Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.

CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes

CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia(CLL).Important functional properties are associated with CD5 expression in B cells,including signal transducer and activator of transcription 3 activation,IL-10 production and the promotion of B-lymphocyte survival and transformation.However,the pathway(s)by which CD5 influences the biology of B cells and its dependence on B-cell receptor(BCR)co-signaling remain unknown.In this study,we show that CD5 expression activates a number of important signaling pathways,including Erk1/2,leading to IL-10 production through a novel pathway independent of BCR engagement.This pathway is dependent on extracellular calcium(Ca2+)entry facilitated by upregulation of the transient receptor potential channel 1(TRPC1)protein.We also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 overexpression.In this subgroup of CLL patients,small inhibitory RNA(siRNA)for CD5 reduces TRPC1 expression.Furthermore,siRNAs for CD5 or for TRPC1 inhibit IL-10 production.These findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL.