Progressive renal failure and blindness due to retinal hemorrhage after interferon therapy for hepatitis C virus-associated membranoproliferative glomerulonephritis

We treated a 67-year-old Japanese woman with membranoproliferative glomerulonephritis (MPGN) and chronic active hepatitis associated with hepatitis C virus (HCV) infection. Treatment commenced with a daily dose of 6 MU IFN alpha-2b for 2 weeks, which was changed to three times weekly thereafter. After 2 weeks, HCV RNA in the serum was undetectable and there was a concomitant reduction in proteinuria. Treatment with IFN alpha-2b was discontinued because of severe headache and fever. Five weeks after the discontinuation of IFN alpha-2b, the patient experienced the sudden onset of visual loss due to retinal hemorrhage. Subsequently, proteinuria and renal function progressively deteriorated though HCV RNA was undetectable. This case exemplifies the need for careful monitoring of renal function and retinal lesions not only in patients receiving IFN but also in those following the discontinuation of IFN treatment.     

Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis

BACKGROUND AND AIMS: Serum antibodies to carbonic anhydrase (CA) II have been reported in patients with autoimmune pancreatitis (AIP) and Sjogren's syndrome (SjS). However, their significance in the pathogenesis of these diseases is controversial. The aim of this study was to identify serum antibodies to CA isozymes, which are expressed in ductal cells of the pancreas. METHODS: Recombinant proteins of human CAs IV, IX, and XII were obtained using a bacterial expression system, and five CA IV peptides with theoretically high antigenicity were synthesised. Western blotting and enzyme linked immunosorbent assay (ELISA) were used to detect serum antibodies to the CA isozymes. RESULTS: The first screening analysis by western blot showed serum antibodies to CA IV among three CA isozymes in patients with idiopathic chronic pancreatitis, including AIP patients. Further analysis by ELISA showed a significantly increased prevalence of serum antibodies to the truncated CA IV protein and the CA IV synthetic peptide (LGS LTT PTC DEK VVW TVF REP I) in patients with definite AIP (4/15 and 6/20, respectively; p<0.01), probable AIP (6/14 and 3/14; p<0.02), and SjS (9/20 and 8/40; p<0.001) compared with normal controls (0/26). There was no significant difference in the antibody prevalence rates between normal controls and patients with alcoholic chronic pancreatitis (2/15 in each) or pancreatic cancer (2/14 and 1/14, respectively). The presence of serum antibodies to the CA IV peptide showed significant correlations with serum gamma-globulin and IgG levels in AIP patients. CONCLUSIONS: These findings suggest that CA IV may be a target antigen that is commonly expressed in epithelial cells of specific tissues involved in AIP and its related diseases.     

Effect of GDF-5 and BMP-2 on the expression of tendo/ligamentogenesis-related markers in human PDL-derived cells

Oral Diseases (2012) 18 , 206–212 Objectives: The effect of growth differentiation factor 5 and bone morphogenetic protein 2 on human periodontal ligament‐derived cells was investigated with special reference to tendo/ligamentogenesis‐related markers. Materials and Methods: Effects of each factor were analyzed by quantitative PCR for scleraxis and tenomodulin and by western blotting for scleraxis. After exposure to those factors, STRO‐1‐positive and STRO‐1‐negative fractions of human periodontal ligament tissues were isolated with an immunomagnetic cell sorting system, and the expression of scleraxis in each fraction was analyzed by western blotting. Non‐separated crude cells were used as a control. Results: Growth differentiation factor 5 and bone morphogenetic protein 2 did not increase alkaline phosphatase activity in crude periodontal ligament‐derived cells. Growth differentiation factor 5, but not bone morphogenetic protein 2, increased the expression of scleraxis in crude, STRO‐1‐positive and STRO‐1‐negative periodontal ligament‐derived cells. The expression of scleraxis in STRO‐1‐positive periodontal ligament‐derived cells was significantly less compared to that in crude P2 and STRO‐1‐negative periodontal ligament‐derived cells. Conclusion: Growth differentiation factor 5 induced the expression of scleraxis and may enhance tendo/ligamentogenesis in human periodontal ligament‐derived cells. The expression of scleraxis was higher in STRO‐1‐negative fraction, suggesting more differentiated state of the cells.     

Effects of preceding sialadenitis on the development of autoimmunity against salivary gland

OBJECTIVE: The mechanism underlying the onset and development of autoimmune diseases such as Sjogren's syndrome is not well understood. Here, we examined the effects of preceding inflammation of the salivary gland at the onset of autoimmunity against the salivary gland. MATERIALS AND METHODS: One side of the submandibular gland duct was ligated in mice and the effect on the contralateral gland was investigated. After histological evaluation with hematoxylin and eosin staining, the presence of autoantibodies and immune compounds was examined. RESULTS: In all five strains of mice that were used, the salivary gland of the ligated side showed severe inflammation and atrophic change. In two mouse strains (SJL/J and PL/J), mild sialadenitis was observed on the non-ligated side 8 weeks after ligation. Autoantibodies reacting to the salivary gland were detected in three mouse strains (C3H/He, SJL/J, and PL/J). Immune complex was also detected in the duct basement membrane. CONCLUSION: The results indicate that the autoimmune mechanism is activated by the transient inflammation in the salivary gland under a specific genetic background.     

Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.