Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis

Shimoda, Shinji; Nakamura, Minoru; Ishibashi, Hiromi; Kawano, Akira; Kamihira, Takashi; Sakamoto, Norihiro; Matsushita, Sho; Tanaka, Atsushi; Worman, Howard J.; Gershwin, M. Eric; Harada, Mine

doi:10.1016/s0016-5085(03)00387-1

Cited by 107 publications

(72 citation statements)

References 53 publications

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“…PDC-E2 [163][164][165][166][167][168][169][170][171][172][173][174][175][176] -specific CD4 þ Tcell clones also react with other AMA-specific mitochondrial autoantigens, including the E2 subunits of OGDC and BCOADC, as well as E3BP. 112,113 In all these molecules, interestingly, the epitopes include a lipoylated domain. The study of TCR b gene rearrangements of cell clones obtained from PBC liver biopsies demonstrated different degrees of oligoclonality of the infiltrating T cells.…”

Section: Immunopathogenesis Of Pbcmentioning

confidence: 99%

Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.

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Section: Immunopathogenesis Of Pbcmentioning

confidence: 99%

Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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“…Furthermore, auto-Abs found during the course of AID can also cross-react with different self-structures in the host. For example, anti-DNA auto-Ab from SLE patients can bind to α-laminin, α-actinin, myosin and the NR2 glutamate receptor (DeGiorgio et al 2001, Mageed & Zack 2002, and the "same" anti-DNA auto-Ab from primary biliary cirrhosis patients can cross-react with mitochondrial antigens (Shimoda et al 2003). In the same way, anti-cardiolipin (anti-M1) antibodies can bind to phospholipids and β 2 glycoprotein I (Harris & Pierangeli 1994).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

Brahimi

Martins

Zaniní

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…The pathogenic role of these antibodies, however, has been poorly investigated so far and remains unknown. 41 ) T-cell antigen receptor-ab 1 and CD8 1 T cells are most commonly seen in portal tracts, in particular around damaged bile ducts in the liver tissue of PBC patients, strongly suggesting the involvement of cellular immune mechanisms in biliary damage, [74][75][76][77][78][79][80][81] as suggested by liver tolerance. 82 In past decades, the nature and the role of cellular adaptive immune responses in PBC have been extensively characterized, showing that both CD4 and CD8 T cells participate in liver tissue damage.…”

Section: What Causes Liver Damage?mentioning

confidence: 99%