Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis

Background: Natural Killer T (NKT) cells are CD1d-restricted innate-like T cells that can rapidly release stored cytokines upon recognition of lipid antigens. In mice, type I NKT cells seem to promote liver inflammation, whereas type II NKT cells seem to restrict hepatitis. Here, we aimed at characterizing the role of human type I and type II NKT in patients with autoimmune hepatitis (AIH).Methods: NKT cells were analyzed by flow cytometry in peripheral blood and liver of AIH patients and control groups. α-galactosylceramide-loaded or sulfatide-loaded tetramers were used to detect type I or II NKT cells, respectively. Hepatic CD1d was stained by in situ-hybridization of liver biopsies.Results and Conclusions: Type II NKT cells were more prevalent in human peripheral blood and liver than type I NKT cells. In AIH patients, the frequency of sulfatide-reactive type II NKT cells was significantly increased in peripheral blood (0.11% of peripheral blood leukocytes) and liver (3.78% of intrahepatic leukocytes) compared to healthy individuals (0.05% and 1.82%) and patients with drug-induced liver injury (0.06% and 2.03%; p < 0.05). Intrahepatic type II NKT cells of AIH patients had a different cytokine profile than healthy subjects with an increased frequency of TNFα (77.8% vs. 59.1%, p < 0.05), decreased IFNγ (32.7% vs. 63.0%, p < 0.05) and a complete lack of IL-4 expressing cells (0% vs. 2.1%, p < 0.05). T cells in portal tracts expressed significantly more CD1d-RNA in AIH livers compared to controls. This study supports that in contrast to their assumed protective role in mice, human intrahepatic, sulfatide-reactive type II NKT cells displayed a proinflammatory cytokine profile in patients with AIH. Infiltrating T cells in portal areas of AIH patients overexpressed CD1d and could thereby activate type II NKT cells

Autoantibodies in Autoimmune Liver Disease—Clinical and Diagnostic Relevance

Testing for liver-related autoantibodies should be included in the workup of patients with hepatitis or cholestasis of unknown origin. Although most of these autoantibodies are not disease specific, their determination is a prerequisite to diagnose autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), and they are components of the diagnostic scoring system in these diseases. In primary sclerosing cholangitis (PSC), on the other hand, autoantibodies are frequently present but play a minor role in establishing the diagnosis. In PSC, however, data on antibodies suggest a link between disease pathogenesis and the intestinal microbiota. This review will focus on practical aspects of antibody testing in the three major autoimmune liver diseases AIH, PBC, and PSC

Autoantibodies in autoimmune liver disease—clinical and diagnostic relevance

Testing for liver-related autoantibodies should be included in the workup of patients with hepatitis or cholestasis of unknown origin. Although most of these autoantibodies are not disease specific, their determination is a prerequisite to diagnose autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), and they are components of the diagnostic scoring system in these diseases. In primary sclerosing cholangitis (PSC), on the other hand, autoantibodies are frequently present but play a minor role in establishing the diagnosis. In PSC, however, data on antibodies suggest a link between disease pathogenesis and the intestinal microbiota. This review will focus on practical aspects of antibody testing in the three major autoimmune liver diseases AIH, PBC, and PSC

Depression and anxiety in patients with different rare chronic diseases: A cross-sectional study.

ObjectiveEmpirical evidence on depression and anxiety in patients with rare diseases is scarce but can help improve comprehensive treatment. The objectives of this study were to investigate the frequency of depression and anxiety in this heterogeneous population and to examine aspects associated with increased psychopathology.MethodsN = 300 patients with 79 different rare diseases (female:80%, age:M = 44.3(12.8), range:16-74 years) participated in a cross-sectional online study. We determined the percentages of patients reporting elevated depression (PHQ-9) and anxiety (GAD-7) scores. We calculated two linear regressions with depression and anxiety as outcomes. Predictor variables were diagnosis-related aspects (diagnosis assigned to ICD-10 chapter, visibility of symptoms, time since diagnosis, comorbid diseases), perceived somatic-symptom-severity (PHQ-15), illness-perceptions (consequences, control, identity, concern, understanding and treatment control; B-IPQ-R), coping mechanisms (constructive attitudes, active engagement in life) and social support (heiQ). We controlled for gender, age and depression or anxiety depending on the outcome.Results42% of the patients (95%CI [36.41%,47.59%]) reported depression scores indicating moderately or severely elevated symptom levels. Regarding anxiety, this applies to 23% (95%CI [18.54%,28.06%]). Variables significantly associated with depression were higher perceived somatic-symptom-severity (B = 0.41,p ConclusionThe data reveal first insights into depression and anxiety in patients with different rare diseases. High percentages of patients showed clinically relevant symptom burden. No diagnosis-related differences were found in depression while anxiety seems to be particularly frequent in patients with rare diseases of the circulatory system. Besides perceived somatic symptom severity, cognitive appraisal seems to be linked to depression. Supporting patients in coping with their disease may help reduce psychopathology and therefore improve overall health

Autoantibodies to intracellular “rods and rings” structures in two patients with autoimmune hepatitis treated with azathioprine

In vitro, inhibition of the synthesis of guanosine monophosphate (GMP) by various drugs such as ribavirin, acyclovir, azathioprine, and mycophenolic acid leads to the formation of subcellular structures in cultured cells. Autoantibodies targeting these cellular structures can be detected as “rods and rings” (RR) patterns by immunofluorescence. In vivo, autoantibodies to RR have been almost exclusively associated with hepatitis C virus patients treated with pegylated interferon-α and ribavirin. However, longitudinal data for other patient groups are scarce. Here, we reviewed 276 sequential immunofluorescence results from 127 patients with autoimmune hepatitis for the presence of RR patterns. Of 102 patients exposed to drugs known to induce RR in vitro, two patients under long-term azathioprine therapy were positive for this pattern. This is the first report of anti-RR in patients with autoimmune hepatitis and in patients treated with azathioprine