed no difference in the distribution of the genotypes between patients and controls, implying that susceptibility to type 1 AIH in Japanese patients is not influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms.     

Endothelin(B) receptor blocker inhibits high glucose-induced synthesis of fibronectin in human peritoneal mesothelial cells.

BACKGROUND: Long-term peritoneal dialysis using glucose-based dialysates is associated with peritoneal fibrosis. The object of this study was to investigate the hypothesis that endothelin (ET)-1, which is known to play an important role in various fibrotic diseases, may also be involved in peritoneal fibrosis using human peritoneal mesothelial cells (HPMC). METHODS: HPMC were cultured with 4% D- or L-glucose, or loaded with 10 nmol/L ET-1. In some experiments, the ETA receptor antagonist BQ-123, the ETB receptor antagonist BQ-788, and antioxidants 4-hydroxy-2,2,6,6-tetramethyl-piperidine 1-oxyl (TEMPOL) and diphenyleneiodium chloride (DPI) were used. mRNA expression of ET-1, ETA receptor, ETB receptor, and fibronectin (FN) was analyzed by real-time polymerase chain reaction (real-time PCR). The protein levels for FN and ET-1 were measured by ELISA. CM-H2DCFDA-sensitive reactive oxygen species (ROS) were evaluated by flow cytometry. RESULTS: D-Glucose significantly induced mRNA expression of ET-1 and the ETB receptor but not the ETA receptor. FN production under high glucose conditions was inhibited by BQ-788. ET-1 directly stimulated H PMC to increase mRNA expression of FN and CM-H2DCFDA-sensitive ROS production. BQ-788, TEMPOL, and DPI inhibited mRNA expression of FN induced by ET-1. CONCLUSION: The present study suggests that high-glucose-induced FN synthesis is mediated by the ET-1/ETB receptor pathway and, therefore, an ETB receptor antagonist may be usefulin preventing FN production in HPMC.