0000000000304247
AUTHOR
Silvia Brunner
Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode.
Abstract Background/Aims: Antibodies to cytochrome P450 2D6, also knownas LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C. Methods: Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cy…
Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.
Summary Background Autoantibodies are a hallmark of autoimmune hepatitis, but most are not disease specific. Autoantibodies to soluble liver antigen (SLA) and to liver and pancreas antigen (LP) have been described as disease specific, occurring in about 30% of all patients with autoimmune hepatitis, but no standardised assays are available. Methods We tested 2000 serum samples from patients with various liver diseases and controls for SLA autoantibodies by inhibition ELISA. Serum samples positive for SLA antibodies were used for immunoscreening of cDNA expression libraries. Identified clones were tested against a panel of serum samples positive for SLA and LP autoantibodies and control seru…
Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro.
The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the …
Humoral Mechanisms in T cell Vaccination: Induction and Functional Characterization of Anti-lymphocytic Autoantibodies
T cell vaccination, the application of syngeneic attenuated T cells, has been shown to prevent effectively and treat experimental autoimmune diseases, but its mechanisms of action are poorly understood. Here we present data on the induction of a humoral anti-T cell response by T cell vaccination, capable of strongly inhibiting T cell proliferation and of ameliorating experimental autoimmune disease. T cell vaccination in the Lewis rat induced autoantibodies reactive with several syngeneic T cell proteins. These autoantibodies were not detectable in normal Lewis sera as assessed by immunoblotting and flow cytometry with intact syngeneic T cells. The autoantibody reactivity was not restricted…
Autoantibodies in experimental autoimmune hepatitis
Experimental autoimmune hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of autoimmune hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in autoimmune chronic active hepatitis patients. We conclude that autoantibodies arise…