Cytoskeleton Antibodies in Chronic Active Hepatitis, Primary Biliary Cirrhosis, and Alcoholic Liver Disease

Kurki, Pekka; Miettinen, Aaro; Salaspuro, Mikko; Virtanen, Ismo; Stenman, S

doi:10.1002/hep.1840030304

Cited by 56 publications

(4 citation statements)

References 25 publications

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“…Therefore, vimentin is commonly upregulated in the context of inflammation [18,[24][25][26]38]. Indeed, AVAs are also relatively common and have been reported in multiple states including rheumatoid arthritis [39], transplantation rejection [40][41][42], hepatitis, [43] pulmonary sarcoidosis [25], idiopathic pulmonary fibrosis [44], and infection (including acute viral hepatitis) [45]. We, propose that vimentin is a molecular pattern and potent antigen of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis

Kinloch

Cascino²,

Dai³

et al. 2020

Lupus

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Background Tubulointerstitial inflammation (TII) in lupus nephritis is associated with a worse prognosis. Vimentin, a filamental antigen, is commonly targeted by in situ activated B-cells in TII. The prognostic importance of high serum anti-vimentin antibodies (AVAs) in lupus nephritis and their relationship with common lupus autoantibody specificities is unknown. Herein we investigated associations between AVA isotypes, other autoantibodies, and response to mycophenolate mofetil (MMF) in the presence or absence of rituximab. Methods The Translational Research Initiative in the Department of Medicine (TRIDOM) cross-sectional cohort of 99 lupus patients was assayed for IgG-, IgA- and IgM- AVAs, lupus-associated and rheumatoid arthritis-associated antibodies, and hierarchically clustered. Serum from baseline, 26 and 52 weeks from 132 Lupus Nephritis Assessment with Rituximab (LUNAR) trial enrolled lupus nephritis patients was also analysed and correlated with renal function up to week 78. Results In TRIDOM, AVAs, especially IgM AVAs, clustered with IgG anti-dsDNA and away from anti-Sm and -RNP and rheumatoid arthritis-associated antibodies. In LUNAR at baseline, AVAs correlated weakly with anti-dsDNA and more strongly with anticardiolipin titers. Regardless of treatment, IgG-, but not IgM- or IgA-, AVAs were higher at week 52 than at baseline. In contrast, anti-dsDNA titers declined, regardless of therapeutic regime. High IgG AVA titers at entry predicted less response to therapy. Conclusion AVAs, especially IgG AVAs, are unique in distribution and response to therapy compared with other commonly measured autoantibody specificities. Furthermore, high-titer IgG AVAs identify lupus nephritis patients resistant to conventional therapies. These data suggest that AVAs represent an independent class of prognostic autoantibodies.

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Section: Discussionmentioning

confidence: 99%

Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis

Kinloch

Cascino²,

Dai³

et al. 2020

Lupus

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“…Antibodies to cytoskeleton components, including antibodies to intermediate filaments, have been described in chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease, with a high prevalence of antibodies of the IgA type in alcoholic liver disease (122,123). However, the mesenchymal cells used in the detection system contain vimentin intermediate filaments and no CK (122,123).…”

Section: Cks As Target Of Autoantibodies In Autoimmune Chronic Activementioning

confidence: 99%

Cytokeratins and the liver

Eyken

Desmet

1993

Liver

112

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“…-Sm, -Sc! 70, -dsDNA) defmed by immunodiffusion using extraetable nuclear antigens (calf thymus) and human spleen extract, and by Western blotting using a nuclear extract from HeLa cells [21]: (v)sera from palients with hepatitis A and C containing antibodies to laminin and keratin [22,23] but no other autoantibodies.…”

Section: H-+ -I--i-+ -I--t-mentioning

confidence: 99%

Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants

Lang

Klein

Becker

et al. 1992

Clinical and Experimental Immunology

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SUMMARYIn previous studies it was demonstrated that antibodies in sera from patients wilh primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2-and the naturally occurring mitochondrial antigen {NOMAg)-relatcd epitopes. Since separation of these two anligen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients wilh PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specificsera recognizing Ihe three major epitopes epsilon,zeta, and eta at 65.61 and 58 kD, Naturally occurring milochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast. the M2 antigen wa.s detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was losl in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2-and the NOMAg-relatcd epitopes could be only partially separated, i,e, there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies.

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Cytoskeleton Antibodies in Chronic Active Hepatitis, Primary Biliary Cirrhosis, and Alcoholic Liver Disease

Cited by 56 publications

References 25 publications

Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis

Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis

Cytokeratins and the liver

Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants

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